Bone Metabolism

Introduction

Bone is a dynamic tissue its 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.

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.

Molecular Biology of Bone

Bone

Bone cells

Bone matrix.

Bone Matrix

Have structural and regulating properties: help control the cell mediated processes.

Composition depends upon age, site, dietary history, and presence of diseases.

Bone matrix

Inorganic phase

Organic Components

Water

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.

Organic Phase

Constitutes about 25% 90 % is type 1 collagen 5-10% is non collagenous protiens. Osteocalcin, osteonectin, osteopontin, integrins, various growth factors, bone inductive proteins.

Type 1 collagen

Synthesised by osteoblasts 3 polypeptide chains of 1000AA Triple helix two 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.

Osteocalcin

Syn: bone gamma carboxyglutamic acid, Gla protien. Carboxylation converts this protien into a ca and mineral binder in 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.

Osteonectin

Secreted by osteoblasts and platellets Binds hydroxyapatite and collagen Helps in organisation of minerals within matrix framework.

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.

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.

Water

Water is impregnated within the mineral crystals.

Bone Cells

Principal Regulators of bone metabolism

Bone cells

Osteoblasts

Osteocytes

Osteoclasts

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 cell membrane 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.