The role of the synovium and cartilage in the pathogenesis of beta(2)-microglobulin amyloidosis

The predilection for beta (2)-microglobulin (beta M-2) amyloid deposition i n articular structures is unique compared to other forms of amyloid; this a rticle focuses on possible pathogenic mechanisms. The synovium and/or carti lage appear to be important in the pathogenesis of beta M-2 amyloidosis (A beta M-2), as amyloid is not found in the shafts of long bones. The concent ration of beta M-2 in the joint fluid parallels that in serum. Once in the joint space, evidence suggests that the beta M-2 binds to collagen in carti lage as the initial site of deposition. This binding may serve as the first step in subsequent amyloid formation, although this remains to be proven. beta M-2 has been shown to have many direct effects on synovial fibroblasts , including induction of the release of cytokines, metalloproteinases, cycl ooxygenase-2, and vascular cell adhesion molecule-1 (VCAM-1). The release o f these inflammatory mediators that lead to tissue degradation is also obse rved in other forms of arthritis. Thus beta M-2 itself may elicit the relea se of inflammatory mediators from synovial fibroblasts even in the absence of cellular infiltrates.