Original Article. Abstract. Utari Kresnoadi, Maretaningtias Dwi Ariani, Eha Djulaeha, Nike Hendrijantini

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1 Originl Artile The potentil of mngosteen (Grini mngostn) peel extrt, omine with eminerlize freeze rie ovine one xenogrft, to reue rige resorption n lveolr one regenertion in preserving the tooth extrtion soket Utri Kresnoi, Mretningtis Dwi Arini, Eh Djuleh, Nike Henrijntini Deprtment of Prosthoontis, Fulty of Dentl Meiine, Airlngg University, Sury, Inonesi Astrt Bkgroun: Following the extrtion of tooth, one resorption n use signifint prolems for susequent enture implnt n restortive entistry. Thus, the tooth extrtion soket nees to e mintine to reue the hne of ny lveolr rige one resorption. Ojetive: The ojetive of this stuy is to etermine whether the ministrtion of mngosteen peel extrts (MPEs), omine with eminerlize freeze rie ovine one xenogrft (DFBBX) mterils for tooth extrtion soket preservtion, oul potentilly reue inflmmtion y erese the expression of nuler ftor κβ (NfK) n reeptor tivtor of nuler ftor κβ lign (RANKL), to inhiit lveolr one resorption, n inrese of one morphogeneti protein 2 (BMP2) expressions to elerte lveolr one regenertion. Mterils n Methos: This stuy onsists of severl stges. First, osge of MPE omine with grft mterils ws pplie to preserve tooth extrtion soket of Cvi oy. Seon, the C. oy ws exmine using immune histohemil expression of NfK, RANKL, BMP2, s well s histology of osteolsts n osteolsts. The reserh ws sttistilly nlyze, using n nlysis of vrine test n Tukey honest signifint ifferene test. Results: The results of this reserh were tht it ws etermine tht MPEs omine with grft mterils on preserve tooth extrtion soket n reue NfK, RANK, n osteolsts lso inrese of BMP2 n osteolst. Conlusion: The inution of MPEs n DFBBX is effetive in reuing inflmmtion, lowering osteolsts, eresing lveolr one resorption, n lso inresing BMP2 expression n lveolr one regenertion. Keywors: Bone morphogeneti protein 2, grft mterils, mngosteen peel extrts, nuler ftor κβ, preserve tooth extrtion soket, reeptor tivtor of nuler ftor κβ lign expressions Aress for orresponene: Prof. Utri Kresnoi, Deprtment of Prosthoontis, Fulty of Dentistry, Airlngg University, Jln Myjen, Prof. Dr. Moestopo No. 47 Sury 60132, Est Jv, Inonesi. E mil: ut.kres@yhoo.om Reeive: 07 th Mrh, 2017, Aepte: 19 th My, 2017 Quik Response Coe: Aess this rtile online Wesite: ips.org DOI: /jips.jips_64_17 This is n open ess rtile istriute uner the terms of the Cretive Commons Attriution NonCommeril ShreAlike 3.0 Liense, whih llows others to remix, twek, n uil upon the work non ommerilly, s long s the uthor is reite n the new retions re liense uner the ientil terms. For reprints ontt: reprints@meknow.om How to ite this rtile: Kresnoi U, Arini MD, Djuleh E, Henrijntini N. The potentil of mngosteen (Grini mngostn) peel extrt, omine with eminerlize freeze-rie ovine one xenogrft, to reue rige resorption n lveolr one regenertion in preserving the tooth extrtion soket. J Inin Prosthoont So 2017;17: The Journl of Inin Prosthoonti Soiety Pulishe y Wolters Kluwer - Meknow

