Lecture 2: Skeletogenesis

Transcription

1 Jilin University School of Stomatology Skeletogenesis Lecture 2: Skeletogenesis Aug. 18, 2015 Yuji Mishina, Ph.D.

2 Student will describe Development of Bone - the general anatomy of bone and cartilage at the organ and tissue level - the stages/steps of endochondral and intramembranous bone development - the concept of coupling and how bone is remodeled and maintained during homeostatsis

3 Four Major Functions of the Skeleton Support: Forms the frame work that supports the body and cradles soft organs Mineral Storage: Reservoir for minerals specially calcium and phosphorus Protection: Provide a protective case for the brain, spinal chord, and vital organs like the heart and lungs Housing for bone marrow: Hematopoiesis occur and mesenchymal stem cells reside within the marrow cavaties of bone

4 Student will describe Development of Bone - the general anatomy of bone and cartilage at the organ and tissue level - the stages/steps of endochondral and intramembranous bone development - the concept of coupling and how bone is remodeled and maintained during homeostatsis

5 BASIC OSTEOLOGY Axial skeleton (support & protection) Skull & mandible Vertebrae (including sacrum) Sternum & ribs Appendicular skeleton (limbs) Upper Lower Pectoral girdle Pelvic girdle (Scapula & (2 hip bones clavicle) & sacrum) Free limbs Humerus (arm) Femur (thigh) Radius & ulna (forearm) Tibia & fibula (leg) Carpals, metacarpals Tarsals, metatarsals & phalanges (hand) & phalanges (foot)

6 Classification of Bones: By Shape Long bones: - Longer than they are wide (e.g., humerus, metacarpals) - Consists of a shaft (diaphysis) plus 2 expanded ends (epiphysis)

7 Classification of Bones: By Shape Short bones: - Cube-shaped bones of the wrist and ankle - Sesamoid bones (bones that form within tendons, e.g. patella)

8 Classification of Bones: By Shape Flat bones: - Thin, flattened, and a bit curved (e.g., sternum, most skull bones)

9 Classification of Bones: By Shape Irregular bones: - Bones with complicated shapes (e.g., vertebrae, hip bones)

10 Mature (adult) Bone Trabecular bone Cortical bone Bloom & Fawcett, 12 th ed., p. 195

11 Cortical Bone (Compact bone) Dense, compact Thickest in shaft of long bones Resists bending and shearing

12 Trabecular Bone (Spongy, Cancellous bone) Spongy, trabecular Architecture provides strength (cross-ties, arcades) Resists compression Abundant at ends of long bones, vertebrae, pelvic bones Metabolically more active than cortical bone

13 Trabecular Vs. Cortical Bone Mass Surface area Trabecular 20% 80% Cortical 80% 20% Cancellous = Spongy = Trabecular Cortical = Compact

14 Compact and Cancellous Bone

15 Wall of a Long Bone Lacuna(e) Junqueera & Carneiro, 10 th ed. p. 144

16 Long Bone Anatomic Features Growth plate Epiphysis Metaphysis Diaphysis Endosteum Periosteum

17 In Howship s lacuna (resorption bay) Bone cells

18 Osteoblast Differentiation Cbfa1-deficient mice Wnt and BMP are implicated in skeletal development. BMP induces the expression of Cbfa1 and Wnt promotes osteoblastogenesis. Cbfa1: core-binding factor family gene Kierszenbaum p.125

19 Osteoblast Matrix vesicles Kierszenbaum p. 122

20 Bone Formation and Modeling Osteoid

21 Weiss, 6 th ed., p. 225 EM of Active Osteoblasts osteoid

22 Osteoclasts c Wheater s 5 th ed., p. 190 Howship s lacuna

23 Osteoclast (EM) Note the ruffled border of the cell and resorbing bone matrix Ruffled border Bloom & Fawcett, 12 th ed., p. 210

24 Osteoclast and Bone Resorption Osteopontin

25 Bone Formation Intramembranous Ossification: Forms directly from the embryonic mesenchyme. (Most flat bones of the skull and face) Endochondral Ossification: Initially hyaline cartilage model is formed, which is replaced by bone. (Long bones of the extremities) The basic mechanism of bone deposition is the same in both ossification processes osteoblasts laying down layers of bone appositionally.

