P bone remodeling with the initial pathologic event being. Cell Biology of Paget s Disease
|
|
- Vernon Doyle
- 5 years ago
- Views:
Transcription
1 JOURNAL OF BONE AND MINERAL RESEARCH Volume 14, Supplement 2, 1999 Blackwell Science, Inc. Q 1999 American Society for Bone and Mineral Research Cell Biology of Paget s Disease SAKAMURI V. REDDY, CHEIKH MENAA, FREDERICK R. SINGER: ANNE DEMULDER? and G. DAVID ROODMAN *4 ABSTRACT Paget s disease is characterized by markedly increased osteoclast formation and bone resorption followed by excessive new bone formation. Osteoclasts in Paget s disease are increased both in number and size, contain paramyxoviral-like nuclear inclusions, and can have up to 100 nuclei per cell. Marrow culture studies have identified several abnormalities in osteoclast formation in Paget s disease. Osteoclast-like multinucleated cells formed more rapidly in marrow cultures from patients with Paget s disease, produced increased levels of interleukin-6 0, and expressed high levels of IL-6 receptors compared to normals. IE6 levels were also increased in bone marrow and peripheral blood of patients with Paget s disease. In addition, osteoclast precursors from patients with Paget s disease are hyperresponsive to 1,25dihydroxyvitamin D3 (la(oh),d3) and calcitonin. The increased sensitivity of osteoclast precursors to 1,25(OH),D3 is mediated through the vitamin D receptor OR), since 24-hydroxylase activity is also up-regulated at concentrations of l,%(oh),d3 that are one log less than that needed to induce 24-hydroxylase activity in osteoclast precursors from normals. However, VDR numbers and affinity for l,e(oh),d3 do not differ in osteoclast precursors from Paget s patients compared to those from normals. Synergistic interactions between cytokines such as IL-6 and l,s(oh),d3 also cannot explain the enhanced sensitivity of osteoclast precursors from patients with Paget s disease to 1,25(OH),D3. Interestingly, coculture studies of osteoclast precursors and cells from the marrow microenvironment of patients with Paget s disease and normals have demonstrated that the marrow microenvironment is more osteoclastogenic than normal. Thus, studies of the cell biology of osteoclasts in Paget s disease have demonstrated an increased rate of osteoclast formation and abnormalities in both osteoclast precursors and the marrow microenvironment. Enhanced IL-6 praduction by osteoclasts in Paget s disease may further amplify the increased osteoclast formation already ongoing in the pagetic lesion, and may explain the increased bone turnover at uninvolved sites distant from the pagetic lesion. (J Bone Miner Res 1999,14, suppl. 2:M) INTRODUCTION AGET S DISEASE is characterized by grossly distorted P bone remodeling with the initial pathologic event being increased bone resorption.( * ) The greatly increased bone resorption is then followed by abundant new bone formation. The bone is rapidly laid down and is of poor quality. However, the primary cellular abnormality in Paget s disease is in the osteoclast rather than in the osteoblast. Osteoclasts from patients with Paget s disease have several distinct abnormalities that distinguish them from normal. In bone biopsy specimens of bone lesions from patients with Paget s disease, osteoclasts are markedly increased in number and size with the osteoclasts containing up to 100 nuclei per These osteoclasts appear to induce increased bone resorption, although the amount of resorption quantitated per osteoclast nuclei may actually be lower than that seen with normal o~teoclasts.(~) Ultrastructural studies of osteoclastic lesions from patients with Paget s disease have shown that they contain Department of MedicineMematology, University of Texas Health Science Center, San Antonio, Texas, U.S.A. 2John Wayne Cancer Center, Santa Monica, California, U.S.A. Brugmann Hospital, Brussels, Belgium. 4Audie Murphy Veterans Administration Hospital, San Antonio, Texas, U.S.A. 3
2 4 REDDY ET AL. paramyxoviral-like nuclear and cytoplasmic inclusion^,(^.^) and immunocytochemical studies have shown crossreactivity of these inclusions against measles virus nucleocapsid antibodies and respiratory syncytial virus nucleocap- sid antibodies, as well as other related paramyxo~iruses.(*.~) In situ hybridization studies on bone biopsy specimens from patients with Paget s disease have identified both measles virus transcripts and canine distemper virus transcripts in osteoclasts from patients with Paget s disease.( * ) Interestingly, other cells in the bone, in addition to osteoclasts, also express transcripts from measles virus or canine distemper virus (CDV) in these studies. In situ polymerase chain reaction studies have recently reported that 15 out of 15 bone biopsy specimens from patients with Paget s disease express canine distemper virus nucleocapsid messenger RNA, ) while osteoclasts from patients with osteoarthritis show no detectable viral sequences. However, the basis for the increased osteoclast formation and osteoclast activity in patients with Paget s disease has not been clearly defined. MATERIALS AND METHODS We have applied bone marrow culture techniques using bone marrow samples from bones affected with Paget s disease to try to unravel the underlying pathobiology of the osteoclasts in Paget s disease. In these studies, bone marrow was obtained from affected bones from patients with Paget s disease, then cultured in the presence of 1,25- dihydroxyvitamin D, (1,25(OH),D,) to induce osteoclastlike cell formation.( ) Multinucleated cells (MNC) that formed in these cultures expressed an osteoclast phenotype, that is, they reacted strongly with the 23c6 monoclonal antibody that identifies the osteoclast vitronectin re~eptor, ~) expressed tartrate-resistant acid phosphatase (TRAP) and calcitonin receptors, and formed resorption lacunae on calcified matrices.( 3) The osteoclasts formed in these cultures were markedly increased in number and size and had increased nuclear number, with up to 100 nuclei per cell. These MNC also expressed paramyxoviral antigens for measles virus and respiratory syncytial virus,(15) and shared ultrastructural features of osteoclasts isolated from patients with Paget s disease.(16) We have used these marrow culture techniques to examine osteoclasts and osteoclast precursors in Paget s patients. IL-6 and Paget s disease RESULTS An interesting feature of Paget s disease is that bones not clinically involved with the disease show increased bone remodeling.(17) Although several authors have suggested that the increased bone remodeling in bones not clinically involved with Paget s disease may be due to secondary hyperparathyr~idism,( ~~ ) increased parathyroid hormone (FTH) levels have not been consistently found in patients with Paget s disease, and the levels of PTH in Paget s patients in whom elevated PTH levels have been detected are not markedly increased. Therefore, we proposed that pagetic osteoclasts or other cells present in the bone lesions in patients with Paget s disease secreted a stimulatory factor that enhanced osteoclast formation and activity both within the lesion as well as at sites distant from the lesion. To test this hypothesis we obtained bone marrow from involved bones from patients with Paget s disease and cultured it with 1,25(OH),D, for 3 weeks to induce osteoclast formation. At the end of the culture period, the media was removed, serum-free media was added, and the cultures continued for 24 h. This Paget s conditioned media was then used as the only stimulatory factor in normal bone marrow cultures to induce osteoclast formation. Interestingly, when conditioned media from marrow cultures from patients with Paget s disease were used to stimulate osteoclast formation in normal marrow cultures, osteoclast formation was increased in a dose-dependent fashion between 5% and 25% v/v