2 INTRODUCTION The posttooth extrtion one resorption proess n result in signifint prolems for enture implnts n restortive entistry. To eter the enture from flling prt, one of the most importnt ftors in enture onstrution is its retention ftor, whih is hevily ffete y other ntomil ftors, suh s high sling rige s ntilever for the enture implnt. To gin high positionl rige, the rige resorption, usully use y trum fter tooth extrtion, nees to e reue. Inflmmtion will trigger osteolst growth n lso use lveolr one resorption. Originl tooth extrtion soket preservtion in ptients is require to reue the likelihoo of ourrene of lveolr one resorption. Conservtion of the originl tooth extrtion soket in ptients, long with n optiml tehnique of entl implnt therpy is neee. The sme prinipl n e pplie to the eentulous re, to inrese the estheti point on oth fixe n removle entures. [1] Inflmmtion n rise the numer of osteolst ells, pro inflmmtion ytokines (tumor nerosis ftor (TNF) α n interleukin 1 β (IL 1 β), n lso reeptor tivtor of nuler ftor κβ lign (RANKL) n RANK (reeptor tivtor of nuler ftor κβ). [2,3] The RANKL proess is signl of n osteolst, whih ours euse the TNF or TNF reeptor fmily plys n importnt role in ontrolling the eth of ells n lso the prolifertion of ells. Fmily moleule RANK n RANKL reeptors re key regultors of one remoeling n re essentil for osteolst tivtion n evelopment. [4] When osteolst ell growth rises, lveolr one resorption will tke ple. Hyen, et l. [5] hve stte tht nuler ftor κβ (NfK) is one spet of the use of inflmmtion. The pro inflmmtion ytokine proution pth inites speifi epeneny on NfK, just s TNF α tivtes NfK; therefore, NfK is funmentl prt of propgtion n ytokine response. Aoring to Bellnti, [6] the level of inflmmtion n e tegorize s ute, su ute, or hroni. Aute inflmmtion tkes ple from the 1 st y until the thir; susequently, there will e hroni inflmmtion, se on the history of illness. In the fiels of Meiine n Dentistry, the use of grfts to men or ugment one efet is ommon prtie, [7 12] ut it ws not stle enough to proue the expete result. In the one growth proess, one morphogeneti protein 2 (BMP2) triggers the proess of osteolst genesis, stimulting either n osteolsti speifi ftor 2 or ore ining ftor 1, ffeting the proue osteolst; the ollgen 1 n nonollgen prout osteolin will inrese, n nother lveolr one growth will pper. [13] Deminerlize freeze rie ovine one xenogrft (DFDBBX) is prout me y Btn Reserh Tissue Bnk n offere in power form; it hs een relieve of its immunogeni ttriute y gmm (γ) ry rition. There re vrious uses for mngosteen peel in the meil fiel, one of them eing s n nti inflmmtory; it my lso funtion s n ntioxint, n is lso ple of tivting woun heling hormones. [14] Perz Chverri, et l., [14] Plkwong, et l., [15] Khirunis, [16] Ytmn, [17] stte in their report tht xnthones were etete insie the mngosteen peel n tht these ontin ienzopyrn, n nti inflmmtory sustne. Dienzofurn is lose reltive to the flvonois n nother nti inflmmtory whih works y inhiiting the proution of the ylooxygense 2 (COX 2) enzyme, the min use of inflmmtion. Vrious illnesses re use y free rils; in proteting the oy from free rils, the ntioxint sustne stilizes them. Mngosteen peels ontin ompouns tht re useful s ntioxints n re lso phrmologilly tive: flvonoi, xntone, n tnnin. [18] Bse on the ove esription, the question rises s to whether the ministrtion of omintion of mngosteen peel extrt (MPE) n DFDBBX on tooth extrtion sokets n erese the genertion of NfK, RANKL s n initor of inflmmtion, reuing osteolsts, lowering the hne of rige resorption n lso inresing BMP2 expression n lveolr one regenertion. This reserh is n effort t tissue engineering, with the ojetive of preserving tooth extrtion sokets y omining MPE n DFDBBX to fill in