Bone PDF

# Bone - Bone is a mineralized connective tissue - 28% type I collagen - 5% noncollagenous matrix proteins - bone sialoprotein - osteocalcin - osteonectin - osteopontin - proteoglycans - Growth factors and serum proteins are found in bone - **Bone...

# Bone - Bone is a mineralized connective tissue - 28% type I collagen - 5% noncollagenous matrix proteins - bone sialoprotein - osteocalcin - osteonectin - osteopontin - proteoglycans - Growth factors and serum proteins are found in bone - **Bone** is composed of: - **67% Inorganic** - Hydroxyapatite - **33% Organic** - 28% Collagen - 5% Noncollagenous proteins - This organic matrix is permeated by: - **Hydroxyapatite** makes up the remaining 67% of bone. - The mineral is in the form of small plates, most of which lodge in the holes and pores of collagen fibrils. - **Bone** composition and structure reflects the activity of the cells involved in the formation of the organic matrix. - Bone from different anatomic sites, developmental stages, exhibits different bulk, biochemical properties, organizations, and collagenous and non-collagenous components. - In addition to **Bone's** obvious functions of: - Support - Protection - Locomotion - **Bone** constitutes an important reservoir of minerals. - **Bone** is controlled by: - Systemically, hormonal factors - Locally, mechanical forces - Including tooth movement - Growth factors - Cytokines - There is evidence that there is central nervous system control of bone mass mediated by a neuroendocrine mechanism. - **Bone** resists compressive forces best and tensile forces least. - **Bone** also resists forces applied along the axis of its fibrous component. - **Bone** fractures most readily due to tensile and slicing stresses. - **Bone** may be classified as: - **Long Bones** - Tibia - Femur - Radius - Ulna - Humerus - **Flat Bones** - All skull bones - Sternum - Scapula - Pelvis - **Bone** characteristics: - Dense outer sheet of compact bone - Central, medullary cavity - Filled with red or yellow bone marrow - Interrupted by a network of bone trabeculae - Trabecular - Cancellous - Spongy bone - **Bone** types have different metabolic responses - Mature or adult bones, whether compact or trabecular, are histologically identical in that they consist of microscopic layers or lamellae. - **Bone** layering: - Circumferential - Concentric - Interstitial - **Bone** is composed of: - **Circumferential Lamellae** - Enclose the entire adult bone - Form its outer and inner perimeters - **Concentric Lamellae** - Make up the bulk of compact bone - Form the basic metabolic unit of bone, the osteon (also called the haversian system) - **Interstitial Lamellae** - Interspersed between adjacent concentric lamellae and fill the spaces between them. - Fragments of preexisting concentric lamellae from osteons created during remodeling that can take a multitude of shapes - **Osteon** is a cylinder of bone generally oriented parallel to the long axis of the bone. - Contains a **Haversian Canal** - Lined by a single layer of bone cells that cover the bone surface. - Houses a capillary. -Adjacent **Havsersian Canals** are interconnected by **Volkmann Canals** - Contain blood vessels - Create a rich vascular network - **Periosteum** - Connective tissue membrane that surrounds the outer aspect of every compact bone - Composed of two layers: - **Fibrous Layer** - Dense, irregular connective tissue - **Inner Layer** - Contains bone cells, their precursors, and a rich microvascular supply. - **Endosteum** - Covers the internal surfaces of compact and cancellous bone. - Not well demarcated - Composed of loose connective tissue containing osteogenic cells. - **Bone Cells** - Different cells are responsible for the formation, resorption, and maintenance of osteoarchitecture. - Two lineages present in bone: - **Osteogenic Cells** - Form and maintain bone - **Osteoclasts** - Resorb bone - **Osteoblasts** - Mononucleated cells that synthesize the organic matrix of bone - Arise from pluripotent stem cells - Mesenchymal origin in the axial and appendicular skeleton - Ectomesenchymal origin (neural crest cells that migrate in mesenchyme) in the head. - Both preosteoblasts and osteoblasts can undergo mitosis during prenatal development and occasionally during postnatal growth. - Exhibit high levels of alkaline phosphatase activity on the outer surface of their plasma membrane. - Cleaves inogranically bound phosphate - Liberated phosphate likely contributes to the initiation and progressive growth of bone mineral crystals. - Plump, cuboidal cells - Slightly flattened cells - Primarily responsible for production of the organic matrix of bone - Exhibit abundant and well-developed protein synthetic organelles. - Secretory products include: - Type I collagen - Type V collagen - Proteoglycans - Noncollagenous proteins - Collagen type 1 molecule is formed and assembled in fibroblasts and odontoblasts in the rough endoplasmic reticulum and Golgi compartments. - Collagen-containing secretory granules release their contents primarily along the surface of the cell apposed to forming bone. - Molecules assemble extracellularly