The cartilage collagens: a review of their structure, organization, and role in the pathogenesis of experimental arthritis in animals and in human rheumatic disease

Abstract

This contribution reviews the structure and organization of collagen molecules found in cartilage and the roles that they may play in rheumatic diseases. Cartilage is unique in its physical properties and molecular composition, and contains sufficient amounts of types II, IX, X, and XI collagen to deem these molecules as "cartilage-specific." The vitreous body of the eye, a "cartilage-like" tissue is also rich in the same collagens but is type X deficient. Types VI and XII collagen are present in cartilage as well as noncartilaginous tissues. Types II, IX, and XI collagen are organized into matrix fibrils, where type II constitutes the bulk of the fibril, type XI regulates fibril size, and type IX facilitates fibril interaction with proteoglycan macromolecules. Genetic defects in these collagens can produce mild to severe developmental abnormalities, including spondyloepiphyseal dysplasia often accompanied by an accelerated form of osteoarthritis. Sensitization with collagen can produce experimental rheumatic diseases. Type II collagen induces an erosive polyarthritis in certain strains of rats, mice, and higher primates which can resemble rheumatoid arthritis and relapsing polychondritis. Type XI collagen is arthritogenic in rats but not mice; type IX induces autoimmunity in both species but not arthritis. Arthritis is initiated by complement fixing antibodies that bind to type II collagen in autologous cartilage, and the production of these antibodies is MHC restricted and T cell dependent. It is unclear whether T cells alone can induce arthritis, although they probably help sustain it. Mapping and characterizing the of T cell epitopes on type II collagen has resulted in the synthesis of small homolog and substituted peptides of type II collagen which suppress arthritis in an antigen-specific manner by a variety of routes, including mucosal. Moreover, collagen-induced arthritis has proven a valuable model to study the contribution of cytokines and other biological agents in the pathogenesis of joint injury and how they might be used to develop new therapies. Collagen autoimmunity has been implicated in the pathogenesis rheumatoid arthritis and polychondritis. Circulating antibodies to type II collagen are found in both diseases. Antibodies to types IX and XI collagen are also present in rheumatoid sera but are less prevalent. Rheumatoid cartilage and synovium contain antibodies to type II collagen at a prevalence far greater than serum, suggesting an intra-articular antigen-driven immune process. Although effective in animal models, attempts to treat rheumatoid arthritis with orally administered type II collagen have proven elusive. Different approaches using newer formulations and selected or modified oligopeptides remain to be tested and could prove effective in the treatment of the human rheumatic diseases.

The impact of glycosylation on HLA–DR1–restricted T cell recognition of type II collagen in a mouse model

“…Type II collagen (CII; ␣1 [II]3) forms the backbone of the heteropolymeric fibrils that constitute 80-85% of the total collagen content of articular cartilage (1). Several lines of evidence suggest that CII is a candidate autoantigen in RA.…”

WISP3‐dependent regulation of type II collagen and aggrecan production in chondrocytes

“…Cartilage is a specialized connective tissue containing a large amount of ECM composed of a dense network of collagen fibers and a high concentration of proteoglycans, which provide the tissue with its ability to withstand compression and shear stress (12,13). Cartilage ECM is formed and maintained by chondrocytes (12)(13)(14)(15).…”

Nanoscale Imaging of Collagen Gels with Focused Ion Beam Milling and Scanning Electron Microscopy

“…Type I collagen is also the predominant load-bearing protein within connective tissues such as ligament, tendon, and the dermis (4)(5)(6). Type II collagen is the primary constituent of articular cartilage, while type III collagen forms granular tissue during wound healing and colocalizes with other collagens (7)(8)(9)(10). Fibrillar collagens undergo an entropy-driven process known as fibrillogenesis, in which single tropocollagen monomers self-assemble into nanoscale collagen fibrils with a high aspect ratio.…”