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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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