as fibrils and accumulate as a layer of uncalcified matrix called osteoid (prebone). - Noncollagenous proteins also are released mainly along the surface of osteoblasts apposed to osteoid and diffuse from the osteoblast surface toward the mineralization front where they participate in regulating mineral deposition. - **Mineralization Front** - Mineralization foci can be seen within osteoid - Noncollagenous proteins like bone sialoprotein and osteopontin accumulate within them. - The hormones most important in **Bone** metabolism are: - Parathyroid hormone (PTH) - 1,25- ihydroxyvitamin D - Calcitonin - Estrogen - Glucocorticoids - Parathyroid hormone and vitamin D are dual - Enhance bone resorption at high concentrations - Support bone formation at lower concentrations - Calcitonin and estrogen inhibit resorption - Glucocorticoids inhibit resorption and formation, but primarily formation. - Osteoblasts form a cell layer over the forming bone surface and have been proposed to act as a barrier to control ion flux into and out of bone. - When bone is no longer forming, - Osteoblasts flatten substantially - Extend along the bone surface - These cells, termed **bone lining cells**, contain few synthetic organelles. - Implicated in the production of matrix proteins - Bone lining cells cover most surfaces in the adult skeleton. - It has been postulated that bone lining cells retain their gap junctions with **osteocytes** - Create a network that functions to control mineral homeostasis and ensure bone vitality. - **Osteocytes** - Become trapped in matrix they secrete - Mineralized or unmineralized - Number of osteoblasts that become osteocytes varies depending on the rapidity of bone formation, the more rapid the formation, the more osteocytes are present per unit volume. - Embryonic (woven) bone and repair bone have more osteocytes than does lamellar bone - After their formation, osteocytes become reduced in size. - Space in matrix occupied by an osteocyte is called the **osteocytic lacuna.** - **Canaliculi** - narrow extensions of these lacunae - Form enclosed channels - House radiating osteocytic processes of osteocytes. - Osteocytes maintain contact with adjacent osteocytes and with the osteoblasts on the bone surface. - This places osteocytes in an ideal position to transduce signals that affect the response of the other cells involved in bone remodeling and particularly for the repair of microcracks. - Failure of any part of this interconnecting system results in hypermineralization (sclerosis) and death of the bone. - **Osteoclasts** - Multinucleated osteoclasts are much larger than other bone cells - Identified easily under the light microscope - Often seen in clusters - Characterized by possessing tartrate-resistant acid phosphatase. - Present within the cytoplasmic vesicles and vacuoles - Distinguishes it from multinucleated giant cells - Typically osteoclasts are found against the bone surface, occupying hollowed-out depressions, called **Howship's lacunae,** that they have created. - Microscopy of bone-resorbing surfaces shows that **Howship's lacunae** are often shallow troughs with an irregular shape reflecting the activity and the mobility of **osteoclasts** during active resorption. - Multinucleated osteoclasts exhibit a unique set of morphologic characteristics - **Ruffled Border** - Deep folds formed by the cell membrane adjacent to the tissue surface. - **Sealing Zone** - Peripheral to ruffled border - plasma membrane is apposed to the bone surface - Contains Actin, Vinculin, and Talin. - Attaches the cell to the mineralized surface. - Isolates a microenvironment between the osteoclast and the bone surface. - Often an **interfacial matrix layer (lamina limitans)** is observed between the sealing zone and the calcified tissue surface - Multiple nuclei - Numerous Golgi complexes, mitochondria, rough endoplasmic reticulum, and vesicular structures situated between the Golgi complex and resorption surface - Rich in acid phosphatase and other lysosomal enzymes. - Enzymes are synthesized in the rough endoplasmic reticulum - Transported to the Golgi-complexes - Moved to the ruffled border in transport vesicles - Release their content into the sealed compartment adjacent to the bone surface - Proton pump associated with the ruffled border that pumps hydrogen ions into the sealed compartment. - Resorptive events: - Attachment of osteoclasts to the mineralized surface of bone - Creation of a sealed acidic microenvironment through action of the proton pump - Demineralizes bone - Exposes organic matrix. - Degradation of the exposed matrix by the action of released enzymes like acid phosphatase and cathepsin B. - Endocytosis of organic degradation products at the ruffled border - Translocation of degradation products in transport vesicles and extracellular release along the membrane opposite the ruffled border (transcytosis) - Several mechanisms bind the osteoclasts to surfaces - Concentration of arginine-glycine-aspartic acid containing molecules - Bone sialoprotein, osteopontin on bone surfaces (lamina limitans) - Facilitate osteoclast adhesion and formation of the sealing zone.