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Specialized type of connective tissue with a calcified extracellular matrix in which characteristic cells are embedded. Bone Functions - Support & protection - Harbors hematopoietic tissue (bone marrow) - Movement - Calcium reservoir |
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I.CELLS II.ECM – Bone Matrix– calcified |
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A.INORGANIC COMPONENT 65% of its dry weight - crystals of calcium hydroxyapatite (calcium and phosphate) - (with other components, bicarbonate, citrate, magnesium, Na and K.) B. ORGANIC COMPONENT 35% of its dry weight Predominantly TYPE I COLLAGEN -tensile strength. Ground substance: - GAG’s - chondroitin sulfate & keratan sulfate. - Glycoprotein: osteonectin & osteocalcin – bone mineralization; & osteopontin (OPN) – a sialoprotein - mediates hydroxyapatite binding and cell attachment (sealing zone) |
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1. PERIOSTEUM 2. ENDOSTEUM |
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- a layer of noncalcified CT covering bone on its external surfaces, except at synovial articulations and muscle attachments. - It is composed of an outer, fibrous, dense collagenous layer and an inner cellular osteoprogenitor (osteogenic) layer. - Sharpey’s fibers- bundles of collagen fibers in the periosteum that penetrate into the bone matrix, binding periosteum to bone. - Functions to distribute blood vessels to bone. |
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- a specialized thin, reticular CT composed of a monolayer of osteoprogenitor cells and osteoblasts lining the internal cavity - Lines the marrow cavity and extends into the haversian canals Principal functions of P &E - Nutrition of osseous tissue & provision of a continuous supply of new osteoblasts for repair or growth of bone. CELLS OF THE |
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1.OSTEOPROGENITOR CELLS 2.OSTEOBLASTS 3.OSTEOCYTES 4.OSTEOCLASTS |
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•Derived from embryonic mesenchymal cells and retain their ability to undergo mitosis and form osteoblasts •Stem cells found in the endosteum and periosteum •Spindle-shaped with pale-staining oval nucleus; sparse RER poorly developed Golgi apparatus with abundant free ribosomes. |
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- Derived from osteoprogenitor cells and possess receptors for parathyroid hormone (PTH). - Synthesis of the org comp of bone matrix - Osteoid = newly made uncalcified matrix - When active they are cuboidal to columnar in shape with basophilic cytoplasm, a well-developed RER and Golgi complex. - Found along the margin of bone. - These cells become entrapped in lacunae but maintain contact with other cells via their cytoplasmic processes. |
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•Mature bone cells derived from osteoblasts that became trapped in their lacunae •Flat nucleus, almond shaped, cytoplasm; poor in organelles •Are in contact with neighboring osteocytes via cytoplasmic processes that extend through small tunnels called canaliculi often through gap junctions. - This arrangement provides limited cytoplasmic continuity between the cells and explains how osteocytes obtain nutrients and oxygen and disposes of wastes at relatively great distances from the BV •Actively involved in the maintenance of the bony matrix (they do not secrete the matrix) •Death of osteocytes result in bone breakdown or resorption |
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- Large, multinucleated, and motile cells - Acidophilic cytoplasm, many lysosomes, many mitochondria - Form by fusion of blood monocyte derivative - MONONUCLEAR PHAGOCYTE SYSTEM - They form and are located in depressions known as Howship lacunae, which represent areas of bone resorption. |
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4 morphologically recognizable regions 1. Ruffled border - site of active bone resorption. It is composed of irregular finger-like cytoplasmic projections extending into the Howship lacunae. Increases the surface area – facilitating in the resorptive process. 2. Clear zone –region immediately surrounding the periphery of the ruffled border. It contains microfilaments, which help osteoclasts maintain contact with the bony surface, and serves to isolate the region of osteolytic activity. 3. Vesicular zone – consist of numerous endocytic and exocytic vesicles that ferry lysosomal enzymes. Between basal and ruffled borders. 4. Basal zone – located on the side of the cell opposite the ruffled border. It contains most of the cell organelles. |
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How does osteoblast regulate osteoclast formation? |
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by secreting three signals. •Osteoclast precursors (macrophages) are stimulated by M-CSF to undergo mitosis. • RANKL (Receptor activator of nuclear factor kappa-B ligand) (OPGL) - binds to the precursor, inducing it to differentiate into the multinucleated osteoclast, thus activating it to commence bone resorption. •Osteoprotegerin (OPG), a member of the tumor necrosis factor receptor (TNFR) family produced by osteoblasts and other cells, can prohibit RANKL from binding to the macrophage, thus prohibiting osteoclast formation. - also known as osteoclastogenesis inhibitory factor (OCIF) |
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•Have parathyroid hormone and vitamin D receptors •Release matrix vesicles •Secrete alkaline phosphatase •Serum alkaline phosphatase is a marker for osteogenesis |
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•Have calcitonin receptors •Secrete collagenase to digest type I collagen of the bone matrix •Urine hydroxyproline level can be monitored to assess bone resorption. |
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3 Steps of Bone Restoration |
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(1) Osteoclasts secrete acid, which decalcifies the surface layer of bone. (2) Acid hydrolases, collagenases, and other proteolytic enzymes secreted by osteoclasts then degrade the organic portion of the bone. (3) Osteoclasts resorb the organic and inorganic residues of the bone matrix and release them into connective tissue capillaries. |
