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Biology Articles » Biochemistry » Articular Cartilage Collagen: an irreplaceable framework? » Collagen ultrastructure

Collagen ultrastructure
- Articular Cartilage Collagen: an irreplaceable framework?

Collagen fibrils seen by transmission electron microscopy (TEM) in articular cartilage form a random, loose network compared with collagen in most other connective tissues. Patterns of preferred fibril orientation are evident, however (Chen and Broom, 1998). In the surface zone (0-2mm), the fibrils are thin and tend to run primarily parallel to the plane of the articular surface with some degree of preferred orientation in that plane. A greater range of fibril diameters is seen in the deeper zones, and the organization appears more random when viewed by TEM. In the radial zone of some joint regions, a preferred orientation of fibril bundles orthogonal to the surface can be seen by scanning electron microscopy, also visible by TEM in regions of pathologically softened cartilage (Chen and Broom, 1998). The arcade-like macro-architecture of collagen responsible for this zonal appearance described by Benninghoff (1925) appears, on scanning electron microscopy, to reflect a folding over of radial fibre bundles to lie in the plane of the surface in a series of layers or leaflets that makes up the tangential zone (Notzli and Clark, 1997). In mammalian articular cartilage, the primary polymer-forming components (collagens II, IX and XI) do not appear to alter dramatically in proportion between these macroscopic zones.

In finer detail, the fibrillar appearance of the mature tissue differs between the pericellular and the intercellular (interterritorial) matrix. Fibrils become coarser and more obviously banded, as seen by TEM, going farther from the chondrocytes (Lane and Weiss, 1975). The proportion of type IX (Poole et al., 1987) and type XI (Vaughan- Thomas et al., 2001) collagens is highest in the thinnest fibrils that form the pericellular basket, or the chondron described by Poole et al. (1987). Remodelling and maturation of thin, newly made fibrils presumably involves removal of collagens IX and XI, and/or their dilution by addition of new type II collagen. To what degree thin fibrils fuse laterally in the matrix versus growing by accretion of new monomers is unclear, although both processes are thought to occur (Hunziker et al., 1997; Holmes et al., 2001).


The collagen II/IX/XI heteropolymeric template

Many different types of collagen molecules are expressed in articular cartilage but the backbone polymeric template during development is a copolymer of collagens II, IX and XI (Table 1). Collagen IX molecules decorate the surface of type II collagen fibrils, particularly the thin fibrils forming the basket (chondron) around chondrocytes (Hagg et al., 1998). Seven cross-linking sites have been defined in the collagen IX molecule (Fig. 1). These interact with type II collagen and with other collagen IX molecules, presumably on the surface of fibrils as illustrated (Fig. 2) (Diab et al., 1996; Ichimura et al., 2000; Wu et al., 1992).

The cross-links are either trivalent pyridinolines or borohydride-reducible divalent structures formed on the lysyl oxidase pathway typical of collagen. In an extension of one potential packing model (Miles et al., 1988), the NC1/COL2 domain of collagen IX docks in the hole region of the fibril and the molecule folds back through its NC2 domain (Fig. 2). This arrangement allows all seven crosslinks (Fig. 1) to form between a single collagen IX molecule and the surface of a type II collagen polymer.

Collagen XI molecules are primarily cross-linked to each other in a head-to-tail manner, and are believed to form a template that constrains the lateral growth of the type II collagen hetero-fibril (Blaschke et al., 2000). Retained N-propeptide domains on collagen XI are thought to inhibit fibril lateral growth (Gregory et al., 2000). The N-telopeptide cross-linking lysines responsible for XI-to- XI cross-linking are located external to candidate metalloproteinase cleavage sites. Such cleavages could depolymerise collagen XI (Wu and Eyre, 1995), perhaps providing a mechanism for fibril maturation and remodelling. These findings can be interpreted if collagen XI forms a head-to-tail self-cross-linked filamentous template that initiates the growth of collagen II fibrils (Wu and Eyre, 1995).

Table II shows three examples of differential chain usage from the collagen V/XI family of gene products. The molecular variants appear to be associated with tissuespecific forms of fibril organization.

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