BONE

Specialized form of connective tissue composed of cells and extracellular matrix. Provide support and protection Serve as storage site for calcium and phosphate Mineralized by calcium phosphate in the form of hydroxyapatite crystals Structural components of bone matrix: a. Type I collagen 90% b. Type V collagen c. Ground subs 10% - noncollagenous proteins - bone devt, growth, remodeling, repair c.1. Proteoglycan Macromolecules - core protein with side chains of glycosaminoglycans hyaluronan chondroitin sulfate keratan sulfate - compressive strength of bone - bind growth factors - may inhibit mineralization c.2. Multiadhesive Glycoproteins - attachment of bone cells and collagen fibers osteonectin - glue collagen and hydroxyapatite crystals sialoproteins osteopontin - cells to bone matrix sialoprotein I and II - mediate cell attachment - initiate calcium phosphate formation

c.3. Bone-specific, vitamin K-dependent proteins osteocalcin - capture Ca from circulation - attract & stimulate ostoeclasts protein S - removal of apoptotic cells matrix gla-protein (MGP) - devt of vascular calcifications c.4. Growth factors & cytokines - regulatory proteins: IGFs, TNF-, TGF-, PDGF, BMPs, IL-1, IL-6 BMPs are the most unique; induce differentiation of mesenchymal cells into osteoblasts * Bones are the organs of the skeletal system * Bone tissue - structural component of bones Bone tissue classification COMPACT SPONGY Substantia compacta Substantia spongiosa Dense layer Spicules, trabeculae Ouside of bone Interior of bone Seen with aid of Interconnecting cavities microscope Bone classification: shape: a. long bones - longer in one dimension ex. Tibia, metacarpals b. short bones - equal in length and diameter ex. Carpals of hand c. flat bones - thin and platelike ex. Calvaria, sternum d. irregular bones ex. Vertebra, etmoid bone (spaces)

Long Bone - page 220, figure 8.2 diaphysis shaft epiphysis expanded ends metaphysis flared portion marrow medullary cavity periosteum fibrous CT capsule * Shaft: compact > spongy * Ends: spongy > compact Outer Surface of Bones Periosteum - dense fibrous CT - outer covering of bone * actively growing bone - outer layer: dense CT - inner layer: osteoprogenitor cells * bone not in progress - in&out fibrous layer (dense CT) Periosteal cells - may undergo division (become osteoblasts) under appropriate stimulus Sharpeys fibers - collagen fibers of the ECM of bone tissue - perforating fibers - outer fibrous layer of periosteum Bone Cavities Endosteum - lining tissue - one cell layer thick - osteoprogenitor cells = endosteal cells - can differentiate into osteoblasts and bone-lining cells * in compact bone facing marrow cavity * in spongy bone trabeculae w/in cavity Red bone marrow - blood cells in different stages of devt * become yellow marrow in adults - found in: sternum, iliac crest

Mature Bone - lamellar bone - page 222, figure 8.3 Lacunae - spaces which contain the osteocyte Haversian systems - osteons - cylindrical units - concentric lamellae surrounding a central canal Osteonal (Haversian) canal - contain vascular and nerve supply Perforating (Volkmanns) canals - connect osteonal canals to one another - not surrounded by concentric lamellae Canaliculi - passage bet. osteocytes & blood vessels Interstitial lamellae - remnants of concentric lamellae Circumferential lamellae - entire inner and outer circumferences of the shaft of a long bone Cement lines - demarcates the limit between the Haversian and Interstitial system IMMATURE BONES Non-lamellar, bundle, woven Random cell arrangement (+) Ground substance Hematoxylin Not mineralized heavily Rapid formation Found in fetus In alveolar sockets of oral cavity, tendon-bone insertion In adults MATURE BONES Lamellar Same as lamellae Eosin Prolonged secondary mineralization

CELLS OF BONE TISSUE

OSTEOPROGENITOR CELLS Flattened or squamous cells OSTEOBLASTS Cuboidal or polygonal cells, single layer, apposition to forming bone Mature matrix: Acidophilic Bone-forming cells OSTEOCYTES Smaller cells, reduced perinuclear cytoplasm, in lacuna Slightly basophilic Maintain bone matrix. BONE-LINING CELLS Flat cells, attenuated cytoplasm OSTEOCLASTS Large, multinucleated