26 Cartilage There are three types of cartilage: Hyaline cartilage (Type II collagen): Articular surfaces, Tracheal wall, etc Elastic cartilage (Type II collagen, elastic fibers) Pinna of the ear, Epiglottis, Eustachian tube, etc. Fibrocartilage (Type I & Type II collagen): Intervertebral disks, Pubic symphysis, insertion sites of tendons and ligaments

27 Hyaline cartilage Elastic cartilage Fibrocartilage Type II collagen fibers articular surfaces, epiphyseal plates, trachea, nasal septum, etc. Type II collagen & elastic fibers. Pinna of ear, epiglottis, Eustachian tube, etc. Type I and II collagen fibers. Intervertebral disks, etc (no perichondrium)

28 Beginning of cartilage Formation pluripotent

29 Growth of Hyaline Cartilage Chondrocytes Interstitial growth

30 Hyaline cartilage chondrocytes Synthesize collagen fibers and produce ground substance.

31 Student will describe Development of Bone - the general anatomy of bone and cartilage at the organ and tissue level - the stages/steps of endochondral and intramembranous bone development - the concept of coupling and how bone is remodeled and maintained during homeostatsis

32 Development, a dynamic procedure

33 How is the skeletal system developed? 1. Differentiation of bone related cells Osteoblasts/osteocytes Osteoclasts Chondrocytes 2. Patterning and positioning 3D-polarity Segmentation Specification 3. Size and shape Growth factors Hormones Environment

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36 Developmental Events Formation of the Bony Skeleton - Before week 8, the human embryonic skeleton is made of fibrous membranes and hyaline cartilage - After week 8, bone tissue begins to replace the fibrous membranes and hyaline cartilage

37 Student will describe Development of Bone - the general anatomy of bone and cartilage at the organ and tissue level - the stages/steps of endochondral and intramembranous bone development - the concept of coupling and how bone is remodeled and maintained during homeostatsis

38 9th Week (Months 3-9) = Fetal Period FIBROUS REPLACEMENT BONE (Membranous ossification of neurocranium) Bone spicules Parietal bone Frontal bone Occipital bone Nasal bone Cervical vertebrae Maxilla Mandible

39 Sizes and shapes of each bone in skull / face determine the shape. (Sadler, 2012) (Mishina, 2014) Human Mouse

40 Bones are formed through two distinct processes Intramembranous Ossification Endochondral Ossification

41 Bones are formed through two distinct processes Intramembranous Ossification Endochondral Ossification E12.5 E14.5 E15.5 osteoblast proliferation formation of collagen fibril E18.5 proper patterns of calcification

42 Intramembranous Ossification

43 Intramembranous Bone Formation Bone forms directly from mesenchyme Condensation of mesenchymal cells Proliferation and osteoblastic differentiation Deposition of fibrous matrix Mineralization of matrix Continued growth at sutures, endosteum, periosteum (apposition) time mesenchymal condensation (proliferation) osteoprogenitor (proliferation & differentiation) osteoblast (osteogenesis) osteocyte (osteogenic maturation) apoptosis

44 Bones are formed through two distinct processes Intramembranous Ossification Endochondral Ossification E12.5 E14.5 E15.5 osteoblast proliferation formation of collagen fibril E18.5 proper patterns of calcification

45 Disorders of the skull vault in human Craniosynostosis caused by premature fusion of sutures Parietal foramina Wilkie AO & Morriss-Kay GM, Nature reviews, Genetics, 2001

46 Bones are formed through two distinct processes Intramembranous Ossification Endochondral Ossification

47 Endochondral Bone Formation (Endochondral Ossification) Mouse embryo, E14.5 Mouse embryo, E18.0 First, cartilage primordia are formed (blue). Then, osteoblasts replace cartilage (red).

48 Endochondral Bone Formation (Endochondral Ossification) - Hyaline cartilage model develops from mesenchymal cells - Cartilage cells (chondrocytes) enlarge and their lacunae grow - The surrounding matrix breaks down - Chondrocytes die and degenerate

49 A: Cartilage model Development of a Long Bone from a Cartilage Model (Summary) 1 o center of ossification (B-D) B: Periosteal bone collar forms before cartilage calcification. C: Cartilage begins to calcify. D: Periosteal bud (blood vessels and perivascular. mesenchyme) enters the calcified cartilage. E: Growth plates. 2 o center of ossification F&G: blood vessels and mesenchyme invade epiphyseal cartilage to form 2ocenter and growth plate. Closure of epiphyses H&I: growth plates disappear, epiphyseal and metaphyseal trabeculae fuse.

50 Secondary Ossification Center, Epiphyseal Plate and Metaphysis

51 How Does Development of Growth Plate Influence Size of Long Bones? Resting zone Proliferative zone Prehypertrophic zone Hypertrophic zone

52 How Does Development of Growth Plate Influence Size of Long Bones? 1. Chondrocytes need to proliferate. Resting Proliferative Prehypertrophic Hypertrophic If suppressed, bones become shorter. FGF 2. Chondrocytes need to differentiate. If differentiate too quickly, less time to proliferate. PTHrP, Hedgehog (Bone Growth and Remodeling, then Growth in long bones)

53 Student will describe Development of Bone - the general anatomy of bone and cartilage at the organ and tissue level - the stages/steps of endochondral and intramembranous bone development - the concept of coupling and how bone is remodeled and maintained during homeostatsis

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