Download The composition of the matrix in compact bone is the same as that in

Biochemistry & histology of connective tissue and matrix proteins
1. Outline the key features of the molecular structure of collagen which confer its important
biomechanical properties.
2. Know the different types of collagen found in connective tissues.
The extracellular matrix (ECM) fills the interstitial spaces and binds cells and tissue together. It
varies from soft fluid to rock hard. ECM varies with tissue but always contains 2 basic
components:
- proteoglycans (glycosaminoglycan – GAG – covalently bonded protein and CHO)
- insoluble protein fibres (collagen, elastin, fibronectin, laminin)
These insoluble fibres provide structure, strength, and anchor cells to matrix.
Collagen, the strongest and most abundant, is a group name for types of rope-like fibres that have
a linear structure consisting of repeating units. 19 types of collagen have been characterised, and
they are synthesised in the endoplasmic reticulum of blast cells (mainly fibroblasts). Collagen is
formed from three -peptide chains (the tropocollagen subunit) wound together in a triple helix,
and stabilised by hydrogen bonds. This uninterrupted triple helix molecule is approximately 300
nm in length and 1.5 nm in diameter – a cable-like structure that provides significant tensile
strength to skin, tendons, ligaments and other cartilaginous structures (as opposed to GAGs which
resist compression forces): tough, non-tearable, and flexible (Nb ‘tensile’ means cannot be
stretched without breaking). Collagen molecules are then arranged into collagen fibrils, which are
formed by staggering and overlapping the collagen molecules. The amino acid hydroxylysine is
responsible for stabilising the side-to-side packing of the chains into fibrils. Collagen fibres in a
particular lamella run in one direction while fibres in adjacent lamellae run in the opposite
direction: this alternating pattern is designed to withstand torsion stresses.
The types of collagen have been assigned roman numerals in order of their discovery, and this
nomenclature has no bearing on their function or tissue location. Collagen types I-V are
considered the major collagens, since they comprise 98% of the total connective tissue protein.
Type I Collagen
The most important bone protein is type I collagen, formed from two 1 peptide chains and one
2 peptide chain. It comprises up to 90% of the bodies collagen, particularly in bones, skin,
tendons, ligaments, cornea, intervertebral disks, dentine, arteries and granulation tissues.
They give tissues their mechanical strength and provide the major biomechanical scaffold for cell
attachment and anchorage of macromolecules. Many macromolecules such as integrins,
fibronectin, fibromodulin and decorin attach to type I collagen. They also interact with many
cells, such as fibroblasts, and with platelets during blood clotting. In bones and dentin type I
collagen is mineralised with hydroxyapatite crystals. They are remarkably strong, and can
withstand twisting and bending, but offer little resistance to compression.
Type-II collagen is the basis for articular cartilage and hyaline cartilage, type-III contained in
skin, blood vessels, and internal organs, type-IV is the major component of basal lamina.
3. Identify the role of collagen in bone mineralization and modeling.
The composition of the matrix in compact bone is the same as that in spongy bone. Collagen
type-I fibers provide an organic framework on which hydroxyapatite crystals can form, a process
known as mineralisation. These crystals form small plates and rods that are locked into the
collagen fibers at regular angles. The result is a protein–crystal combination that possesses the
flexibility of collagen and the compressive strength of hydroxyapatite crystals. Around 30% of
the weight of bone is contributed by collagen fibres. In essence, the collagen fibers in bone act
like the steel reinforcing rods, and the mineralised matrix acts like the concrete.
Process of bone modeling:
1. The bones of the skeleton are ‘laid out’ as a cartilage model in the foetus. An ossification
center appears in the fibrous connective tissue membrane, when centrally located mesenchymal
cells differentiate into osteoblasts.
2. Osteoblasts begin to synthesize & secrete collagen and other organic matrix constituents
(proteoglycans and glycosaminoglycans (GAGs)) in their rough endoplasmic reticulum, resulting
in the production of osteoid. A maturation phase occurs within a week where calcium phosphate
salts begin to precipitate in spaces in the 3D collagen conformation, a process known as
mineralisation. Osteoblasts within the matrix are trapped, and become osteocytes.
3. Accumulating osteoid is laid down between blood vessels in such a way that it forms a random
network, called trabeculae (woven) bone.
In addition to forming the bone matrix collagen aids in bone formation by its role in cartilage
formation. Cartilage is a precursor in the process of bone formation, either by membranous or
endochondral ossification, and hyaline cartilage surrounds the epiphyseal ends of long bones.