the extrtion soket to reue the inflmmtion use y the extrtion, whih n use rige resorption n inrese osteolst ells, resulting in lveolr one regenertion. MATERIALS AND METHODS Reserh proeure n niml moel Every proeure performe in this reserh meets the ethil requirements s stte y the Dentistry Ethis Commission of Airlngg University s stipulte in their eree No 1/KKEPK.FKG/III/2015. The mterils use re mngosteen (Gri mngostn) peel extrt, sterile istille wter (ques), DFDBBX, solute lohol, 70% lohol, monolonl ntioy nti NfK p 56 (Snt Cruz), monolonl ntioy RANKL (Snt Cruz), monolonl ntioy BMP2 (Snt Cruz), immune stining kit regent (Novostr Lei), n regent The Journl of Inin Prosthoonti Soiety Volume 17 Issue 3 July-Septemer

3 for hemtoxylin n eosin (HE) oloring. Iniret immunohistohemilly exmintion n e onute using primry ntioies s well s seonry ntioies. The experimentl nimls use were helthy n tive mle Cvi oy (Guine pigs), weighing roun g, ge months. RANKL, n BMP2 expressions, n lso Osteolst n Osteolst ells, ws rrie out uner light mirosope eh slie ws exmine with 1000 times mgnifition n mximum of 10 fiels of view. The lultion results were note on worksheet with men vlue per fiel of view. The MPE ws otine using mertion tehnique; fter tht the most pproprite osge of the mixture of MPE n xenogrft + polyethylene glyol (PEG) ws lulte, followe y Histopthologi Exmintion of Osteolsts n Osteolsts y HE, long with stining n immunohistohemistry exmintion using monolonl ntioy NfK p 56, RANKL, n BMP2. Reserh proeure Fifty six C. oys were ivie into eight groups, eh group ontining seven nimls. The groups were then seprte into 7 y groups n 30 y groups, eh group reeive four tretments. The tooth extrte ws the ottom right inisor. Afterwr, the C. oy were tken from their tretment fility n nesthetize intrvenously with 0.2 CC/300 g ketmine BB. [19] The ottom left inisor extrtion ws onute with speilize (neele holer) pliers. The extrtion soket ws then fille with PEG, DFDBBX + PEG, MPE + PEG, n omintion of MPE + DFDBBX + PEG. Eh mixture ws llowe s muh s 0.1 CC, orresponing with the volume of the tooth extrtion soket, whih ws then sewn up with Brun Aesulp rn polymie monofilment sewing thre, DS 12 3/8, 12 mm, 6/10 met, 0.7 sterile. [20] The groups ws sorte s follows. Groups 1 n 2: Tooth extrtion performe, followe y filling in the soket with PEG only. Groups 3 n 4: Tooth extrtion performe followe y filling in the soket using DFDBBX + PEG. Groups 5 n 6: Tooth extrtion ws performe, followe y filling in the soket with MPE n PEG. Groups 7 n 8: Tooth extrtion ws performe followe y filling in the soket with omintion of MPE + DFDBBX + PEG. An exmintion fter 7 n 30 ys for eh group were onute. Histopthologi speimen preprtion After 7 ys n 30 ys h psse, the C. oys were euthnize n their jws were remove with surgil inision. Prffin lok ws prepre. The prffin lok ws then slie, using rotry mirotome with thikness of pproximtely 4 µ, fter whih it ws li out on glss slie. Deprffiniztion ws onute y issolving the speimen in xylol for 2 3 min. The reminer of the xylol ws wshe out with solute lohol, 99%, 95%, 90%, 80%, 70%, for 2 1 min eh, the lultion for NfkB, The lultion results were then reore n tulte to e sttistilly nlyze y the Kolmogorov Smirnov metho n homogeneity test. An An nlysis of vrine (ANOVA) ws onute to isern the ifferenes mong the groups. A multiple omprison y Tukey honest signifint ifferene (HSD) ws then rrie out, to isover the group with