Objective

To investigate the participation of osteoclast-like bone resorbing cells in the joint destruction of murine collagen induced arthritis (CIA).

Methods

After induction of CIA in DBA/1J mice, a histological time course study was conducted on paw sections stained for tartrate resistant acid phosphatase (TRAP), a marker of osteoclasts. Cells from arthritic paws were cultured in vitro with or without indomethacin (IM) or anti-interleukin 6 neutralizing antibody (anti-IL-6), and stained for TRAP. Levels of prostaglandin E2 (PGE2), IL-1beta, IL-6, and tumor necrosis factor-alpha in the culture supernatants were determined by ELISA. The bone resorbing ability of these cells was examined on dentine slices. In control experiments, cells of normal paws or of arthritic tibiae were cultured in the same manner.

Results

TRAP positive osteoclast-like cells were detected late in the development of bone lesions at every eroded front in the pannus-bone and the pannus-subchondral bone junctions of arthritic joints. In vitro, cells of arthritic paws formed bone resorbing osteoclast-like cells spontaneously. However, the control culture failed to form these cells. PGE2 and IL-6 were detected at higher levels in arthritic culture than in control culture. Although both indomethacin and anti-IL-6 reduced osteoclast-like cell formation and indomethacin inhibited PGE2 synthesis, indomethacin failed to reduce IL-6.

Conclusion

These findings suggest the direct participation of osteoclast-like cells in the joint destruction of CIA, the locally enhanced activity of osteoclast-like cell differentiation in arthritic paws, and the participation of prostaglandins and prostaglandin-independent IL-6 in this differentiation.