of the Paget s conditioned media. Higher concentrations were toxic to the cultures. In contrast, conditioned media obtained from marrow cultures from normals did not stimulate osteoclast formation under these conditions. We then wanted to identify the factor(s) present in the conditioned media from marrow cultures from patients with Paget s disease that was stimulating osteoclast formation in normal marrow cultures. Therefore, we added neutralizing antibodies to cytokines that were known to induce osteoclast formation, including interleukin-1 (IL-l), interleukin-6 (IL-6), transforming growth factor alpha (TGF-a), and granulocyte macrophage colony stimulating factor (GM-CSF) to normal marrow cultures stimulated with the Paget s conditioned media. ) We found that a neutralizing antibody to IL-6, but not to IL-1, tumor necrosis factor (TNF), or GM-CSF, completely blocked the osteoclast stimulatory activity present in the Paget s conditioned media. Bone marrow cultures contain mixed cell populations and it was unclear if stromal cells, macrophages, or the osteoclast-like cells formed in these marrow cultures from Paget s disease were the primary source for the IL-6 that was being produced. Therefore, we performed in situ hybridization studies to identify the cell types that expressed high levels of messenger RNA for IL-6. We found that the osteoclast-like cells were producing prodigious amounts of IL-6 messenger RNA. We then measured IL-6 levels in the conditioned media from both normal marrow cultures and marrow cultures from patients with Paget s disease and found that the patients with Paget s disease had significantly elevated IL-6 levels in this conditioned media compared to normals.(* ) However, it was unclear if these results were due simply to an in vitro phenomenon or reflective of what was occurring in patients with Paget s disease. Therefore, we obtained bone marrow aspirates and peripheral blood samples from patients with Paget s disease. The cells were separated immediately from the supernatants of the marrow aspirates and the peripheral blood samples after collection, and the supernatants from the marrow and the plasma from the peripheral blood were then tested by enzyme-linked immunosorbent assay (ELISA) for levels of IL-6. We found that
3 OSTEOCLASTS IN PAGET S DISEASE 5 IL-6 levels were markedly increased in the peripheral blood in 17 out of 21 patients with Paget s disease and in 9 out of 10 marrow samples from patients with Paget s disease compared to normals.(20) In fact, IL-6 levels up to 3 ng per ml were detectable in marrow supernatants from patients with Paget s disease, while IL-6 was essentially undetectable in both peripheral blood or marrow samples from normals. Consistent with our findings of IL-6 production by osteoclasts from Paget s patients are the findings of Hoyland and coworkers.(21) They performed in situ hybridization studies of bone biopsy specimens from patients with Paget s disease and patients with osteoarthritis or normal bone. These workers found that IL-6 nuclear factor, as well as IL-6 and IL-6 receptor messenger RNA, were markedly increased in osteoclasts from patients with Paget s disease compared to controls. They proposed that a paramyxoviral infection induces up-regulation of IL-6 and IL-6 receptor in osteoclasts from patients with Paget s disease, in that this IL-6 then acted in a paracrine fashion to stimulate osteoclast formation from osteoclast precursors. We have previously shown that IL-6 could stimulate normal osteoclast formation.( ) Consistent with this model for the up-regulation of IL-6 by paramyxovirus infection of osteoclasts are our preliminary findings in which, as a model for osteoclast precursors, we have infected normal peripheral blood monocytes with measles virus and shown that monocytes infected with measles virus express high levels of IL-6 and do not express to any significant degree other inflammatory cytokines such as IL-1 or TNF. Similarly, Mee et al.(lo) have shown that CDV infection of canine marrow cultures induces IL-6. Thus, IL-6 appears to be an autocrine/paracrine factor that may play an important role in amplifying the osteoclast formation in patients with Paget s disease, and may be responsible for the increased bone remodeling seen in bones not clinically involved with Paget s disease at sites distant from the pagetic lesion. Osteoclast precursors from Paget s patients are hyperresponsive to 1,25(OH),D, In our initial studies of bone marrow cultures from patients with Paget s disease, we found that osteoclast formation was markedly increased in these marrow cultures compared to those from normals, and osteoclast formation was increased as much as 20- to 100-fold above that seen in normal marrow cultures.( 3) Interestingly, the rate of osteoclast formation was also increased such that maximum osteoclast formation occurred within 2 weeks of initiation of these marrow cultures compared with 3 weeks in normal marrow cultures. Furthermore, we found that osteoclast formation in marrow cultures from patients with Paget s disease occurred with concentrations of 1,25(OH),D, that was at least one log less than that required for osteoclast formation in normal marrow cultures. Significant levels of osteoclast formation could be detected at concentrations at lo- M of 1,25(OH),D,, a concentration where no osteoclast formation occurred in normal marrow cultures. These data suggested that possibly there were intrinsic abnormalities in osteoclast precursors from patients with Paget s dis- ease compared to normal osteoclast precursors. Alternatively, these abnormalities in osteoclast formation and 1,25(OH),D, sensitivity could reflect intrinsic differences in the marrow microenvironment in Paget s disease, in particular, marrow stromal cells. To further determine if there were intrinsic abnormalities in osteoclast precursors from patients with Paget s disease or if abnormalities existed in the marrow microenvironment in pagetic lesions, we examined osteoclast precursors from Paget s patients and normals and compared their relative sensitivity to 1,25(OH),D, and to the marrow microenvironment. We had shown previously that the earliest identifiable osteoclast precursor is the granulocyte macrophage colony forming cell.(23) This cell then gives rise to an early osteoclast precursor that is bipotent and can form either monocyte-macrophages or differentiate further to form committed precursors for the osteoclasts. These committed precursors are unipotent and can only form osteoclasts. We isolated highly purified populations of both early and the committed osteoclast precursors and examined the capacity of highly purified populations of granulocytemacrophage colony-forming unit (CFU-GM) derived cells to form osteoclasts with varying concentrations of 1,25(OH),D,. Demulder and coworkers( ) demonstrated that early osteoclast precursors from patients with Paget s disease could form osteoclast-like cells in vitro with concentrations of 1,25(OH),D, that are at least one log less than that required for osteoclast formation by normal early osteoclast precursors. To confirm that these early osteoclast precursors from patients with Paget s disease were hyperresponsive to 1,25(OH),D,, 24-hydroxylase gene expression (the first gene product that is induced when 1,25(OH),D3 binds to VDR) was measured by reverse transcriptase polymerase chain reaction (RT-PCR). We found that 24-hydroxylase mrna expression could be detected in early precursors from patients with Paget s disease at concentrations of 1,25(OH),D, that are at least one to two logs less than that required for 24-hydroxylase expression by normal precursors. Increased sensitivity to 1,25(OH),D, could result from increased numbers of VDRs being expressed in early osteoclast precursors from patients with Paget s disease or an increased affinity of the VDR for 1,25(OH),D,. Therefore, we used RT-PCR to quantitate VDR expression in purified early osteoclast precursors from Paget s patients and normals. We found that the relative amount of VDR expressed by early precursors from Paget s patients was similar to that found with normals. Since all of these studies were done with RT-PCR, we then wanted to determine if VDR protein were being expressed in osteoclast-like cells formed in marrow cultures as well as by early osteoclast precursors and the more differentiated osteoclast precursors. We demonstrated by Western blot that osteoclast-like cells formed in vitro expressed VDR, and that both early and late osteoclast precursors expressed VDR. Interestingly, the amount of VDR expressed by osteoclast precursors decreases with osteoclast precursor differentiation. In collaboration with Dr. Barsony at the National Institutes of Health, Bethesda, MD, U.S.A., we measured the