the est result. RESULTS The preliminry results for the est osge, numer of lulte men n stnr evitions (SDs) of osteolsts n osteolsts fter 30 ys of tretment, showe tht the ose of 2% h the highest osteolst result t The lowest osteolst ount ourre in the ontrol group tht ws only fille with PEG, i.e., , while the highest osteolst ount ws oserve from the ose ontrol with result of ; menwhile, the ose of 2% otine the lowest yiel t 7. The osteolst n osteolst lultion results with 2% osge n with tretment for 7 n 30 ys re presente in Figure 1. The lok igrm [Figure 1] isplys the ifferene etween the ontrol groups, the DFDBBX + PEG, the MPE + PEG, n the MPE + DFDBBX + PEG group. The group tht ws trete with MPE + DFDBBX + PEG h the highest osteolst numer, t ± SD Figure 1: Men of osteolst n osteolst, xis X: Aount of osteolst n osteolst. Axis Y: tretment fille soket with PEG (ontrol), DFDBBX + PEG (Grft), MPE + PEG n omintion of MPE + DFDBBX + PEG t 7 n 30 ys. PEG: Polyethylene glyol, DFDBBX: Deminerlize freeze rie ovine one xenogrft, MPE: Mngosteen peel extrt 284 The Journl of Inin Prosthoonti Soiety Volume 17 Issue 3 July-Septemer 2017

4 Menwhile, the lowest osteolst ount ws in the ontrol group. Aginst this, for osteolsts, the lowest numer ws the preise group with MPE + DFDBBX + PEG with vlue of 8.50 ± SD 1.761, while the highest osteolst numer ws in the ontrol group (or PEG only group) with vlue of SD ± 3. A mirosopi pperne of osteolsts n osteolsts n e seen in Figure 2. From the normlity test, we otin P = < 0.05, the result showing tht there re signifint ifferenes etween the groups. On the Levene test, homogeneity test whih ws rrie out efore the ANOVA test otine P = > 0.05, whih mens tht we n ontinue with the ANOVA test. The ANOVA sttistil test on the 7 n 30 ys tretment shows signifint ifferene of the osteolsts n osteolsts on the ontrol group, the DFDBBX + PEG group, the MPE + PEG group, n the MPE + DFDBBX + PEG omintion group, hrterize y signifine vlue of 0.00 < There re signifint ifferenes etween Osteolst ells in the ontrol group n in the MPE group, n lso in the MPE n DFDBBX omintion group with P = < Menwhile, the results of the ANOVA sttistil test on osteolst ells for the 7 n 30 ys tretment re s follows: results show signifint ifferenes of the osteolst ells etween ontrol group, DFDBBX + OEG group, MPE Group, n MPE + DFDBBX + PEG omintion group, inite y P = 0.00 < This ws then followe y sttistil Tukey HSD test for osteolst ells, with the results initing signifint ifferenes etween osteolst ells in the ontrol group, n the MPE group, n lso the MPE + DFDBBX + PEG omintion group with P = < There re lso ifferenes etween the ontrol group n DFDBBX (Xenogrft) group with P = < The result of the immunohistohemistry test or NfK, RANKL, BMP2, osteolst n osteolst with 2% osge on the 7 n 30 ys tretments is s follows [Figure 3]. The ifferene for expression group NfK p 65 n e seen strting from the ontrol group, DFDBBX + PEG group, MPE + PEG group, n MPE + DFDBBX + PEG group. The lowest sore elongs to the MPE + DFDBBX + PEG with 5.44 ± SB Menwhile, the highest sore elongs to the ontrol group (the PEG only group) with ± SB The ifferenes re visile in the mount of RANKL expression in the ontrol group, DFDBBX + PEG group, MPE + PEG group, n MPE + DFDBBX + PEG omintion group. The lowest sore elongs to the MPE + DFDBBX + PEG omintion group whih is 5.17 ± SB 1472, while the highest sore elongs to the ontrol group (PEG