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HORMONAL CONTROL OF BONE RESORPTION |
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- Osteoclast activity is controlled by cytokines and hormones. - Osteoclasts participate in the long – term maintenance of blood calcium homeostasis by their response to parathyroid hormone (PTH) and calcitonin. - PTH stimulates osteoclastic resorption (ruffled borders their activity) Ca2+ (Mediated by a signal from the osteoblasts) - Calcitonin inhibits osteoclastic activity (surface ruffling) blood Ca2+ |
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2 Types of Bone based on gross observation |
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1. Compact Bone 2. Spongy Bone |
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- Forms a thick diaphyseal cylinder of long bones, a thin covering over the epiphyses, and the tables of the flat bones of the skull - Lacks the large spaces and trabeculae - Deposited in a layer over the spongy bone tissue - Provides protection and considerable support. - Located where stresses are limited in direction - Concentric ring microscopic structure - Basic unit of compact bone is an osteon
Diaphysis - shaft; cylindrical with walls of compact bone & a central marrow cavity lined with endosteum |
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SPONGY (CANCELLOUS) BONE –Found at the ends of long bones, called epiphysis, which is separated from the diaphysis by the epiphyseal plate, and between the thick plates, or tables, of the flat bones of the skull, where it is called the diploe. - Consists of bony spicules or trabeculae that enclose bone marrow - located where stresses are weaker or multi-directional - Does not contain Haversian system but there are irregular arrangement of lamella. These contain lacunae housing osteocytes that are nourished by diffusion from the marrow cavity, which is filled with bone marrow - Epiphysis - bulbous articular ends; contains spongy bones |
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Organization of lamellae in compact bone |
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1. Haversian systems (OSTEONS) - Each system is composed of cylinders of lamellae, concentrically arranged around a haversian canal, which contains BV, nerves, and LCT - Surrounded by an amorphous cementing substance. - Volkmann’s canal is a channel that connects adjacent haversian canals; also contain BV from the bone marrow and periosteum. 2. Interstitial lamellae are irregularly shaped lamellae located between haversian systems. They are remnants of remodeled haversian systems. 3. Outer circumferential - outermost region; contains Sharpey’s fibers 4. Inner circumferential - encircles the marrow cavity |
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Red marrow where active hemopoiesis is taking place; contains stem cells Yellow marrow: inactive/reserve tissue; contains many unilocular adipocytes |
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1. DECALCIFIED SECTIONS 2. GROUND SECTIONS |
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- Inorganic component of bone is removed by immersion of the tissue in a decalcifying solution, such as formic acid or nitric acid. The resultant bone may then be sectioned with a microtome. Disadv - The decalcification process preserves cells and some fibers, but obscures other components •Ethylene diamine tetra acetic acid (EDTA) – chelating agent w/c binds to calcium; less damaging to the tissue than acids |
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•Prepared by sawing the bone into thin slices followed by grinding the sections with abrasives between glass plates •Disadv – cells are destroyed and the lacunae & canaliculi are filled in with bone debris |
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Bone Types based on microscopic observation |
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1. Primary Bone 2. Secondary Bone |
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- Immature/Woven bone - First bone to form during fetal development and during bone repair. - It has abundant osteocytes and randomly arranged Type I collagen fibers in the osteoid, which are later replaced & organized as secondary bone, except in certain areas (tooth sockets, near suture lines in skull bones & at insertion sites of tendons) - Low mineral content |
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- Mature/Lamellar bone - All bone in a healthy adult - Osteocytes in their lacunae are dispersed at regular intervals between, or occasionally within the parallel or concentric bony lamella - Composed of regular parallel bands of collagen arranged in sheets. - Matrix is more calcified - Physically stronger and more resilient |
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Histogenesis/Osteogenesis |
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1. INTRAMEMBRANOUS OSSIFICATION 2. ENDOCHONDRIAL OSSIFICATION |
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1. INTRAMEMBRANOUS OSSIFICATION |
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-Occurs within a mesenchymal tissue (direct replacement) - Process by which most of the flat bones (e.g, parietal bones of the skull) are formed 1. Increased vascularity of tissue. 2. Active proliferation of mesenchymal cells. The mesenchymal cells give rise to osteogenic cells, which develop into osteoblasts. This forms an ossification center. 3. Osteoblasts begin to lay down osteoid. Osteoid is the organic part of bone without the inorganic constituent. 4. Osteoblasts either retreat or become entrapped as osteocytes in the osteoid. 5. The osteoid calcifies to form spicules that fuse into a spongy lattice of primary bone. 6. Mesenchyme between the spicules participates in bone marrow development 7. Bone remodeling occurs. Periosteum and compact bone are formed. |
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2. ENDOCHONDRIAL OSSIFICATION |
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Involves replacing cartilage with bone and occurs in all except membrane bones.