4 6 REDDY ET AL. relative affinity of VDR for 1,25(OH),D, in osteoclast precursors from Paget s patients and normals using a fluoresceinated derivative of l,z(oh),d, and confocal microscopy.(25) We found that the relative affinity of VDR in early osteoclast precursors from Paget s patients was increased compared to normals. These data suggest that the increased sensitivity of osteoclast precursors from patients with Paget s disease was not due to increased numbers of VDRs but to increased affinity of VDR for 1,25(OH),D3, and that increased 1,25(OH),D, responsiveness was an intrinsic property of the osteoclast precursor. An alternative possibility that might explain the increased sensitivity of early osteoclast precursors from Paget s patients to 1,25(OH),D, was that cytokines made by these cells or by osteoclasts or stromal cells in the marrow microenvironment could enhance the sensitivity of these cells to 1,25(OH),D,. Since osteoclasts from patients with Paget s disease express IL-6, we tested if low levels of IL-6 could enhance the sensitivity of normal osteoclast precursors to 1,25(OH),D,. When normal bone marrow was cultured with varying concentrations of 1,25(OH),D, and 10 pg/ml of IL-6, the 1,25(OH),D3 dose-response curve for osteoclast formation was unchanged. Taken together, these data demonstrate that in patients with Paget s disease, enhanced sensitivity of osteoclast precursors to 1,25(OH),D3 is an intrinsic property of these cells. The enhanced sensitivity to 1,25(OH),D, is not due to interactions between other cytokines, nor is it due to abnormal numbers of VDR. The basis for the enhanced affinity of l,z(oh),d, for VDR in osteoclast precursors from patients with Paget s disease remains to be determined. Mee and coworkers have demonstrated that CDV infection of canine marrow cells increased their sensitivity to 1,25(OH),D,.( 0) Possibly, paramyxoviral infection of osteoclast precursors from Paget s patients may in part be responsible for their enhanced responsiveness to 1,25(OH),D,. Effects of the marrow microenvironment on osteoclast formation in patients with Paget s disease Another possible mechanism for increased osteoclast formation in patients with Paget s disease was that the marrow microenvironment may be abnormal. This seemed possible, since Paget s disease is a highly localized disease and patients do not develop new lesions throughout the course of their disease. We quantitated early osteoclast precursors (CFU-GM-derived cells) in bone marrow aspirates from involved bones from patients with Paget s disease or normals to determine if early osteoclast precursor numbers were increased. Demulder and coworkers( ) demonstrated that CFU-GM cells were significantly increased in marrow aspirates from patients with Paget s disease compared to normal. However, when these early osteoclast precursors were separated from marrow stromal cells using a monoclonal antibody against CD34 (an antigen that is expressed on hematopoietic precursors and not on stromal cells(26)) the number of osteoclast precursors present in normal marrow and marrow from patients with Paget s disease was very similar. Therefore, studies were performed using marrow stromal cells from normals and from patients with Pag- et s disease and cocultured with CD34-positive cells from normals or patients with Paget s disease, to determine if the stromal cells could enhance the growth of early osteoclast precursors. When normal CD3Cpositive cells were cocultured with normal stromal cells, the expected number of CFU-GM-derived colonies formed. However, when normal CD34-positive cells were cultured with stromal cells from patients with Paget s disease, there was a significant enhancement of CFU-GM growth; approximately 2-fold greater than the expected value. Similarly, when CD34- positive cells from Paget s patients were cocultured with stromal cells from Paget s patients, there was a 2.5-fold increase CFU-GM colony formation above the expected values. Interestingly, when CD34-positive cells from Paget s patients were cocultured with normal stromal cells, there again was enhanced growth of CFU-GM, to levels that were 2-fold above that expected. These data suggest that the marrow microenvironment from affected bones of patients with Paget s disease could enhance the growth of early osteoclast precursors, and that the early osteoclast precursors in patients with Paget s disease was hyperresponsive to the marrow microenvironment. To further dissect the abnormalities present in the marrow microenvironment from patients with Paget s disease compared to normal, marrow stromal cell lines were produced from normal marrow and marrow from patients with Paget s disease. Cell lines were produced by isolating CD34-negative cells, and then infecting these cells with a recombinant adenovirus which contains the SV40 large T antigen.( ) Both of these immortalized cell lines could support osteoclast formation, although the marrow stromal cell line from Paget s patients was more osteoclastogenic. These marrow stromal cell lines produced IL-6 and IL-1, which could enhance osteoclast formation. However, levels of RANK ligand mrna, a newly described stimulator of osteoclast formation which may be the common mediator for the effects of other osteoclastogenic factors on osteoclast formation,( ) was significantly elevated in the stromal cell line derived from patients with Paget s disease compared to that from normals. The enhanced expression of RANK ligand by stromal cells from patients with Paget s disease may explain in part the enhanced capacity of stromal cells from patients with Paget s disease to induce increased levels of osteoclast formation. DISCUSSION There are several abnormalities in osteoclast precursors as well as the marrow microenvironment in patients with Paget s disease (Fig. 1). Early osteoclast precursors are hyperresponsive to 1,25(OH),D3 and the marrow microenvironment. These cells appear to show enhanced growth even with the normal marrow microenvironment. In addition, these early osteoclast precursors contain measles virus nucleocapsid transcripts. The committed osteoclast precursors also contain measles virus nucleocapsid transcripts and appear to form osteoclasts at an increased rate compared to normal osteoclast precursors. The mature osteoclast formed in Paget s patients also contains measles virus tran-