only group) whih is ± SB As for the osteolst, the highest sore elongs to the ontrol group (PEG only group) with SB ± 3. In the BMP2 expression exmintion, the highest sore elonge to the MPE + DFDBBX + PEG omintion with (30 ys) n the lowest elonge to the ontrol group (PEG only) group with 3.14 (30 ys). An overview of NfK, RANKL n BMP2 expression on 30 ys exmintion n e seen in Figures 4 6. Figure 2: Figure Mirosopi of osteolst n osteolts t 30 ys. (). Fille soket with PEG; (). Fille soket with DFDBBX + PEG; (). Fille soket with Mnggosteen peel extrt + PEG; (). Fille soket with omintion of Mngosteen peel extrt + DFDBBX + PEG. Blk rrow show Osteolst. White rrow show Osteolst Figure 3: Osteolst, osteolst, RANKL, NfK, n BMP2 t 7 ys n 30 ys. Axis X: Aount of Osteolst, osteolts, expression of RANKL, NfK, n BMP2. Axis Y: Tretment fille soket with PEG (ontrol), DFBBX + PEG (grft), MPEs + PEG n omintion MPE + DFBBX + PEG t 7 n 30 ys. RANKL: Reeptor tivtor of nuler ftor κβ lign, NfK: Nuler ftor κβ, BMP2: Bone morphogeneti protein 2, PEG: Polyethylene glyol, MPE: Mngosteen peel extrt, DFBBX: Deminerlize freeze rie ovine one xenogrft The Journl of Inin Prosthoonti Soiety Volume 17 Issue 3 July-Septemer

5 Figure 4: Mirosopi figure of expression of RANKL t 30 ys. () Fille with PEG; () fille with DFDBBX + PEG; () fille with MPE + PEG; () fille with omintion of MPE + DFDBBX + PEG. Blk rrow show RANKL expression. RANKL: Reeptor tivtor of nuler ftor κβ lign, DFDBBX: Deminerlize freeze rie ovine one xenogrft, MPE: Mngosteen peel extrt, PEG: Poly etylene glyol ANOVA sttistil lultions on NfK expression on the 7 n 30 ys tretments show signifint ifferenes of the NfK results on the ontrol group, DFBBX + PEG group, MPE + PEG group, n MPE + DFBBX + PEG omintion group, s inite y signifint vlues of P = 0.00 < 0.05 on 7 n 30 ys tretments. This ws then followe y Tukey HSD Sttistil test on the NfK expression results, whih showe signifint ifferenes of the NfK expression for the 7 n 30 ys tretments etween the ontrol group n MPE group, with vlue of P = < Furthermore, etween the ontrol group n MPE + DFBBX + PEG omintion group, with vlue of P = < ANOVA sttistil lultions of RANKL expression on the 7 n 30 ys tretments show signifint ifferenes on the RANKL expression results on the ontrol group, DFDBBX + PEG group, MPE + PEG group, n MPE + DFDBBX + PEG omintion group, s inite y signifint vlue of P = 0.00 < This ws then followe y Tukey HSD Sttistil test on RANKL expression results, whih showe signifint ifferenes of the RANKL expression for the 7 n 30 ys tretments etween the ontrol group n MPE group, with vlue of P = < Furthermore, the ontrol group n MPE + DFDBBX + PEG omintion group with vlue of P = < There is lso signifint ifferene etween ontrol groups n DFDBBX + PEG groups, with vlue of P = < A eline in the numer of osteolst ells for the mount of NfK n RANKL expression ourre in Figure 5: Mirosopi figure of NfK expression t 30 ys. () Fille with PEG; () fille with DFDBBX + PEG; () fille with MPE + PEG; () fille with omintion of MPE + DFDBBX + PEG. Blk rrow shows NfK expression. NfK: Nuler ftor κβ, DFDBBX: Deminerlize freeze rie ovine one xenogrft, MPE: Mngosteen peel extrt, PEG: Poly etylene glyol every group on the 7 ys tretment, from the ontrol group, the DFBBX group, the MPE group, n the MPE + DFBBX + PEG group. The lowest eline ws oserve on the MPE group + DFBBX + PEG group. DISCUSSION Trum resulting from the extrtion of