Читать книгу Fractures in the Horse - Группа авторов - Страница 30

Type I collagen is present in bone in the form of relatively long fibres. The manner in which these fibres are deposited, their orientation relative to each other and their pattern of mineralization determine the bone's microstructure and material properties. The relatively small amounts of type III and V collagens that are also present in the organic matrix modulate the structure of the fibrils formed by type I collagen.

Approximately 10% of osteoid consists of non‐collagenous proteins, including osteocalcin, osteonectin, osteopontin, fibronectin and bone sialoprotein II, BMPs, growth factors and an array of proteoglycans and glycosaminoglycans [19]. These molecules serve important functions in cell communication, which influence formation and resorption, in determining bonds within and between collagen fibres, which influence the spatial organization of the extracellular matrix, and in the mineralization process.

Type I collagen is formed through a combination of intra‐ and extracellular processes. Three polypeptide chains, each composed of around 1000 amino acids, are transcribed and bind intracellularly to form a triple helix with N‐(amino)‐ and C‐(carboxy)‐terminal non‐helical propeptides on the end of each procollagen chain. Procollagen is secreted via secretory granules into the extracellular space, where it undergoes further modification that includes cleavage of the N‐ and C‐terminal propeptides by procollagen peptidase to form tropocollagen. The resultant molecule is approximately 300 nm in length and is relatively rigid. Excision of the terminal propeptides allows the molecules to polymerize into fibrils, which are stabilized by covalent cross‐links between hydroxylysine and lysine residues. Chains of tropocollagen molecules pack together side by side to form fibrils. Adjacent molecules are precisely staggered by roughly quarter of their length (67 nm) relative to each other, and collinear molecules are separated by a gap of approximately 40 nm. Consequently, there is a periodic pattern with zones in the fibrils where there are gaps within the cross‐section and areas where there are not (Figure 2.9). This produces a striated effect that can be seen in electron micrographs of stained collagen fibrils. Each gap in the fibril is surrounded by around six tropocollagen molecules and forms a cavity approximately 1.4 nm wide and 40 nm long. Although it is easier to visualize the structure as linear arrays of tropocollagen, there is evidence that the molecules inside the fibril are actually twisted into a complex 3D structure [21].

Figure 2.9 Model of hierarchical structure of collagen fibrils. Three helical (two α₁ and one α₂) collagen molecules form a triple helix 300 nm long; these are assembled into a fibril containing a staggered array of helices with 40 nm gap between C and N termini of collinear helices. Gaps are aligned across the width of fibrils. Alongside each 40 nm wide ‘gap zone’ (white) is a zone 27 nm wide in which no gaps exist.

Source: Schwarcz et al. [20].

Licensed under CC BY 4.0.

There is evidence that difference in the quality of the collagenous matrix accounts for some of the variation in bone strength that is widely noted. Collagen molecules undergo a large number of complex post‐translational modifications, both within and outside the cell, which require action of several different enzymatic and non‐enzymatic processes. These are carefully orchestrated and when disrupted can have profound effects on the structural properties of bone. Furthermore, racemization and isomerization reactions are age‐related changes that occur spontaneously and result in conformational modifications within the molecules that alter their physical properties.