5 OSTEOCLASTS IN PAGET S DISEASE 7 Model for Osteoclast Formation Macrophages Monocytes Hyper-responsive to: Micrmnvironment Abnormal Morphology CFU-Blast CFU-GM Early OCL Precursors Late OCL Precursors FIG. 1. Abnormalities in osteoclast precursors as well as the marrow microenvironment in patients with Paget s disease. scripts or canine distemper virus transcripts and produces prodigious amounts of IL-6, which can further amplify the increased osteoclast formation and activity in patients with Paget s disease. The marrow microenvironment also appears to be abnormal and has an enhanced capacity to induce osteoclast formation compared with the normal marrow microenvironment. The marrow stromal cells from patients with Paget s disease appear to demonstrate elevated levels of RANK ligand expression compared with normal marrow stromal cells. Thus, although the pathophysiology responsible for the increased osteoclast formation and activity in patients with Paget s disease is still beginning to be clarified, interesting and potentially important differences between osteoclast precursors from normals and patients with Paget s disease have been detected. ACKNOWLEDGMENTS This work was supported by Research Funds from the Veterans Administration and National Institutes of Health NIAMS Grants AR and AR 41336, NIADDK Grant AR 36125, and NCI Grant CA REFERENCES 1. Hosking DJ 1981 Paget s disease of bone. Br Med J 283:68& Yates AJ 1988 Paget s disease of bone. Baillieres Clin Endocrinol Metab Krane S 1986 Paget s disease of bone. Calcif Tissue Int 38: Rebel A, Basle M, Pouplard A, Kouyoumdjian S, Filmon R, LePatezour A 1980 Viral antigens in osteoclasts from Paget s disease of bone. Lancet Kanis JA 1991 Pathophysiology and Treatment of Paget s Dis- ease of Bone. Carolina Academic Press, Martin Dunitz, London, U.K. 6. Harvey L, Gray T, Beneton MNC, Douglas DL, Kanis JA, Russell RGG 1982 Ultrastructural features of the osteoclasts from Paget s disease of bone in relation to a viral aetiology. J Clin Pathol Rebel A, Malkani K, Basle M, Bregeon CH 1976 Osteoclast ultrastructure in Paget s disease. Calcif Tissue Res 24k Mills BG, Singer FR, Weiner LP, Suffin SC, Stabile E, Holst P 1984 Evidence for both respiratory syncytial virus and measles virus antigens in the osteoclasts of patients with Paget s disease of bone. Clin Orthop 183: Basle MF, Russell WC, Goswami KA, Rebel A, Giraudon P, Wild R, Filmon R 1985 Paramyxovirus antigens in osteoclasts from Paget s bone tissue detected by monoclonal antibodies. J Gen Virol66: Gordon MT, Mee AP, Anderson DC, Sharpe PT 1995 Canine bone marrow cultures infected with canine distemper virus: An in vitro model of Paget s disease. Bone Basle MF, Fournier JG, Rozenblatt S, Rebel A, Bouteille M 1986 Measles virus RNA detected in Paget s disease bone tissue by in situ hybridization. J Gen Virol Mee AP, Dixon JA, Hoyland JA, Davies M, Selby PL, Mawer EB 1998 Detection of canine distemper virus in 100% of Paget s disease samples by in situ-reverse transcriptase-polymerase chain reaction. Bone B Kukita A, Chenu C, McManus LM, Mundy GR, Roodman GD 1990 Atypical multinucleated cells form in long-term marrow cultures from patients with Paget s disease. J Clin Invest 85:128& Horton MA, Lewis D, McNulty K, Pringle JAS, Chambers TJ 1985 Monoclonal antibodies to osteoclastomas (giant cell bone tumors): Definition of osteoclast-specific cellular antigens. Cancer Res Mills BG, Frausto A, Singer FR, Ohsaki Y, Demulder A, Roodman GD 1994 Multinucleated cells formed in vitro from Paget s bone marrow express viral antigens. Bone Roodman GD, Ohsaki Y, Miller MM, Demulder A, Hosking D, Singer F, McManus L 1998 Pagetic osteoclasts formed in vitro: Absence of paracrystalline inclusions. J Submicrosc Cyto1 Pathol30:
6 8 REDDY ET AL. 17. Meunier PJ, Coindre JM, Edouard CM, Arlot ME 1980 Bone histomorphometry in Paget s disease. Arthritis Rheum U:lO Siris ES, Clemens TP, McMahon D, Gordon A, Jacobs TP, Canfield RE 1989 Parathyroid function in Paget s disease of bone. J Bone Miner Res & Reddy SV, Roodman GD 1998 Control of osteoclast differentiation. In: Stein GS, Stein JL, Lian JB (eds.) Critical Reviews in Eukaryotic Gene Expression. Begell House Inc, New York, pp Roodman GD, Kurihara N, Ohsaki Y, Kukita A, Hosking D, Demulder A, Singer FR 1992 Interleukin-4 A potential autocrine/paracrine factor in Paget s disease of bone. J Clin Invest 89: Hoyland JA, Freemont AJ, Sharpe IT 1994 Interleukin-6, IL-6 receptor, and IL-6 nuclear factor gene expression in Paget s disease. J Bone Miner Res Kurihara N, Bertolini D, Suda T, Akiyama Y, Roodman GD 1990 IL-6 stimulates osteoclast-like multinucleated cell formation in long-term human marrow cultures by inducing IL-1 release. J Immunol lm Kurihara N, Chenu C, Civin CI, Roodman GD 1990 Identification of committed mononuclear precursors for osteoclastlike cells formed in long-term marrow cultures. Endocrinology 126: Demulder A, Takahashi S, Singer FR, Hosking DJ, Roodman GD 1993 Evidence for abnormalities in osteoclast precursors and the marrow microenvironment in Paget s disease. Endocrinology Barsony J, Renyi I, McKoy W, Kang HC, Haugland RP, Smith CL 1995 Development of a biological active fluorescentlabeled calcitriol and its use to study hormone binding to the vitamin D receptor. Anal Biochem Civin CI, Banguenigo ML, Strauss LF, Loken MR 1987 Antigenic analysis of hematopoiesis. VI. Flow cytometric characterization of MY10 positive progenitor cells in normal human bone marrow. Exp Hematol Takahashi S, Reddy SV, Dallas M, Devlin R, Chou JY, Roodman GD 1995 Development and characterization of a human marrow stromal cell line that enhances osteoclast-like cell formation. Endocrinology 131k Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, Tomoyasu A, Yano K, Goto M, Murakami A, Tsuda E, Morinaga T, Higashio K, Udagawa N, Takahashi N, Suda T 1998 Osteoclast differentiation factor is a Ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCEIRANKL. Proc Natl Acad Sci USA Address reprint requests to: G. David Roodman, M.D., Ph.D. ResearcWHematology (151) 7400 Merton Minter Boulevard San Antonio, TX U.S.A. Received in original form March 15, 1999; in revised form May 15, 1999, accepted June 1,1999.
Atypical multinucleated cells form in long-term marrow cultures from patients with Paget's disease.
Atypical multinucleated cells form in long-term marrow cultures from patients with Paget's disease. A Kukita,, G R Mundy, G D Roodman J Clin Invest. 1990;85(4):1280-1286. https://doi.org/10.1172/jci114565.
More informationEnhanced RANK ligand expression and responsivity of bone marrow cells in Paget s disease of bone
Enhanced RANK ligand expression and responsivity of bone marrow cells in Paget s disease of bone Cheikh Menaa, 1 Sakamuri V. Reddy, 1 Noriyoshi Kurihara, 1 Hidefumi Maeda, 1 Dirk Anderson, 2 Tim Cundy,
More informationRegulation of Osteoclast Differentiation
Regulation of Osteoclast Differentiation G. DAVID ROODMAN University of Pittsburgh, School of Medicine/Hematology-Oncology, and VA Pittsburgh Healthcare System, Medicine/Hematology-Oncology, Pittsburgh,
More informationIRA-International Journal of Applied Sciences ISSN Vol. 03 Issue 02 (May, 2016) Paper DOI:
IRA-International Journal of Applied Sciences ISSN 2455-4499 Vol. 03 Issue 02 (May, 2016) Paper DOI: https://dx.doi.org/10.21013/jas.v3.n2.p8 Pathophysiology of Giant Cell Formation in Giant Cell Tumor
More informationEffect of corticosteroids on human osteoclast formation and activity
See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/11079968 Effect of corticosteroids on human osteoclast formation and activity Article in Journal
More informationDeposition of Bone by the Osteoblasts. Bone is continually being deposited by osteoblasts, and it is continually being resorbed where osteoclasts are
Bone remodeling Deposition of Bone by the Osteoblasts. Bone is continually being deposited by osteoblasts, and it is continually being resorbed where osteoclasts are active. This mechanism is always is
More informationsilent epidemic,. (WHO),
Tel: 02-740-8686; E-mail: hhbkim@snu.ac.kr silent epidemic,. (WHO),. 5 3, 1. 50 70. 50%, 25%, 20% (12~35%). 2.8% 0.7% 4. ( ). bone remodeling (osteoblast), (osteoclast),.. 3~4.. 70% (osteocyte) (bone lining
More informationConcise Review. Cytokines and Local Factors Which Affect Osteoclast Function. Bone Resorption Assays in Vitro. Introduction. Gregory R.