teeth n use inflmmtion; oring to Yenry et l., [21] when trum ours, the immunoompetent mrophge ells n mst ells will inrese the TNF α (pro inflmmtory ytokines). As prt of the immune response is ontrolle y NfK whih ontins ytosol n is oun to Ikpp B (IkB), this will le to IkB phosphoryltion, whih then uses protesome egrtion n relese of NfK from the trnslotion into the nuleus. Even though the inflmmtion from extrtion trum hs susie, n the extrtion woun is lose, the mstition proess in the orl vity woul use mehnil stimuli to e iretly epte y resiul rige through the neurogeni reeptor, whih will tivte the TNF α n IL 1. This woul men tht even when the extrtion woun hs lose, the lveolr one resorption will ontinue to our. [20] There hs een istintion in this stuy on the lok igrm of NfK expression for the ontrol group, DFBBX + PEG group, MPE + PEG group, n the MPE + DFBBX + PEG group. This stuy shows tht stuffing/filling the tooth extrtion soket with omintion of MPE + DFBBX + PEG ws effetive in reuing the NfK n RANKL expression signifintly; this is in orne with stuy y Chen et l., [22] whih stte tht Grin mngostn Linn n e use s n nti inflmmtory. The types of Xnthone known to e the 286 The Journl of Inin Prosthoonti Soiety Volume 17 Issue 3 July-Septemer 2017

6 Figure 6: Mirosopi figure of BMP2 expression t 30 ys. () Fille soket with PEG; () fille soket with DFDBBX + PEG; () Fille soket with mngosteen peel extrt + PEG; () fille with omintion of mngosteen peel extrt + DFDBBX + PEG. Blk rrow show BMP2 expression. BMP2: Bone morphogeneti protein 2, DFDBBX: Deminerlize freeze rie ovine one xenogrft, PEG: Poly etylene glyol most enefiil re the α mngostin n γ mngostin. Both of these re quite ple of inhiiting the proution of nitri oxie n PGE2 from liposhri ell stimultion RAW In the humn oy, Xnthone serves s n ntioxint, ntiprolifertive, nti inflmmtory, n nti miroil. Xnthone is strong ntioxint whih is extremely importnt in the lning of pro oxints in the oy, lso known s free rils in our nturl surrounings. [16] Aoring to Nktni et l., [23] γ mngostin possesses the ility to inhiit the proution of the enzyme COX, the use of inflmmtion, n iretly retrs the tivity of IkB kinse enzyme, while lso preventing COX 2 gene trnsription (NfK trget genes), s well s suppressing the proution of PGE2 in the inflmmtory proess. This stuy is in orne with stuy y Jinsrt, et l. [24] whih sttes tht in the mngosteen peel there re xnthones, whih ontin n nti inflmmtory: The α n γ mngostin, whih is the min iotive ompoun. In this stuy, the lok igrm of the RANKL expression result shows the ifferenes mong eh group, from the ontrol group, DFDBBX + PEG group, MPE + PEG group, n MPE + DFBBX + PEG omintion group. It shows tht the omintion of MPE + DFDBBX + PEG proues the lowest RANKL expression; it inites tht there is signifint erese of inflmmtion euse of the preservtion of the tooth extrtion soket y filling it with MPE + DFBBX + PEG. This is in orne with nother stuy from Porth n Mtfin [25] whih sttes tht inflmmtion will use mrophges to inue pro inflmmtory syntheti ytokines IL 1 n TNF α, whih ply role in the relese of phospholipis from the firolst ell memrne, ell mst, neutrophil, mrophge, n lymphoytes; hene, the phospholipse A2 enzyme my strt working s rhioni i metolism initites n proues the COX 2 enzyme. An inrese in the level of COX 2 plys role in the synthesis of prostglnins, espeilly PGE 2 sine it n use n inrese in vsoilttion n n inrese enothelil