Esfuerzo mecánico cíclico y factor alfa de necrosis tumoral en cs. de menisco.

Beverley Fermor Ph.D.†, Devon Jeffcoat B.S.†, Alfred Hennerbichler M.D.†, ‡, David S. Pisetsky M.D., Ph.D.§, J. Brice Weinberg M.D.§ and Farshid Guilak Ph.D.†.

†Department of Surgery, Division of Orthopaedic Surgery, Duke University Medical Center, Durham, NC 27710, USA ‡Department of Trauma Surgery and Sports Medicine, Innsbruck Medical University, A-6020 Innsbruck, Austria §Department of Medicine, VA and Duke Medical Centers, Durham, NC 27705, USA

Summary

Objectives
Cells of the knee meniscus respond to changes in their biochemical and biomechanical environments with alterations in the biosynthesis of matrix constituents and inflammatory mediators. Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine that is involved in the pathogenesis of both osteoarthritis and rheumatoid arthritis, but its influence on meniscal physiology or mechanobiology is not fully understood. The objectives of this study were to examine the hypothesis that cyclic mechanical strain of meniscal cells modulates the biosynthesis of matrix macromolecules and pro-inflammatory mediators, and to determine if this response is altered by TNF-α.

Methods
Cells were isolated from the inner two-thirds of porcine medial menisci and subjected to biaxial tensile strain of 5–15% at a frequency of 0.5 Hz. The synthesis of proteoglycan, protein, nitric oxide (NO), and prostaglandin E2 were determined.

Results
Cyclic tensile strain increased the production of nitric oxide through the upregulation of nitric oxide synthase 2 (NOS2) and also increased synthesis rates of prostaglandin E2, proteoglycan, and total protein in a manner that depended on strain magnitude. TNF-α increased the production of NO and total protein, but inhibited proteoglycan synthesis rates. TNF-α prevented the mechanical stimulation of proteoglycan synthesis, and this effect was not dependent on NOS2.

Conclusions
These findings indicate that pro-inflammatory cytokines can modulate the responses of meniscal cells to mechanical signals, suggesting that both biomechanical and inflammatory factors could contribute to the progression of joint disease as a consequence of altered loading of the meniscus.