Concise Review International Journal of Cell Cloning 10:215-222 (1992) Cytokines and Local Factors Which Affect Osteoclast Function Gregory R. Mundy MedicineIEndocrinology, University of Texas Health Science
More informationMurine Pneumonia Virus: Seroepidemiological Evidence of Widespread Human Infection
J. gen. Virol. (1986), 67, 975-982. Printed in Great Britain 975 Key words: P VM/ Paget's bone disease/seroepidemiology Murine Pneumonia Virus: Seroepidemiological Evidence of Widespread Human Infection
More informationBone Health in Patients with Multiple Myeloma
Bone Health in Patients with Multiple Myeloma Amrita Y. Krishnan, MD Director Judy and Bernard Briskin Myeloma Center City of Hope Comprehensive Cancer Center Bone Health Bisphosphonates in Space Bone
More informationNew Agents for Myeloma Bone Disease
New Agents for Myeloma Bone Disease G. David Roodman MD PhD University of Pittsburgh Bone Remodeling is Uncoupled in Myeloma Normal Myeloma Hattner R et al. Nature. 1965;206:489. 1 Myeloma Bone Disease
More informationIndex. Index 439. Aequorin, 84, 94 Affinity precipitation, 372, AP-1, 100 Asthma, 170, 305
Index 439 Index A Aequorin, 84, 94 Affinity precipitation, 372, 376 381 AP-1, 100 Asthma, 170, 305 B Bioassay, 185, comparison with ELISA, 318 GM-CSF bioassay, 351 IL-2 bioassay, 185 192, 300 IL-3 IL-6
More informationBacteria Induce Osteoclastogenesis via an Osteoblast-Independent Pathway
INFECTION AND IMMUNITY, June 2002, p. 3143 3148 Vol. 70, No. 6 0019-9567/02/$04.00 0 DOI: 10.1128/IAI.70.6.3143 3148.2002 Copyright 2002, American Society for Microbiology. All Rights Reserved. Bacteria
More informationEffect of Interleukin 10 on the Hematopoietic Progenitor Cells from Patients with Aplastic Anemia
Effect of Interleukin 10 on the Hematopoietic Progenitor Cells from Patients with Aplastic Anemia YOSHINOBU ASANO, SHOICHIRO SHIBATA, SHINJI KOBAYASHI, SEIICHI OKAMURA, YOSHIYUKI NIHO First Department
More informationBone Cell Precursors and the Pathophysiology of Bone Loss
Bone Cell Precursors and the Pathophysiology of Bone Loss HARRY C. BLAIR, a AND JILL L. CARRINGTON b a Departments of Pathology and Cell Biology, University of Pittsburgh, and Pittsburgh VA Medical Center,
More informationPaget disease of bone
Bones THEME Paget disease of bone Diagnosis and indications for treatment BACKGROUND Paget disease was first described in 1877 by Sir James Paget. It is a focal disorder of bone remodelling, involving
More informationBone Cell Biology. David W. Dempster, PhD. Professor of Clinical Pathology Columbia University. Bone Remodeling
Bone Cell Biology David W. Dempster, PhD Professor of Clinical Pathology Columbia University Bone Remodeling The skeleton, out of site and often out of mind, is a formidable mass of tissue occupying about
More informationBone Cell Biology. The Remodeling Cycle. Bone Remodeling. Remodeling Maintains Mechanical Strength. David W. Dempster, PhD
Bone Remodeling Bone Cell Biology David W. Dempster, PhD Professor of Clinical Pathology Columbia University The skeleton, out of site and often out of mind, is a formidable mass of tissue occupying about
More informationUltrastructural features of the osteoclasts from
J Clin Pathol 1982;35:771-779 Ultrastructural features of the osteoclasts from Paget's disease of bone in relation to a viral aetiology L HARVEY, T GRAY, MNC BENETON, DL DOUGLAS,* JA KANIS,* RGG RUSSELL*
More informationGeneration of post-germinal centre myeloma plasma B cell.
Generation of post-germinal centre myeloma. DNA DAMAGE CXCR4 Homing to Lytic lesion activation CD38 CD138 CD56 Phenotypic markers Naive Secondary lymphoid organ Multiple myeloma is a malignancy of s caused
More informationOsteoclast-like Cells Form in Long-term Human Bone Marrow
Osteoclast-like Cells Form in Long-term Human Bone Marrow but not in Peripheral Blood Cultures N. Takahashi, T. Kukita, B. R. MacDonald,. Bird, G. R. Mundy, L. M. McManus,* M. Miller,*. Boyde,$ S. J. Jones,*
More informationThe pathogenesis of nervous distemper
Veterinary Sciences Tomorrow - 2004 The pathogenesis of nervous distemper Marc Vandevelde Canine distemper is a highly contagious viral disease of dogs and of all animals in the Canidae, Mustellidae and
More informationSredišnja medicinska knjižnica
Središnja medicinska knjižnica Kaštelan, D., Kaštelan, M., Prpić Massari, L., Koršić, M. (2006) Possible association of psoriasis and reduced bone mineral density due to increased TNF-alpha and IL-6 concentrations.
More informationBONE REMODELLING. Tim Arnett. University College London. Department of Anatomy and Developmental Biology
BONE REMODELLING Tim Arnett Department of Anatomy and Developmental Biology University College London The skeleton, out of sight and often out of mind, is a formidable mass of tissue occupying about 9%
More informationColony-stimulating Factors Regulate the Development of Multinucleated
Colony-stimulating Factors Regulate the Development of Multinucleated Osteoclasts from Recently Replicated Cells In Vitro Joseph A. Lorenzo, Sandra L. Sousa, Judith M. Fonseca, Janet M. Hock, and Eugene
More informationCONTRACTING ORGANIZATION: Medical University of South Carolina Charleston, SC 29425
AD Award Number: DAMD17-03-1-0763 TITLE: Measles Virus Nucleocapsid (MVNP) Gene Expression and RANK Receptor Signaling in Osteoclast Precursors, Osteoclast Inhibitors Peptide Therapy for Pagets Disease
More informationMcAb and rhil-2 activated bone marrow on the killing and purging of leukemia cells
Effects of McAb and rhil-2 activated bone marrow on the killing and purging of leukemia cells X.C. Wei, D.D. Yang, X.R. Han, Y.A. Zhao, Y.C. Li, L.J. Zhang and J.J. Wang Institute of hematological research,
More informationADx Bone Marrow Report. Patient Information Referring Physician Specimen Information
ADx Bone Marrow Report Patient Information Referring Physician Specimen Information Patient Name: Specimen: Bone Marrow Site: Left iliac Physician: Accession #: ID#: Reported: 08/19/2014 - CHRONIC MYELOGENOUS
More informationThe Pathogenesis of Bone Erosions in RA FULL VERSION
The Pathogenesis of Bone Erosions in RA FULL VERSION 1 Key Learning Objectives Understand the role of osteoclasts in normal bone remodeling Comprehend the key processes in pathologic osteoclast functions
More informationCYTOKINE RECEPTORS AND SIGNAL TRANSDUCTION
CYTOKINE RECEPTORS AND SIGNAL TRANSDUCTION What is Cytokine? Secreted popypeptide (protein) involved in cell-to-cell signaling. Acts in paracrine or autocrine fashion through specific cellular receptors.
