Abstract
The blocking effects of anti-inflammatory cytokines and osteoprotergerin (OPG) on tartrate resistant acid phosphatase (TRAP) synthesis by monocyte-macrophages (MDMs) were investigated. Human Monocytes were cultured on PE/collagen coverslips supplemented with 50 mL of conditioned media from implant revision membranes, and anti-IL-6, anti-TNF- or OPG was added. Cultured media were collected and the cells were lysed. Both the cell releasates and lysates were analyzed for TRAP activity. Statistical analysis showed significantly inhibition of TRAP with addition of anti-IL-6 or anti-TNF-, but no inhibition was seen with addition of OPG. Blocking of TRAP with anti-inflammatory cytokines could provide a potential therapeutic method of preventing TRAP-associated peri-prosthesis osteolysis.
To investigate the blocking effects of anti-inflammatory cytokines and osteoprotergerin (OPG) on monocyte-macrophage tartrate resistant acid phosphatase (TRAP) syhthesis.
Either anti-IL-6 or anti-TNF- significantly inhibits monocyte-macrophage TRAP synthesis in vitro.
Since TRAP has been related to bone resorption, blocking monocyte-macrophage TRAP synthesis would be beneficial for preventing peri-prosthesis osteolysis.
Monocyte isolations were performed using blood from healthy donors. The isolated monocytes were cultured in triplicate on PE/collagen coverslips supplemented with 50 uls of fresh culture media or conditioned media from implant revision membrane. Anti-IL-6, anti-TNF-, or OPG at a concentration of 2 μg/mL was added at time zero, day two and four. The culture media were completely replaced with no addition at twenty-four hours prior to termination at day seven. On the terminating day, conditioned media were collected and the cells were lysed. Both the cell lysates and releasates were analyzed for TRAP activity, and the cell lysates were also assayed for DNA contents. The TRAP activity measured was normalized to the DNA contents. Statistical analysis showed significantly inhibition of TRAP with addition of anti-IL-6 (p< 0.01, n=3) or anti-TNF- (p< 0.01, n=3), but no inhibition was seen with addition of OPG. TRAP is believed to be mainly secreted by monocyte-macrophages and osteoclasts and associated with bone resorption. Therefore, these results suggest that the peri-prosthesis osteolysis be unlikely via the OPG-OPGL osteoclast activation axis, but possibly through the inflammatory cytokine pathway. Blocking of TRAP with anti-inflammatory cytokines could provide a potential therapeutic method of preventing peri-prosthesis osteolysis.
Funding from the Arthritis Society.
Correspondence should be addressed to Cynthia Vezina, Communications Manager, COA, 4150-360 Ste. Catherine St. West, Westmount, QC H3Z 2Y5, Canada
