Synovial lining macrophages mediate osteophyte formation during experimental osteoarthritis

Abstract

Objective: In human osteoarthritis (OA), various forms of pathology are observed. Besides cartilage damage and fibrosis, neogenesis of bone, osteophyte formation, also occurs. Osteophytes are thought to limit joint movement and cause pain. The objective of this study was to investigate whether synovial macrophages are involved in osteophyte formation in experimental OA, and if they are, to study which mechanism may be involved.

Design: Experimental OA was induced by two intra-articular injections of collagenase on alternate days into murine knee joints. The role of synovial lining macrophages in this model was studied by selective removal of these cells prior to OA induction using clodronate liposomes. After 1 and 2 weeks, knee joints were dissected and examined (immuno)histologically.

Results: At days 7 and 14 after induction of OA, osteophyte formation and fibrosis were observed. Depletion of synovial macrophages resulted in spectacular reduction of osteophyte formation, 84% and 66%, respectively, at days 7 and 14. Fibrosis and synovial activation, measured by MRP8/14 expression, were also ameliorated (40-60%). In addition, production of growth factors (TGFbeta, BMP-2 and BMP-4) in the lining was largely prevented but production of these growth factors in deeper layers of the synovium and the periosteum did not differ from controls.

Conclusions: These results indicate the synovial macrophage to be a pivotal cell in the synovium mediating osteophyte formation and other OA-related pathology, like fibrosis, during experimental OA. Production of growth factors and induction of synovial activation by these cells may play a crucial role in this event.