Cyclic tensile strain suppresses catabolic effects of interleukin-1 beta in fibrochondrocytes from the temporomandibular joint

Objective. To discern the effects of continuous passive motion on inflamed temporomandibular joints (TMJ). Methods. The effects of continuous passive motion on TMJ were simulated by exposing primary cultures of rabbit TMJ fibrochondrocyte monolayers to cycl ic tensile strain (CTS) in the presence of recombinant human interleukin-1 beta (rHuIL-1 beta) in vitro. The messenger RNA (mRNA) induction of rHuIL-1 beta response elements was examined by semiquantitative reverse transcript ase-polymerase chain reaction. The synthesis of nitric oxide was examined b y Griess reaction, and the synthesis of prostaglandin E-2 (PGE(2)) was exam ined by radioimmunoassay. The synthesis of proteins was examined by Western blot analysis of the cell extracts, and synthesis of proteoglycans via inc orporation of S-35-sodium sulfate in the culture medium. Results. Exposure of TMJ fibrochondrocytes to rHuIL-1 beta resulted in the induction of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (C OX-2), which were paralleled by NO and PGE(2) production. Additionally, IL- 1 beta induced significant levels of collagenase (matrix metalloproteinase 1 [MMP-1]) within 4 hours, and this was sustained over a period of 48 hours . Concomitant application of CTS abrogated the catabolic effects of IL-1 be ta on TMJ chondrocytes by inhibiting iNOS, COX-2, and MMP-1 mRNA production and NO, PGE(2), and MMP-1 synthesis. CTS also counteracted cartilage degra dation by augmenting expression of mRNA for tissue inhibitor of metalloprot einases 2 that is inhibited by rHuIL-1 beta. In parallel, CTS also countera cted rHuIL-1 beta -induced suppression of proteoglycan synthesis. Neverthel ess, the presence of an inflammatory signal was a prerequisite for the obse rved CTS actions, because fibrochondrocytes, when exposed to CTS alone, did not exhibit any of the effects described above. Conclusion. CTS acts as an effective antagonist of rHuIL-1 beta by potentia lly diminishing its catabolic actions on TMJ fibrochondrocytes. Furthermore , CTS actions appear to involve disruption/regulation of signal transductio n cascade of rHuIL-1 beta upstream of mRNA transcription.