Bone

Osteoblasts

**Osteoblast build bone -synthesize the organic matrix of bone (*collagen type 1,proteoglycans, GAG's and glycoproteins) -are cuboidal or columnar in shape, cytoplasm stains basophilic because of lots of RER. Form gap junctions with osteoblasts and mainly with osteocyte cells that are trapped in the bone. -cells contain lots of secretory vesicles exocytose them to form osteoid (uncalcified bone matrix) **The cells also have matrix vesicles which is NOT the same thing as secretory vesicles -cells secrete matrix vesicles which arise from plasma membrane into the osteoid. Matrix vesicles have lots of Ca and PO4 ions, ATPase, alkaline phosphate, pyrophosphatase and numerous Ca pumps. -Ca pumps transport Ca into matrix vesicles NOT into secretory vesicles. -alk. Phosphate and pyrophosphate cleave PO4 ions from extracellular matrix - as conc of Ca and PO4 increases, crystallization of CaPO4 occurs and growing hydroxypatite crystals burst the membrane of the matrix vesicles. -hydroxyapatite crystals surround osteoblasts and act as sites of initiation. They grow rapidly and are deposited into gap regions of collagen thus mineralizing the matrix material forming mineralized bone. -Understand the importance of matrix vesicles

Function

-mechanical support for internal organs -permits locomotion via tendons -protects vital organs -Metabolic reservoir of mineral salts (99 percent of Ca)

Composition

- Composed of cells and matrix: Cells -support cells=osteoblast and osteocytes -resorption and remodeling cells osteoclasts Matrix -matrix has inorganic mineral salts and organic materials -non mineralized organic matrix is called osteoid

Inorganic component

-Composed mainly of calcium and phosphorus. Minor elements are Mg, Na, K, HCO3. -Ca and phosphorus form hydroxyapatite crystals as plates alongside collagen type 1 fibrils. They are deposited into gap regions. CaPO4 is also present in an amorphous form. -Surface crystals form a hydration shell with H2O this allows ionm exchange with extracellular fluid.

Osteoclasts

-Derived from fusion of monocytes and found in shallow depressions called howships lacunae- areas of osteoclast activity. -Osteoclasts are very large cells with 5-50 nuclei -are extensively branched and the cytoplasm of these cells stain acidophilic due to alot of mitochondria -have lots of lysosomes -these cells can be tested to determine if they are osteoclast because they will test in a acid phosphatase reaction -have lots of mitochondria and well developed RER and Golgi.

Endochondral ossification (indirect bone formation)

-Hyaline cartilage acts as a model this process has 2 phases. First there is hypertrophy and destruction of chondrocytes, and next there is these so called osteogenic buds that penetrate spaces left by degenerating chondrocytes and osteogenic cells to form osteoblast. So we are bringing blood capillaries and osteogenic cells into the destroyed space left empty to form osteoblasts.

Organic Component

-Main component is collagen type 1 and some collagen type 5. -Matrix also has ground substance in the the form of GAG's (chondrotin sulfate, keratan sulfate and hyaluronic acid). These form proteoglycans and proteoglycan aggregates. - the abundane of collagen type 1 causes the matrix to stain acidophilic, compared to cartilage that stains basophilic -several glycoproteins (osteocalcin, osteonectin, and osteopontin) and sialoproteins are present. These bind to the crystals, fibers, GS, and cells. Thus collagen and GS become mineralized to form bone

Hormonal Activity

-PTH which comes from the parathyroid gland stimulates osteoblasts to release osteoclast stimulating factor that increases the number and activity of osteoclasts which resorb bone >> break bone down to put its materials in the blood mainly calcium. This is due to low calcium. -Calcitonin from C cells of the thyroid gland acts on osteoclast directly by reducing osteoclast activity thereby inhibiting bone resorption. They act due to high levels of calcium in the blood. -Somatotropin (pituitary growth hormone) stimulates growth especially epiphyseal plates. Influences bone development via the liver which produces somatomedins (insulin like growth factor) which then stimulates the growth of the epiphyseal plates. Lack of this hormone results in dwarfism in children, and excess causes gigantism

Fracture repair

-Periosteal bone has to go back to hyaline cartilage then the primary bone will come in followed by secondary bone.

Microscopic classification of bone

-Primary bone is the first bone to form so seen in fetal development and bone repair. Abundant osteocytes and haphazard organization of collagen fibers causing the bone to be weak.. This bone is remolded and replaced by secondary bone except in tooth sockets, suture lines in skull, and insertion sites for tendons. -Secondary bone is the mature form of bone found in adults. This replaces primary bone. Contains parallel or concentric lamellae of collagen. Its matrix is calcifies (strong bone).

Ruffled border and clear zone

-Ruffled borders are the plasma membrane infoldings of osteoclast cells. -Clear zones are the abundant microfilaments that demarcates the bone area to be resorbed. -Bone resorption is the process by which osteoclasts break down bone and release the minerals, resulting in a transfer of calcium from bone fluid to the blood. 2 phases of resorption: 1.initial dissolution of Ca salts by organic acids from plasma membrane. 2. Subsequent enzymatic degradation of collagen by lysosomal enzymes such as collagenase and proteolytic enzymes.

