skeletal metabolism
TRANSCRIPT
-
7/30/2019 SKELETAL METABOLISM
1/17
Bone Metabolism
-
7/30/2019 SKELETAL METABOLISM
2/17
Introduction
Bone is a dynamic tissueits internal shape and
structure changing from moment to moment in
concert with the normal variation in mechanical
function and mineral exchange.
Has biomechanical role in locomotion
Essential for maintenance of mineral
homeostasis.
-
7/30/2019 SKELETAL METABOLISM
3/17
Birds view
Molecular biology of bone
Bone mineralisation
Bone metabolism / Remodelling Bone mineral metabolism
Factors responsible for bone mass regulation
Brief overview of metabolic bone disorder.
-
7/30/2019 SKELETAL METABOLISM
4/17
Molecular Biology of Bone
Bone
Bone cells Bone matrix.
-
7/30/2019 SKELETAL METABOLISM
5/17
Bone Matrix
Have structural and regulating properties: help
control the cell mediated processes.
Composition depends upon age, site, dietary
history, and presence of diseases.
-
7/30/2019 SKELETAL METABOLISM
6/17
Bone matrix
Inorganic phase Organic Components Water
-
7/30/2019 SKELETAL METABOLISM
7/17
Inorganic Phase
70 % of matrix
Ca phosphate analogous to crystalline ca
hydroxyapatite. Ca10 (Po4)6 (OH)2.
20 to 80 nm long, 2 to 5nm thick
Small amount of impurities in the form of carbonates in
[Po4]6, Cl-, and F- replacing (OH)2.
K+, Mg++, Sr++ etc will replace Ca. These impurities alter the physical property of bone.
-
7/30/2019 SKELETAL METABOLISM
8/17
-
7/30/2019 SKELETAL METABOLISM
9/17
Type 1 collagen
Synthesised by osteoblasts
3 polypeptide chains of 1000AA
Triple helixtwo identical alpha1 chains and one
aplha2 chain stabilised by hydrogen bonds. Linear molecule, allinged in parellel fashion with the
next molecule.
Pores present betwn the two bundles called hole
zones. Non collagenous protiens, and minerals get deposited
here.
-
7/30/2019 SKELETAL METABOLISM
10/17
Osteocalcin
Syn: bone gamma carboxyglutamic acid, Gla protien.
Carboxylation converts this protien into a ca and mineral binderin matrix.
Constitutes 10 % of non collagenous protiens.
Carboxylation of this protein is Vit K dependent.
Synthesis enhanced by VitD, Inhibited by PTH, and steroids.
Excreted in non metabolised form in urine.
Can be used as marker for bone formation/ resorption diseases.
Function:
Attracts osteoclasts to the site of bone resorption
Regulates rate of mineralisation and accretion of mineral crystals.
-
7/30/2019 SKELETAL METABOLISM
11/17
Osteonectin
Secreted by osteoblasts and platellets
Binds hydroxyapatite and collagen
Helps in organisation of minerals within matrixframework.
-
7/30/2019 SKELETAL METABOLISM
12/17
Integrins
Osteopontin, sialoprotiens, fibronectins etc
form a part of family of cell membrane proteins
called as integrins
These integrins anchor the bone cells to matrix.
-
7/30/2019 SKELETAL METABOLISM
13/17
Growth Factors
Transforming GF beta TGF B
Insulin dependent GF, IGF
IL1, 6 BMP 1-6.
All the above imp in regulating cell
differentiation, activation, growth and turnover.They are the coupling factors that link bone
formation and resorption.
-
7/30/2019 SKELETAL METABOLISM
14/17
Water
Water is impregnated within the mineral crystals.
-
7/30/2019 SKELETAL METABOLISM
15/17
Bone Cells
Principal Regulators of
bone metabolism
Bone cells
Osteoblasts Osteocytes Osteoclasts
-
7/30/2019 SKELETAL METABOLISM
16/17
Osteoblasts
Bone forming cells
formed from osteoprogenator cell lines of mesenchymal origin
Has single polarised nuclei.
Produces matrix proteins
Alkaline phosphatase is produced and distributed in cellmembrane
There will always be a newly formed unmineralised bone matrix[osteoid] around osteoblast.
Thus its a cell that produces type 1 collagen, responsive to PTH,and produces osteocalcin when stimulated by Vit D.
-
7/30/2019 SKELETAL METABOLISM
17/17