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    Physiology Moleculer ofBone

    ByGROUP III

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    O N E S

    Some bones are hollow and inside them is the redbone marrow from which our blood is formed.

    All bones are formed from CARTILAGE, exceptthe clavicle and some parts of the cranium.

    Bones begin to grow before children are born, and

    as growth takes place the CARTILAGE, whichforms the temporary skeleton, is hardened intobone by the addition of calcium.

    Bone growth begins in the centre of each bone.This is in the centre of the shaft. Growth takesplace upwards, downwards and around thecentral marrow cavity.

    Secondary growth appears at both ends

    CARTILAGE remains between the areas until

    bone growth is completed.

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    This process of development from cartilage to boneis known as OSSIFICATION

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    Stages of IntramembranousOssification

    An ossification center appears in the fibrousconnective tissue membraneBone matrix is secreted within the fibrousmembraneWoven bone and periosteum formBone collar of compact bone forms, and redmarrow appears

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    Stages of IntramembranousOssification

    Figure 6.7.1

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    Stages of IntramembranousOssification

    Figure 6.7.2

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    Stages of IntramembranousOssification

    Figure 6.7.3

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    Stages of IntramembranousOssification

    Figure 6.7.4

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    WHAT ARE THE FUNCTIONS OF THE BONESAND THE SKELETON ?

    1. MOVEMENT

    2. Muscles are attached to bone by tendons, and theseallow us to apply POWER and MOVEMENT.

    3. PROTECTION of vital organs.

    4. STORES CALCIUM which gives bones hardness.

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    Bone Structure

    Periosteum hard outer coveringCells for growth and repair

    Compact bone hard strong layer

    Bone cells, blood vessels, protein withCa and P

    Spongy bone at ends of longbones

    Has small open spaces to lightenweight

    Marrow cavity hollow in middleof long bones

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    Bone Development

    Initial skeleton of cartilage in infants

    Replaced with bone by osteoblasts

    More than 300 bones at birth fuse to 206

    Always growing and breaking downOsteoblasts form new bone cells

    Osteoclasts

    break bone cells downOsteocytes mature bone cells

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    Cellular and Molecular Mechanisms of BoneRemodeling

    Bone is a dynamic tissue that undergoes continual adaptionduring vertebrate lifeto attain and preserve skeletal size,shape, and structural integrity and to regulate mineralhomeostasis. Two processes, remodeling and modeling,underpin development and maintenance of the skeletalsystem. Bone modeling is responsible for growth andmechanically induced adaption of bone and requires that theprocesses of bone formation and bone removal (resorption),although globally coordinated, occur independently atdistinct anatomical locations.

    Bone remodeling is responsible for removal and repair ofdamaged bone to maintain integrity of the adult skeleton andmineral homeostasis.

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    Factors Affecting Bone Growth

    6-21

    NutritionVitamin D

    Necessary for absorption of calcium from intestinesInsufficient causes rickets and osteomalacia

    HormonesGrowth hormone from anterior pituitaryThyroid hormone required for growth of all tissuesSex hormones as estrogen and testosterone

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    Calcium Homeostasis

    6-22

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    Calcium Homeostasis

    CaHomeostasis

    PTH

    Estrogen

    Calcitonin

    Vit. D

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    PARATIROID HORMONE (PTH)

    PTH is synthesizedand secreted by theparathyroid gland

    The Chief Cells in theparathyroid gland arethe principal site ofPTH synthesis.It is THE MAJOR ofCa homeostasis inhumans.

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    PTH has three major

    effects:1) PTH directly stimulates

    bone resorption;2) PTH directly stimulates

    recovery of calcium inthe kidney/increasereabsorbtion of Ca 2+

    3) PTH stimulates theproduction of 1a,25-dihydroxy-Vitamin Dfrom its precursors.

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    Calciumregulates

    PTHsecretion

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    Moleculer Mechanism of PTH

    PTH1 RECEPTOR AT OSTEOBLASTCELL MEMBRAN

    Increase Ca 2+ inmatrix bone

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    Calcitonin Role

    Calcitonin is synthesizedand secreted by theparafollicular cells of thethyroid gland

    Calcitonin acts todecrease plasma Ca 2+ levels.

    While PTH and vitamin Dact to increase plasmaCa 2+ -- only calcitonincauses a decrease inplasma Ca 2+ .

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    The target cell for calcitonin is the osteoclast.Calcitonin acts via increased cAMPconcentrations to inhibit osteoclast motility andcell shape and inactivates them.

    The major effect of calcitonin administration is arapid fall in Ca 2+ caused by inhibition of boneresorption.

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    Vitamin DVitamin D is a lipid soluble hormone that binds toa typical nuclear receptor, analogous to steroidhormones.Because it is lipid soluble, it travels in the bloodbound to hydroxylated a -globulin.PTH stimulates vitamin D synthesis ---- PTHstimulates 1 a -hydroxylase

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    Vitamin D Syntetize

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    VITAMIN D ACTION

    The main action of 1,25-(OH) 2-D is to stimulateabsorption of Ca 2+ from the intestineVitamin D acts via steroid hormone like receptorto increase transcriptional and translationalactivityOne gene product is calcium-binding protein(CaBP)

    CaBP facilitates calcium uptake by intestinal cells

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    Vitamin D Actions on Bones

    Another important target for 1,25-(OH) 2-D is the bone.Osteoblasts, but not osteoclasts have vitamin Dreceptors.1,25-(OH) 2-D acts on osteoblasts which produce aparacrine signal that activates osteoclasts to resorb Ca ++

    from the bone matrix.1,25-(OH) 2-D also stimulates osteocytic osteolysis.

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    ESTROGEN

    Estrogen (E) deficiency causes both the early andlate forms of osteoporosis in postmenopausalwomen and contributes to the development ofosteoporosis in elderly men

    It is associated with large increases in boneresorption caused by :increased osteoclast (OC) numbers (due toenhanced OC formation and reduced OCapoptosis) and by increased OC activity

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    Mechanism of estrogen in bone

    limiting the size and number of osteoclast-mediated osteoclast apoptosis via TGF osteoclaststimulates osteoblastic stem cell to membetnukosteocalst suprresor osteoprotegerinrestrict the production and secretion of IL-6 thatdoes not stimulate the marrow monocytes and Tcells to produce TNF-alfa, which stimulatesosteoclast growth

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    Estrogen :Decreaseresponsiveness OCprekursors to RANKL,

    cause Osteoclastdeacresing

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    Homeostatic Imbalances

    RicketsDisease of children due to a lack of vitamin D.Calcium is not deposited in bones.Bones become soft.Bowing of the bones, and other deformities occur.

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    Homeostatic Imbalances

    Osteomalacia

    Rickets of adults. Due to a lack of vitamin D. Calcium is not deposited in the bones. Bones become brittle.

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    Homeostatic Imbalances

    OsteoporosisBone reabsorption is greater than bone deposition.Due to any of the following:

    Lack of estrogen in women.Lack of exercise to stress the bones. Inadequate intake of calcium and phosphorus.

    Abnormalities of vitamin D metabolism.Loss of muscle mass.

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