Slightly basophilic Osteoblast precursor cells

Slightly basophilic Maintenance & nutritional support of osteocytes From osteoblast

Acidophilic Bone resorption

From mesenchymal stem cells, Inner periosteum

Differentiated osteoprogenitor cell

Osteoblast surrounded by osteoid

From GMP (Granulocyte/ macrophage progenitor cells)

Osteoprogenitor Cells periosteal cells endosteal cells - line marrow cavities of Haversian canal Osteoblasts - flat or attenuated when inactive - secretes bone matrix Type I collagen 90% Osteoid BMPs - initial unmineralized bone * when surrounded by osteoid matrix, becomes an osteocyte Osteocytes Mechanotransduction - respond to mechanical forces death of osteocytes results in resorption by osteoclasts, followed by repair by osteoblasts. - communicate by: gap junctions signaling molecules - nitric oxide - glutamate transporters

Bone-Lining Cells periosteal cells - external bone surface enosteal cells - internal bone surface - regulate movement of Ca and PO4 into & out of the bone Osteoclasts Resorption bay - Howships lacuna - shallow bay under osteoclast * Needs to be activated to become bone-resorbing cell Three specialized regions of osteoclast of actively resorbing bone: a. ruffled border - direct contact with bone - finger-like projections - surface area for exocytosis b. clear zone - ringlike perimeter, actin filaments - demarcates the bone area being resorbed ECM adhesion molecules - tight seal between plasma c. basolateral region - exocytosis of digested material TRAP

BONE FORMATION Endochondral ossification Itramembranous ossification Endochondral ossification - cartilage model as bone precursor - bones of extremities, vertebrae * 2nd trimester of fetal life to early adulthood different zones in the epiphyseal cartilage zone of reserve cartilage - resting zone, no proliferation zone of proliferation - hyaline cartilage, chondrocyte columns - abundant matix between chondrocytes zone of hypertrophy - enlarged cartilage cells - metabolically active chondrocytes zone of calcified cartilage - hypertrophied cells begin to degenerate\ - calcification zone of resorption/ossification - nearest the diaphysis - in direct contact with CT of marrow cavity * secondary ossification center - cartilage undergoes hypertrophy and degenerates - only epiphyseal growth plate remains Epiphyseal growth plate * The thickness remains constant during growth * amount of new cartilage = amount of resorbed * resorbed cartilage is replaced by spongy bone * actual lengthening of the bone occurs when new cartilage matrix is produced at the epiphyseal plate * new cartilage pushes the epiphysis away from the diaphysis, elongating the bone * bone increases in width when aposistional growth of new bone occurs between the cortical lamellae and the periosteum

SCHEMATIC DIAGRAM OF DEVELOPING BONE

1. periosteal collar of bone forms around the diaphysis 2. bony collar calcifies 3. blood vessels and connective tissue cells invade the cartilage 4. primary center of ossification develops 5. periosteal bone is formed and perivascular cells invade the proximal epiphyseal cartilage 6. secondary ossification center is established in the proximal epiphysis 7. secondary (epiphyseal) ossification center forms at the distal end 8. epiphyseal cartilage is formed between each epiphysis and diaphysis. distal epiphyseal cartilage diasppears with continued growth 9. proximal epiphyseal cartilage disappears with growth cessation 10. metaphysis becomes continuous with epiphysis, epiphyseal lines remain Intramembranous ossification - simpler, no cartilage precursor - flat bones, clavicle - of mesenchymal cells into osteoblasts * 8th week of gestation in humans 1. mesenchymal cells (MC) migrate and aggregate in areas where bone is destined to form 2. MC differentiate into osteoprogenitor cells expressing Cbfa1 transcription for osteoblast diffrentiation 3. differentiated osteoblasts 4. osteoblasts secrete componets of bone matrix 5. woven obone or intramembranous bone is formed