More informationCD34+ Cells: A Comparison of Stem and Progenitor Cells in Cord Blood, Peripheral Blood, and the Bone Marrow
White Paper September 2016 CD34+ Cells: A Comparison of Stem and Progenitor Cells in Cord Blood, Peripheral Blood, and the Bone Marrow Lily C. Trajman, PhD Introduction: Hematopoietic Stem Cells (HSCs)
More informationReview Bone loss Factors that regulate osteoclast differentiation: an update Sophie Roux* and Philippe Orcel
http://arthritis-research.com/content/2/6/451 Review Bone loss Factors that regulate osteoclast differentiation: an update Sophie Roux* and Philippe Orcel * Lariboisière Hospital, Paris, and *Bicêtre Hospital,
More informationACTIVATION AND EFFECTOR FUNCTIONS OF CELL-MEDIATED IMMUNITY AND NK CELLS. Choompone Sakonwasun, MD (Hons), FRCPT
ACTIVATION AND EFFECTOR FUNCTIONS OF CELL-MEDIATED IMMUNITY AND NK CELLS Choompone Sakonwasun, MD (Hons), FRCPT Types of Adaptive Immunity Types of T Cell-mediated Immune Reactions CTLs = cytotoxic T lymphocytes
More informationTHE INFLUENCE OF SODIUM FLUORIDE ON THE CLONOGENECITY OF HUMAN HEMATOPOIETIC PROGENITOR CELLS: PRELIMINARY REPORT
168 Fluoride Vol. 33 No. 4 168-173 2 Research Report THE INFLUENCE OF SODIUM FLUORIDE ON THE CLONOGENECITY OF HUMAN HEMATOPOIETIC PROGENITOR CELLS: PRELIMINARY REPORT Boguslaw Machaliński, a Maria Zejmo,
More informationOsteoclast Activity Assay Substrate
Osteoclast Activity Assay Substrate For Research Use Only OSCOTECT INC. #3201 Trade Tower Samsung-dong 159, Kangnam-ku Seoul 135-729, Korea Tel: +82-2-6000-7666 / Fax: +82-2-6000-7667 customer@oscotec.com
More informationCYTOKINES. Based on: Cellular and Molecular Immunology, 4 th ed.,abbas A.K., Lichtman A.H. and Pober J.S. Sounders company; Philadelphia, 2010.
CYTOKINES Based on: Cellular and Molecular Immunology, 4 th ed.,abbas A.K., Lichtman A.H. and Pober J.S. Sounders company; Philadelphia, 2010. 1 What are cytokines? Glycoproteins (15 25 kda): Interleukins
More informationHepatitis B Antiviral Drug Development Multi-Marker Screening Assay
Hepatitis B Antiviral Drug Development Multi-Marker Screening Assay Background ImQuest BioSciences has developed and qualified a single-plate method to expedite the screening of antiviral agents against
More informationOsteoclasts- What Do They Do and How Do They Do It? Prof. Steven L. Teitelbaum
Osteoclasts; What Do They Do 1 Steven L. Teitelbaum, M.D. Wilma and Roswell Messing Professor Department of Pathology and Immunology Washington University School of Medicine OSTEOCLASTS OSTEOBLASTS 2 Osteoclasts
More informationGeneration of monocytederived Dendritic Cells (modcs)
monocytederived Dendritic (modcs) Application Note Background Dendritic (DCs) are so called because of their characteristic cell surface projections that resemble the dendrites of neurons (see Fig 1 and
More informationDifferentiation and function of osteoclasts. Takeshi Miyamoto and Toshio Suda
REVIEW Differentiation and function of osteoclasts Takeshi Miyamoto and Toshio Suda The Sakaguchi Laboratory of Developmental Biology, School of Medicine, Keio University, Tokyo, Japan (Received for publication
More informationChapter 13: Cytokines
Chapter 13: Cytokines Definition: secreted, low-molecular-weight proteins that regulate the nature, intensity and duration of the immune response by exerting a variety of effects on lymphocytes and/or
More informationIncreased osteoclastic activity in acute Charcot s osteoarthopathy: the role of receptor activator of nuclear factor-kappab ligand
Diabetologia (28) 51:135 1 DOI 1.17/s125-8-992-1 ARTICLE Increased osteoclastic activity in acute Charcot s osteoarthopathy: the role of receptor activator of nuclear factor-kappab ligand G. Mabilleau
More informationOsteoclast Culture Kit
K-ASSAY KAMIYA BIOMEDICAL COMPANY Osteoclast Culture Kit For the culture of Osteoclasts from precursor cells. Cat. No.: CC-107 Rat Osteoclast Precursor Cells, V-1 CC-109 Mouse Osteoclast Precursor Cells,
More informationChapter 7 Conclusions
VII-1 Chapter 7 Conclusions VII-2 The development of cell-based therapies ranging from well-established practices such as bone marrow transplant to next-generation strategies such as adoptive T-cell therapy
More informationAssessment and Treatment of Osteoporosis Professor T.Masud
Assessment and Treatment of Osteoporosis Professor T.Masud Nottingham University Hospitals NHS Trust University of Nottingham University of Derby University of Southern Denmark What is Osteoporosis? Osteoporosis
More informationQuantitative Determination of TNFá, a Multipotent Modulator of Immune Response
Quantitative Determination of TNFá, a Multipotent Modulator of Immune Response 1. Introduction Tumor Necrosis Factor á (TNFá), also known as cachectin, is a polypeptide cytokine produced by monocytes and
More informationRama Nada. - Mousa Al-Abbadi. 1 P a g e
- 1 - Rama Nada - - Mousa Al-Abbadi 1 P a g e Bones, Joints and Soft tissue tumors Before we start: the first 8 minutes was recalling to Dr.Mousa s duties, go over them in the slides. Wherever you see
More informationOsteoporosis and Inflammation Gregory R. Mundy, MD
December 2007(II): S147 S151 Osteoporosis and Inflammation Gregory R. Mundy, MD Osteoporosis represents a major healthcare burden, affecting approximately 10 million people aged over 50 years in the United
More informationIL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis
IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis Shigeru Kotake, 1 Nobuyuki Udagawa, 2 Naoyuki Takahashi, 2 Kenichiro Matsuzaki, 2 Kanami Itoh,
More informationMyelodysplastic Syndromes: Hematopathology. Analysis of SHIP1 as a potential biomarker of Disease Progression
Myelodysplastic Syndromes: Hematopathology. Analysis of SHIP1 as a potential biomarker of Disease Progression Carlos E. Bueso-Ramos, M.D., Ph.D Department of Hematopathology The University of Texas M.
More informationCytokines modulate the functional activities of individual cells and tissues both under normal and pathologic conditions Interleukins,
Cytokines http://highered.mcgraw-hill.com/sites/0072507470/student_view0/chapter22/animation the_immune_response.html Cytokines modulate the functional activities of individual cells and tissues both under
More information/01/$03.00/0 Endocrinology 142(8): Copyright 2001 by The Endocrine Society
0013-7227/01/$03.00/0 Endocrinology 142(8):3656 3662 Printed in U.S.A. Copyright 2001 by The Endocrine Society Bone Morphogenetic Protein 2 Stimulates Osteoclast Differentiation and Survival Supported
More informationOncolytic Immunotherapy: A Local and Systemic Antitumor Approach
Oncolytic Immunotherapy: A Local and Systemic Antitumor Approach Oncolytic immunotherapy Oncolytic immunotherapy the use of a genetically modified virus to attack tumors and induce a systemic immune response
More informationD.R.Haynes,T.N.Crotti,M.Loric,G.I.Bain 1,G.J.Atkins andd.m.findlay 1
Rheumatology 2001;40:623±630 Osteoprotegerin and receptor activator of nuclear factor kappab ligand RANKL) regulate osteoclast formation by cells in the human rheumatoid arthritic joint D.R.Haynes,T.N.Crotti,M.Loric,G.I.Bain
More informationVitamin D: Is it a superhero??
