LECTURE 12_ DEVELOPMENT OF CARTILAGE AND BONE_DISORDERS OF GROWTH.pptx

Surgical Anatomy of Cartilage
development, microscopic
anatomy, disorders of surgical relevance

1. Development of cartilage and bone/disorders of growth

2. Cartilage intro Type of dense connective tissue Organizational Structure- Cells embedded in a firm matrix containing fibers and ground substance. Ground substance comprises of proteoglycan molecules, water and dissolved salts. Three types: Hyaline Cartilage Fibrocartilage Elastic cartilage

3. Development Develops from mesenchyme-5 th week Mesenchyme condenses to form chondrification centers. Differentiation of mesenchymal cells- precondrocytes - chondroblasts Chondroblasts secrete extracellular matrix(collagenous fibrils and ground substance). Subsequently collagenous fibers or elastic fibers or both are deposited in the intercellular substance. Matrix can be used to differentiate the three types of cartilage.

4. Growth Regulation Growth is attributable to two processes Appositional –’growth from outside’: chondroblasts in perichondrium secrete matrix Interstitial-chondrocytes within undergo mitotic divisions and secrete new matrix e.g epiphyseal plates and articular cartilage GH, TH, Testosterone accelerates synthesis of glycosaminoglycans while cortisone and estradiol inhibits synthesis.

5. Bone development Two main processes Intramembranous ossification Endochondral ossification. In general bones of the vault of the skull, face and clavicle ossify in membrane, while long bones ossify in cartilage

6. Intramembranous Ossification Direct conversion of mesenchyme into bone without prior cartilage Mesenchyme condenses and its cells differentiate into osteoblasts and group into ossification center. Osteoblasts secrete osteoid ( unmineralized ) . Calcium phosphate is deposited in osteoid Osteoblasts become entrapped by the osteoid they secrete and transform to osteocytes. Trabecular bone and periosteum form Cortical bone forms superficially to the trabecular bone. Blood vessels form the red bone marrow

7. Conti..

8. Endochondral ossification Formation of bone from pre-existing cartilaginous model. Mesenchymal cells differentiate into chondrocytes and form cartilage model of bone. Chondrocytes near the center of the model undergo hypertrophy and alter the contents of matrix they secrete enabling mineralization. Chondrocytes undergo apoptosis due to decreased nutrient availability; blood vessels invade bringing osteogenic cells Primary ossification center forms in the diaphyseal region of the periosteum called the periosteal collar Secondary ossification centers develop in the epiphyseal region after birth.

9. Bone growth-Interstitial growth

10. Appositional growth

11. Conti..

12. Molecular Regulation of bone growth Several transcription factors involved in endochondral ossification. Sox-9 regulates chondrogenesis of collagen type II, IV and XI PTHrp delays chondrocyte differentiation in the zone of hypertrophy. Intramembranous ossification is controlled by the canonical Wnt and Hedgehog signaling pathway. Beta Catenin enters cells to induce formation of osteoblasts Additional transcription factors involved include CBFA1(Runx2), osterix (OSX) and Sclerostin (SOST)

13. Other factors influencing growth. Minerals : Large amounts of calcium and phosphorous and smaller amounts of magnesium, manganese and fluoride needed when bones are growing. Vitamins : Vitamin A stimulates activity of osteoblasts Vitamin C needed for synthesis of collagen Vitamin D-absorption of calcium Vitamin K and B12-needed for bone protein synthesis Hormones : Insulin like growth factor-stimulates osteoblasts, promote cell division at epiphyseal plate and periosteum Thyroid hormone-stimulates osteoblasts Insulin-promotes synthesis of bone proteins. Sex hormones- growth spurt in puberty, closure of epiphyses bone remodeling Nutrition and weight bearing exercises .

14. Defective collagen Osteogenesis Imperfecta Also known as Brittle bone disease Results from defective type 1 collagen production leading to congenital osteopenia with increased bone fragility, low bone mass and other connective tissue manifestations . Associated with mutations in COL1A1(collagen type 1 alpha 1 chain) and COL1A2) Classical clinical triad of fragility of bone, blue sclera and deafness Sillence classification into 4 types based on severity, mode of inheritance and blue sclera. Genetic counselling, Physiotherapy, rehabilitation and orthopedic surgery, more recently bisphosphonates. b. Enhler danlos syndrome Results from mutations in several genes that control assembly of collagen and its interaction with other ECM proteins. This leads to lowered structural integrity of cartilage and bone.

15. Inadequate calcification Osteomalacia and Rickets Pathophysiologic characteristic-failure of bone to mineralize both in the osteoid of long bones and at the growth plate. Clinical characteristic-skeletal deformities Causes- Calcipenic or phosphopenic .