Steps: 1. Cartilage model – core cells differentiate into chondroblasts, which divide, secrete cartilage matrix and become chondrocytes. Peripheral cells differentiate into fibroblasts, which form the perichondrium 2. Periosteal bone collar – capillaries penetrate the perichondrium, and mesenchymal stem cells on its inner surface become progenitor cells – undergoes intramembranous ossification. 3. Proliferation, hypertrophy & calcification 4. Primary marrow cavity formed (chondroclasts remove calcified cartilage matrix and dead chondrocytes 5. Periosteal bud – cluster of BV from the periosteum penetrates the primary marrow cavity. 6. Ossification – primary bone and residual calcified cartilage are resorbed and replaced by secondary bone. •Cartilage calcifies during early stages of bone formation; calcified cartilage is basophilic (blue) and new bone is acidophilic (pink). Previous steps may occur more than once during formation of bone. |
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1. Primary center of ossification is formed at the diaphysis, which is the site of increased bone diameter 2. Secondary ossification centers form at each epiphyses 3. Metaphysis – region between primary and secondary ossification center. 4. Ossification centers enlarge until all that separates them is a thin plate with hyaline cartilage at its center - the epiphyseal plate, which is the site of longitudinal growth |
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Zones of the epiphyseal plates |
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- starting from the epiphyseal side of the cart. a. Zone of reserve cartilage (Resting zone) – small inactive (hyaline cartilage) chondrocytes (no morphologic changes) b. Zone of proliferation - rapid mitotic divisions, giving rise to rows of isogenous cell groups. c. Zone of cell hypertrophy and maturation - chondrocytes in stacks enlarged with glycogen accumulation d. Zone of calcification - hypertrophied chondrocytes die; deposition of hydroxyapatite (more basophilic matrix). e. Zone of ossification - borders on the primary marrow cavity. (acidophilic osteoid) formation of calcified cartilage/calcified bone complex |
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MEDICAL APPLICATION(Role of vitamins in bone formation) |
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1. Vitamin D 2. Calcium deficiency 3. Vitamin A 4. Vitamin C |
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- aids in intestinal absorption of dietary calcium & reduces renal calcium excretion - Deficiency – reduces blood calcium |
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– leads to incomplete bone-matrix calcification and, if prolonged, to bone resorption. -Rickets - Juvenile osteomalacia; Bone deformities, including bowed legs -Osteomalacia in adults. - Insufficient calcification of newly deposited bone. - Weakening but not deforming bone (susceptible to fracture and are slower to repair than healthy bones) - Reduced osteoblast activity while osteoclast activity is normal or even elevated. - May be severe during pregnancy because the calcium requirements of the fetus may lead to calcium loss from the mother. |
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- Slows bone growth and affects bone cell distribution. Poor coordination between skull and brain growth rates may cause abnormally high pressure on the brain, thereby damaging the CNS. |
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-slows cartilage growth and accelerates ossification - Excess before birth, especially during cartilage model formation, causes skeletal deformities and deletions. - Excess in childhood/adolescence causes premature epiphyseal closure & small stature. |
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-is necessary for collagen formation. - Deficiency inhibits bone growth and slows fracture repair because ascorbic acid is required for normal collagen synthesis; Scurvy. |
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hormones in bone formation |
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1.Parathyroid hormone (PTH) 2.Calcitonin 3.Growth Hormone |
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(PTH) activates osteoblasts to secrete osteoclast-stimulating factor, which then activates osteoclasts to resorb bone, thus elevating blood calcium levels. •Excess PTH (Hyperparathyroidism) renders bone more susceptible to fracture and subsequent deposition of calcium in arterial walls and certain organs such as the kidney. |
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is produced by parafollicular cells of the thyroid gland. •It eliminates the ruffled border of osteoclasts and inhibits bone-matrix resorption, thus preventing the release of calcium. |
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is produced in the pars distalis of the pituitary gland and stimulates overall growth, especially that of epiphyseal plates. •Too much : Gigantism •Too little : Dwarfism •Adults : Acromegaly - characterized by very thick bones in the extremities and in portions of the facial skeleton |
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Decreasing bone mass – diminished estrogen secretion, osteoclastic resorption is greater than bone deposition, reducing bone mass to a point at which the bone cannot withstand stresses and breaks easily. |
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Genetic disorder characterized by increased density of bone (“marble bones”) - Results from defective resorption of bone by dysfunctional osteoclasts (lack ruffled borders) |
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Excessive bone formation and breakdown, resulting in an increase in cancellous bone compared with compact bone - Osteoblastic activity increases, osteoclasts activity decreases - Usually affect femur, pelvis, spine and skull |
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•Uncommon, bone cells may escape the normal controls of proliferation to become benign (osteoblastoma, osteoclastoma) or malignant (osteosarcoma) tumors |
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–pleomorphic and mitotically active osteoblasts associated with osteoid; adolescents and young adults; lower ends of femur, upper tibia & upper humerus |
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