Vitamin D: Is it a superhero?? Dr. Ashraf Abdel Basset Bakr Prof. of Pediatrics 1 2 History of vitamin D discovery Sources of vitamin D and its metabolism 13 Actions of vitamin D 4 Vitamin D deficiency
More informationChapter 4. Estrogen receptor expression in human macrophages
Chapter 4 Estrogen receptor expression in human macrophages 4.1. Introduction Macrophages respond to estrogen present in their microenvironment and hence should express functional estrogen receptors unless
More informationHematopoiesis. BHS Liège 27/1/2012. Dr Sonet Anne UCL Mont-Godinne
Hematopoiesis BHS Liège 27/1/2012 Dr Sonet Anne UCL Mont-Godinne Hematopoiesis: definition = all the phenomenons to produce blood cells Leukocytes = White Blood Cells Polynuclear = Granulocytes Platelet
More informationPaget's disease, bone
Postgrad MedJ 1997; 73: 69-74 The Fellowship of Postgraduate Medicine, 1997 Classic diseases revisited Summary Paget's disease of bone is a relatively common condition in the UK affecting up to 5% of the
More informationSUPPLEMENTARY INFORMATION
1. Supplementary Figures and Legends Supplementary Fig. 1. S1P-mediated transcriptional regulation of integrins expressed in OP/monocytoid cells. Real-time quantitative PCR analyses of mrna for two integrins,
More informationCytokines and Growth Factors
Cytokines and Growth Factors Cytokines are a category of signalling proteins and glycoproteins that, like hormones and neurotransmitters, are used extensively in cellular communication. While hormones
More informationQuestion 1. Kupffer cells, microglial cells and osteoclasts are all examples of what type of immune system cell?
Abbas Chapter 2: Sarah Spriet February 8, 2015 Question 1. Kupffer cells, microglial cells and osteoclasts are all examples of what type of immune system cell? a. Dendritic cells b. Macrophages c. Monocytes
More informationExpression of Osteoprotegerin and RANK Ligand in Breast Cancer Bone Metastasis
J Korean Med Sci 2003; 18: 541-6 ISSN 1011-8934 Copyright The Korean Academy of Medical Sciences Expression of Osteoprotegerin and RANK Ligand in Breast Cancer Bone Metastasis Bone destruction is primarily
More informationPART FOUR. Metabolism and Nutrition
PART FOUR Metabolism and Nutrition Advances in Peritoneal Dialysis, Vol. 21, 2005 Maria Mesquita, 1 Eric Wittersheim, 2 Anne Demulder, 2 Max Dratwa, 1 Pierre Bergmann 3 Bone Cytokines and Renal Osteodystrophy
More information/00/$03.00/0 Vol. 141, No. 9. Osteoprotegerin Produced by Osteoblasts Is an Important Regulator in Osteoclast Development and Function*
0013-7227/00/$03.00/0 Vol. 141, No. 9 Endocrinology Printed in U.S.A. Copyright 2000 by The Endocrine Society Osteoprotegerin Produced by Osteoblasts Is an Important Regulator in Osteoclast Development
More informationOsteoclast Culture Kit
K-ASSAY Osteoclast Culture Kit For the culture of Osteoclasts from precursor cells. Cat. No.: CC-107 Rat Osteoclast Precursor Cells, V-1 For Research Use Only. 1 Rev. 091708 K-ASSAY PRODUCT INFORMATION
More informationOsteoclast: Origin and Differentiation
1. Osteoclast: Origin and Differentiation Janet Rubin and Edward M. Greenfield Introduction The skeleton is an engineering feat: it is strong but light enough to permit locomotion, rigid to allow muscles
More informationInterleukin-l Production in Patients with Nonlymphocytic Leukemia and Myelodysplastic Syndromes
Interleukin-l Production in Patients with Nonlymphocytic Leukemia and Myelodysplastic Syndromes N. J. Simbirtseva 1 A common feature of all cases of myeloid leukemia is a block in normal maturation of
More informationLaboratory Diagnosis of Viral Infections. G. Jamjoom 2005
Laboratory Diagnosis of Viral Infections G. Jamjoom 2005 Five Main Techniques: Virus Culture and Isolation Serology Rapid Detection of Viral Antigens Detection of Viral Nucleic Acid Electron Microscopy
More informationNature Medicine: doi: /nm.2109
HIV 1 Infects Multipotent Progenitor Cells Causing Cell Death and Establishing Latent Cellular Reservoirs Christoph C. Carter, Adewunmi Onafuwa Nuga, Lucy A. M c Namara, James Riddell IV, Dale Bixby, Michael
More informationBone Health in the Cancer Patient. Stavroula Otis, M.D. Primary Care and Oncology: Practical Lessons Conference Brea Community Center May 10, 2018
Bone Health in the Cancer Patient Stavroula Otis, M.D. Primary Care and Oncology: Practical Lessons Conference Brea Community Center May 10, 2018 Overview Healthy bone is in a constant state of remodelling
More informationProstate Cancer 2009 MDV Anti-Angiogenesis. Anti-androgen Radiotherapy Surgery Androgen Deprivation Therapy. Docetaxel/Epothilone
Prostate Cancer 2009 Anti-Angiogenesis MDV 3100 Anti-androgen Radiotherapy Surgery Androgen Deprivation Therapy Docetaxel/Epothilone Abiraterone DC therapy Bisphosphonates Denosumab Secondary Hormonal
More informationA novel role for vitamin D: modulation of expression and function of the local renin angiotensin system in mouse pancreatic islets
Diabetologia () 5:77 DOI.7/s5--- SHORT COMMUNICATION A novel role for vitamin D: modulation of expression and function of the local renin angiotensin system in mouse pancreatic islets Q. Cheng & Y. C.
More informationDisruption of Rankl/Rank Signaling Reduces TNF-Induced Joint Inflammation
The Open Arthritis Journal, 9,, 7-13 7 Open Access Disruption of Rankl/Rank Signaling Reduces -Induced Joint Inflammation In Vivo Zhenqiang Yao 1, Ping Li, Qian Zhang 1, Ruolin Guo 1, Edward M. Schwarz,
More informationInternational Journal of Cell Cloning (1991)
Concise Review International Journal of Cell Cloning 9542-547 (1991) Hybrid Cytokines as Hematopoietic Growth Factors Douglas E. Williamsa, Linda S. Park", Hal E. Broxmeyerb, Li Lub 'Immunex Research and
More informationIndex. Note: Page numbers of article titles are in boldface type.
