The effects of mechanical strain on synovial fibroblasts

Purpose: Arthritic diseases of the temporomandibular joint, such as rheumatoid arthritis and osteoarthritis, suggest that inflammatory mediators and metalloproteinases may play a role in their pathogenesis. Recent clinical evidence from physical therapy and other modalities has shown a significant decrease in temporomandibular joint symptoms in patients with early disease. This project examines the effect of mechanical strain on synovial fibroblasts' production of inflammatory mediators including prostaglandin E(2) (PGE(2)) and proteinases. Materials and Methods: An established synovial fibroblast cell line (HIG-82) was grown to confluency in modified Eagle's medium supplemented with 10% fetal calf serum. The monolayer of fibroblasts was then subjected to mechanical strain using the Flexercell Strain Unit (Flexcell International Corporation, McKeesport, PA) at 3 cycles per minute, with 10 seconds' elongation of up to 24% and 10 seconds of relaxation. Levels of PGE(2) were determined by radioimmunoassay using commercially available product and measured in nanograms per milliliter of supernatant. Proteinases collagenase, gelatinase, and stromelysin were measured by H(3) radioactive labeling of acidic anhydride to the specific substrate. Enzymatic proteolysis of the radiolabeled substrate was then measured in supernate as units per milliliter. Statistical analysis of all results was performed using Student's t test in triplicate. Results: PGE(2) levels of mechanically activated cells was 18.1 +/- 13.4 ng/mL, with control levels being 58.0 +/- 9.2 ng/mL. This is a statistically significant decrease, between strained and unstrained cells with P < .05. in control cells, proteinase activity that degrades collagen, gelatin, or casein was 4.27 +/- 1.5, 4.62 +/- 0.11, or 0.11 +/- 0.01 U/mL, respectively. Levels for mechanically strained cells were 3.99 +/- 1.90, 4.02 +/- 0.90, and 0.12 +/- 0.01 U/mL, respectively. These results show that there is a significant decrease in PGE(2) levels of synovial fibroblasts undergoing mechanical strain. Proteinases examined show no difference in levels between mechanically activated fibroblasts and their controls. Conclusion: This decrease in PGE(2) production in synovial fibroblasts could help elucidate the mechanism by which physical therapy, and in particular continuous passive motion, may decrease inflammatory mediators of the temporomandibular joint. (C) 2003 American Association of Oral and Maxillofacial Surgeons.