1. CARTILAGE AND BONE Similarities Living cells embedded in a matrix produced by themselves Cells occupy spaces in the matrix called lacunae Both develop from mesenchyme Both are covered by connective tissue Differences Nutrition of cells Growth

2. isogenous group perichondrium matrix Histological preparation of hyalin cartilage lacunae cell territorial matrix Chondrocytes - interstitial growth Chondroblasts- appositional growth Several growth factors : FGF, IGF, TGF-  and growth hormone influence cartilage growth

3. Condrocytes inside hyaline cartilage matrix territorial matrix Isogenous group

4. EM of chondrocyte and surrounding matrix territorial matrix proteoglycans collagen type II fibrils

5. piokl Proteoglycan aggregate

6. Cartilage matrix content Water ≈ 70% Organic components ≈ 30% (Collagen type II ≈ 40% and Proteoglycans ≈ 60%) As a result the matrix has a gel-like strucure that allows nutrition by diffusion and provides flexibility and mechanical resiliance It also makes possible formation of isogenous groups by division of chondrocytes into the matrix and for interstitial growth of cartilage from inside

7. Types of cartilage All of them contain collagen type II plus: Hyalin cartilage---- Elastic cartilageelastic fibers Articular cartilage collagen type I Fibrocartilagecollagen type I

8. Elastic cartilage elastic fiber perichondrium

9. Articular cartilage synovial cavity articular cartilage bone bone marrow no perichondrium !

10. Fibrocartilage rows of chondrocytes collagen type I fibres dense connective tissue Found around nucleus pulposus of intervertebral disks. Again, no perichondrium !

11. Poor regeneration of cartilage Except in young chidren, damaged cartilage regenerates with difficulties by activation of perichondrium. If damage is extensive, perichondrium produces a scar of dense connective tissue

12. Bone BONE

13. Bone

14. compact/corticalcancelous/trabecular/spongy trabeculae/spicules Longitudinal section of adult long bone Bone classification

15. Blood vessels in a system of Haversian canals interconnected with Volkman’s canals 0steon - complex of concentric lamellae of bone surrounding a Haversian canal Interstitial lamellae Cementing substance Inner circumferential lamellae Outer circumferential lamellae endosteum periosteum

16. Lacunae of osteocytes Cement line Interstitial lamellae Osteon with Haversian canal Thin section of calcified bone

17. Histological preparation of decalcified bone Osteons with Haversian canals Bone marrow Volkman’s canal Inner circumferential lamellae

18. Primary, immature or woven bone (decalcified preparation) Beginning of formation of osteons, but well defined lamellae are not yet formed Spicule/trabecular (~0.2 mm)

19. CELLS OF BONE Mesenchymal cells differentiating into osteoblasts Capillary Not calcified bone matrix osteoid Osteocytes in lacunae with their processes interconnected Calcified bone matrix is penetrated by canaliculi

20. Calcification/mineralization of of bone matrix Inorganic matter is ≈ 50% of the dry weight of bone matrix mainly in form of hydroxyapatite crystals - Ca10(PO4)6(OH)2 Initial mineralization in woven bone or cartilage by matrix vesicles deposited by osteobalsts and chondrocytes and enriched in alkaline phosphatase and acidic phospholipids Mineralization front - mineralization of matrix synthesized at already calcified mature bone surface Deficiency of Ca and vitamin D negatively influence normal calcification process

21. blood vessel osteocytes canaliculi flat/resting osteoblasts osteoclast calcified bone matrix

22. ruffled border clear/adhesion zone

23. Howship’s lacunae osteoblasts making new bone

24. Remodeling activation of osteoclasts Parathyroid hormone inhibition of osteoclasts Calcitonin activation of osteoblasts osteoid Calcification of new bone and surface recovery Bone turnover and skeletal homeostasis In a young adult ≈ 30% of the total skeletal mass is renewed every year by remodeling in a balanced fashion Shfting the balance between bone formation and bone resorbtion - osteoporosis, osteopetrosis

25. FORMATION OF HAVERSIAN CANAL Activation of osteoclasts Inhibition of osteoclasts Activation of osteoblasts First concentric layer Second concentric layer

26. Intramembranous bone formation Activation of mesenchymal cells to turn into osteoblasts Osteoblasts start to produce noncalcified bone matrix (osteoid) New bone spicule/trabecular starts to grow Process of remodeling starts Calcified matrix osteoid

27. Intramembranous formation of bones of the skull New bone spicules/trabeculae growing Active osteoblasts producing osteoid Calcified matrix

28. Intramembranous bone formation active osteoblasts producing osteoid osteoid osteocytes locked in bone matrix resting osteoblasts

29. 1. Starting with cartilage model 2. Formation of bony collar at the middle of diaphysis 3. Hypertrophy of chondrocytes followed by calcification of their marix and their death 4. Invasion of osteoclasts followed by blood vessels and osteogenic cells 5. Beginning of new bone synthesis over the calcified cartilage matrix 6. Formation of primary center of ossification 7. Remodeling and growth 8. Later a secondary center of ossification appears in the epiphyses that is separated from the primary center by growth plate of cartilage Endochondral bone formation

30. Starting with cartilage model Hypertrophy and degeneration of chondrocytes

31. Bony collar on the surface at the middle of diaphysis formed by intramembranous bone formation Beginning of formation of primary center of ossification

32. Propagation of the process of primary ossification followed by remodeling of the newly formed bone trabeculae Closer look at this area next At the same time formation of bony collar also continues by Intramembranous bone formation

33. Columns of dividing chondrocytes - interstitial growth Hypertrophy of chondrocytes Calcification of cartilage matrix and death of chondrocytes Invasion of blood vessels and osteogenic cells and beginning of bone formation over calcified cartilage matrix Remodeling starts

34. Formation of secondary center of ossification

35. Secondary center of ossification Growth/epiphysial plate Advancing of primary ossification Epiphysis Diaphysis Metaphysis

37. Endochondral bone formation 1. Starting with cartilage model 3. Hypertrophy and degeneration of chondrocytes and calcification of their marix 2. Formation of bony collar on the surface at the middle of diaphysis 4. Invasion of osteoclasts followed by blood vessels and osteogenic cells 5. Beginning of new bone synthesis over the calcified cartilage matrix 6. Formation of primary center of ossification 7. Remodeling and growth 8. Later a secondary center of ossification appears in the epiphysis