Note: Page numbers of article titles are in boldface type. A Adaptive immune response biologic response modifiers and, 735 737 S-Adenosylmethionine (SAMe) for hepatitis, 825 826 Albinterferon for hepatitis,
More informationEffects of Anti RANK ligand Denosumab on Beta Thalassemia induced osteoporosis
Effects of Anti RANK ligand Denosumab on Beta Thalassemia induced osteoporosis Mohamed Yassin 1 Ashraf T. Soliman2, Mohamed O. Abdelrahman3, Vincenzo De Sanctis 4 Departments of, 1 Hematology 2Pediatric
More informationTitle: NATURAL KILLER CELL FUNCTIONS AND SURFACE RECEPTORS
LECTURE: 14 Title: NATURAL KILLER CELL FUNCTIONS AND SURFACE RECEPTORS LEARNING OBJECTIVES: The student should be able to: Describe the general morphology of the NK-cells. Enumerate the different functions
More informationOsteoclast-like giant cells (GCs) are postulated to derive
Giant Cell Tumors Inquiry Into Immunohistochemical Expression of CD11 (c-kit), Microphthalmia Transcription Factor, Tartrate-Resistant Acid Phosphatase, and HAM-56 Rolando Y. Ramos, MD; Helen M. Haupt,
More informationTITLE: Breast Tumor-Generated Type 1 Collagen Breakdown Fragments Act as Matrikines to Drive Osteolysis
AD Award Number: W81XWH-08-1-0639 TITLE: Breast Tumor-Generated Type 1 Collagen Breakdown Fragments Act as Matrikines to Drive Osteolysis PRINCIPAL INVESTIGATOR: Ching Hua William Wu PhD. CONTRACTING ORGANIZATION:
More informationChronic Myeloid Leukemia Outlook: The Future of CML Therapy
Chronic Myeloid Leukemia Outlook: The Future of CML Therapy Neil Shah, MD PhD Edward S. AgenoDistinguished Professor in Hematology/Oncology UCSF School of Medicine San Francisco, California Progression
More informationDNA vaccine, peripheral T-cell tolerance modulation 185
Subject Index Airway hyperresponsiveness (AHR) animal models 41 43 asthma inhibition 45 overview 41 mast cell modulation of T-cells 62 64 respiratory tolerance 40, 41 Tregs inhibition role 44 respiratory
More informationSpace radiation and osteoclastogenesis:the effects of radiation and microgravity on bone resorption:
Space radiation and osteoclastogenesis:the effects of radiation and microgravity on bone resorption: Alamelu Sundaresan1, Sukesh Aghara2, Terrell Gibson1and Indi Siripirasan2 1: Texas Southern University-3100
More informationBasis of Immunology and
Basis of Immunology and Immunophysiopathology of Infectious Diseases Jointly organized by Institut Pasteur in Ho Chi Minh City and Institut Pasteur with kind support from ANRS & Université Pierre et Marie
More information(25(OH)D3), 61%; 24,25-dihydroxycholecalciferol, 29%; cholecalciferol,
HIGHLY SPECIFIC BINDING OF 1,25-DIHYDROXYCHOLECALCIFEROL IN BONE CYTOSOL S. C. MANOLAGAS, C. M. TAYLOR AND D. C. ANDERSON Department of Medicine, University of Manchester School of Medicine, Manchester
More informationDiagnostic Tests for HIV
Mountain West AIDS Education and Training Center Diagnostic Tests for HIV David Spach, MD Principal Investigator, Mountain West AETC Professor of Medicine, University of Washington Last Updated: June 22,
More informationCytokines, adhesion molecules and apoptosis markers. A comprehensive product line for human and veterinary ELISAs
Cytokines, adhesion molecules and apoptosis markers A comprehensive product line for human and veterinary ELISAs IBL International s cytokine product line... is extremely comprehensive. The assays are
More informationulation of NK cells that retain the capability of expressing the HNK-1 differentiation antigen. Children with the Chediak-Higashi (CH)' syndrome,
RAPID PUBLICATIONS Natural Killer (HNK-1l) Cells in Chediak-Higashi Patients Are Present in Numbers but Are Abnormal in Function and Morphology TORu ABO, JOHN C. RODER, WATARU ABO, MAX D. COOPER, and CHARLES
More informationMutation in Osteoactivin Enhances RANKL-Mediated Signaling, Promoting Osteoclast Differentiation, Survival and Inhibiting Bone Resorption
Mutation in Osteoactivin Enhances RANKL-Mediated Signaling, Promoting Osteoclast Differentiation, Survival and Inhibiting Bone Resorption Samir Abdelmagid, MD, PhD, Fouad Moussa, BS, Sondag Gregory, MS,
More informationBone Remodelling And Its Disorders By Gregory R Mundy
Bone Remodelling And Its Disorders By Gregory R Mundy If you are searched for a book Bone Remodelling and its Disorders by Gregory R Mundy in pdf format, then you have come on to the loyal website. We
More informationPhilip Osdoby 1,2. Metabolism, Washington University Medical School, St. Louis, MO 63110, and 3 Department of
JBC Papers in Press. Published on March 23, 2001 as Manuscript M010153200 RANKL and OPG expression by human microvascular endothelial cells, regulation by inflammatory cytokines, and role in human osteoclastogenesis
More informationMAINTAINANCE OF skeletal integrity requires a dynamic. Perspective
JOURNAL OF BONE AND MINERAL RESEARCH Volume 15, Number 1, 2000 2000 American Society for Bone and Mineral Research Perspective The Roles of Osteoprotegerin and Osteoprotegerin Ligand in the Paracrine Regulation
More informationPresenter: 翁家嫻 Venue date:
FOR THE TREATMENT OF OSTEOPOROSIS IN POSTMENOPAUSAL WOMEN AT INCREASED RISK OF FRACTURES 1 Presenter: 翁家嫻 Venue date: 2018.03.13 PMO: postmenopausal osteoporosis. 1. Prolia (denosumab), Summary of Product
More informationExtensive osteolysis adjacent to implants is often
The osteoclastogenic molecules RANKL and RANK are associated with periprosthetic osteolysis D. R. Haynes, T. N. Crotti, A. E. Potter, M. Loric G. J. Atkins, D. W. Howie, D. M. Findlay From the University
More informationSilent Killer: Osteoporosis
Special Dedication to the Old Females Silent Killer: Osteoporosis David Goltzman, Discoveries, Drugs and Skeletal Disorders Nature, Volume 1, October 2002, pp784-796 BII Journal Club Wang Zhengyuan 5:00-5:30pm
More informationIdentification of mirna differentially expressed in macrophages exposed to Porphyromonas gingivalis infection
Boston University OpenBU http://open.bu.edu Graduate Research Symposium Graduate Research Symposium 216 216-4-1 Identification of mirna differentially expressed in macrophages exposed to Porphyromonas
More informationBisphosphonates in the Management of. Myeloma Bone Disease
Bisphosphonates in the Management of Myeloma Bone Disease James R. Berenson, MD Medical & Scientific Director Institute for Myeloma & Bone Cancer Research Los Angeles, CA Myeloma Bone Disease Myeloma cells
More informationTumor Associated Macrophages as a Novel Target for Cancer Therapy
Tumor mass Tumor Associated Macrophage Tumor Associated Macrophages as a Novel Target for Cancer Therapy This booklet contains forward-looking statements that are based on Amgen s current expectations
More informationDoctor of Philosophy
Regulation of Gene Expression of the 25-Hydroxyvitamin D la-hydroxylase (CYP27BI) Promoter: Study of A Transgenic Mouse Model Ivanka Hendrix School of Molecular and Biomedical Science The University of
More informationSunitinib, an orally available receptor tyrosine kinase inhibitor, induces monocytic
Sunitinib, an orally available receptor tyrosine kinase inhibitor, induces monocytic differentiation of acute myeogenouse leukemia cells that is enhanced by 1,25-dihydroxyviatmin D 3. To the Editor: Sunitinib,
More information