permeility, therey filitting the infiltrtion of inflmmtory ells. [26] RANKL is key meitor of the osteolst evelopment proess The RANKL ining to the RANK reeptor on the preosteolst surfe will tivte the jun terminl kinse n NfK, whih les to osteolst evelopment. [26] RANKL lso plys n importnt role in osteoimmunology. When COX 2 is inhiite n the pro inflmmtory ytokines (IL 1, TNF α) n lso PGE 2 eline, osteolst evelopment, either iretly or through RANKL, will e hmpere, so ifferentition n fusion of osteolst preursors into osteolsts will not our. Asie from tht, inhiition my lso our in the ouning proess of the RANKL to RANK on the surfe of preosteolsts whih will hmper the tivtion of NfK; where the NfK les to osteolst evelopment, eresing NfK will reue the osteolst ell numers. [27] Soket preservtion proeure ims to reue the loss of one following tooth extrtion, to mintin the lveolr one volume. This is rrie out y pling one grft into the extrtion soket immeitely fter the tooth is extrte. [28] There hs een n inrese in the numer of BMP2 expressions, the highest numer eing with the insertion of MPE + DFDBBX + PEG omintion; the BMP2 is n lveolr one growth ftor, n it shows in the inresing numer of osteolst ells. In orne with stuy y Pgni, et l., [29] BMP is growth ftor; it n inue ifferentition of stem ells into ells tht will evelop the one, in proess lle osteoinution. A stuy one introue metho to preserve the soket fter tooth extrtion proess y utilizing the BMP2 sore in sponge ollgen. This ws one y Howell, et l. in 1997, whih shows tht this BMP2 grfting mteril is sfe; the result of the preservtion on the ptient shows n inrese of lveolr one mteril. The result of this stuy shown in the lok igrm mkes it ler tht the lowest osteolst ount is oserve in the MPE + DFDBBX + PEG group, while the highest osteolst ount elongs to the ontrol group. From this stuy, we n onlue tht utilizing the omintions of MPE with DFDBBX n PEG s filling/stuffing prove The Journl of Inin Prosthoonti Soiety Volume 17 Issue 3 July-Septemer

7 effetive in eresing NfK n RANKL expression, whih then le to erese in inflmmtion, reuing osteolst ell growth n rige resorption. This reserh lso provies n insight into the proess of homeostsis in ones, tht when the osteolst ells responsile for rige resorption erese [30] then osteolst ells s one forming elements will rise. CONCLUSION The onlusion of this reserh is the inution of omintion of MPEs n DFDBBX is effetive in reuing inflmmtion, lowering osteolsts, eresing lveolr one resorption, n lso inresing BMP2 expression n lveolr one regenertion. Aknowlegments We woul like to thnk the Retor of Airlngg University who provie us with the leing reserh grnt for universities No. 519/UN3/2015, te Mrh 26, 2015, from the Ministry of Reserh, Tehnology n Higher Eution, through the Institute of Reserh n Innovtion t Airlngg University. Finnil support n sponsorship This stuy ws supporte y Airlngg University. Conflits of interest There re no onflits of interest. REFERENCES 1. Dry I, Chen S, De Poi R. 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Alveolr rige preservtion utilizing the soket plug tehnique. Int J Orl Implntol Clin Res 2012;3: Pgni G, Pellegrini G, Ginnoile WV, Rsperini G. Postextrtion lveolr rige preservtion: Biologil sis n tretments. Int J Dent 2012;2012: Roomn GD. Regultion of osteolst ifferentition. Ann N Y A Si 2006;1068: The Journl of Inin Prosthoonti Soiety Volume 17 Issue 3 July-Septemer 2017