Endochondral ossification (indirect bone formation)

-The primary ossification is in the middle of the bone a region called diaphysis. The perichondrium (cartilage) in this region becomes vascularized and chondrogenic cells become osteogenic cells. This a transition from cartilage precursor cells to bone precursor cells. These cells then transform to osteoblast and the perichondrium is now called periosteum. Understand that in this region bone formation occurs via intramembranous formation thus forming the subperiosteal bone collar. -Chondrocytes in this central region undego hypertrophy and this is follwed by cell death. The cartilage matrix becomes calcified cartilage and the lacunae become large marrow spaces. -The osteogenic bud enters the bone collar as a result of osteoclast activity and invaded the calcified cartilage. The osteogenic cells turn into osteoblasts in spaces left by dead chondrocytes. -Osteoblast lay down primary bone on top of the remnants of calcified cartilage forming the primary ossification center.The subperiosteal bone continues to form by intramembranous ossification. Osteoclast destroy the new bone and calcified cartilage. Lamellar bone is then laid down, and then blood vessels then invade the proximal epiphyseal cartilage to establish a secondary ossification center. A similar process occurs at the distal end resulting in epiphyseal plat of cartilage forming at each end.

Intramembraneous ossification (direct bone formation)

-Understand that bone grows only by appositional means. -Takes place in flat bones of skull and clavicle and face Mesenchyme cells > osteogenic cells > osteoblast > trabeculae of bone>primary bone> remoldelled > compact bone.

Vitamins

-Vit D absorption of Ca from small intestine. Deficiency results in poorly calcified bone yielding a condition called rickets. -Vit C is necessary for collagen formation and lack of it results in scurvy. -Vit A lack of this inhibits proper bone formation and growth. Excessive amounts results increased bone formation. Early ossification of epiphyseal plates.

Osteocytes

-are mature bone cells derived from osteoblasts that became trapped in lacuna within the calcified matrix. The whole purpose of these cells is to maintain the bone so if they leave the foundation is gone. -sticking out of the lacunae are canaliculi which are cytoplasmic extensions which connect with extensions of another cell in another lacunae. Via gap junction the cells can communicate with each other allowing movements of ions and small molecules. -extracellular fluid (nutrients and metabolites) are found within the canaliculi -Osteocytes are flat, almond shaped cells with reduced RER and Golgi -*are involved in maintenance of bone matrix by maintaining blood calcium levels. -death of these cells results in resorption of matrix> break down of bone

Cells of bone

4 Types: -Osteogenic same as osteoprogenitor -Osteoblast -Osteocyte -Osteoclast -Osteoprogenitor cells are derived form mesenchyme and can differentiate into osteoblasts. - are located in the inner cellular layer of periosteum lining the Haversian canals, and the endosteum which lines the marrow cavity -are flat, inconspicous cells with a pale staining oval nucleus and sparse cytoplasm which mean they are low in RE

More

Acromegaly- Excess GH in Adults - abnormal increase in bone formation without normal bone resorption. Bones of hands and face are thickened Osteopetrosis- genetic disorder affecting osteoclasts - can't resorb bone because cells have no ruffled border Osteoporosis- Low bone mass(density)- thin trabeculae and widen haversian canals - result- fragile bone *- increase bone resorption , decrease bone formation , or both Achondroplasia- is a defect of endochondral ossification (indirect bone formation) It is the most common form of inherited dwarfism-- have short limbs.

Joints

Joints : Bones that articulate or come close together at joints are classified into : A) Synarthroses- closely bound with minimal movement There are 3 types of synarthrosis 1) Synostosis: Skull bones 2) Synchondrosis: rib & sternum 3) Syndesmosis : pubic symphysis B) Diarthroses- bones are free to articulate over a wide range and these joints of extremities. Synovial membrane -2 cell types: Type A are macrophages. Type B cells are fibroblast - secrete the synovial fluid ( a plasma filtrate with lotsof hyaluronic acid and lubricin).

Mechanism of Bone Resorption

Phase 1: -Inside the osteoclast CO2 and water form carbonic acid via the enzyme carbonic anhydrase -it dissociates into H+ and HCO3- -HCO3- will link with Na+ and enter capillaries -H+ is transported into the ruffled border reducing the pH and acting on inorganic matrix of the bone. The H+ ions make the environment very acidic. This dissociates the calcium ions from the hydroxyapatite crystals. These release material enter the capillaries via osteoclasts. Phase 2: -lysosomal enzymes are released outside to act on organic materials of the now decalcified bone. -These organic fragments are further taken up and further broken down. -Bone resorption is the process by which osteoclasts break down bone and release the minerals, resulting in a transfer of calcium from bone fluid to the blood.

Bone Marrow

Red bone marrow is in sternum and ribs and epiphyses plates of long bones. Blood cell formation takes place here between trabeculae of spongy bone Yellow bone marrow is located in the diaphyseal cavity of long bones and stores fat.

More

Rickets - disease in infants and children - deficiency in Vit D; Can't absorb Ca from intestines - Disturbances in ossification of epiphyseal plate cartilage - result- poorly calcified bone matrix ; deformed bones of legs Osteomalacia -Adult rickets -Prolonged deficiency of Vit D - newly formed bone not properly calcified - Major problem in pregnancy because fetus requires Ca Scurvy - Deficiency of Vit C -Poor collagen production - Result- reduction in bone matrix formation and dev. -Healing is a problem -bleeding gums

Gross classification of bone

Spongy has numerous interconnecting cavities and osseus (bony) projections called trabeculae. Its matrix has irregular arrangements of lamellae. Compact bone is a solid mass with few intervening spaces. Has rigid outer shell which resists deformation.