Expression of a wide range of fibrocartilage molecules at the entheses of the alar ligaments - possible antigenic targets for rheumatoid arthritis?

Objective: To provide evidence for the existence of a wide range of molecules characteristic of fibrocartilage at normal alar ligament entheses, that may have a bearing on the pathogenesis of rheumatoid arthritis. The alar ligaments provide the mechanical restraint for head rotation and their integrity can be compromised in patients with RA and occasionally in those with spondyloarthropathy.

Methods: Both alar ligaments from 6 cadavers were fixed in 90% methanol and cryosectioned longitudinally. Sections were immunolabelled with antibodies against collagens, glycosaminoglycans, and proteoglycans. The immunohistochemical data were related to estimates of insertional angle change at the entheses that were calculated from measurements of ligament length and dens diameter.

Results: Molecules typical of fibrocartilage (including type II collagen, link protein, and aggrecan) were found at both entheses, but labelling was more prominent at the odontoid end. This correlated with a 3-fold greater insertional angle change during 40 degrees of head rotation at the attachment of the ligament to the dens. At the odontoid enthesis, fibrocartilage differentiation was most conspicuous posteriorly.

Conclusion: The changes in insertional angle mean that compressive forces are prominent at both entheses, but particularly at the odontoid end, where the ligament partly wraps around the dens during head rotation. Thus, mechanical conditions are created that lead to pronounced fibrocartilage development, hence the expression of type II collagen, link protein, and aggrecan. The prominence of these molecules at the entheses raises the possibility that they could be antigenic targets for an autoimmune response in rheumatic diseases.