The effects of cyclic mechanical strain and tumor necrosis factor alpha on the response of cells of the meniscus.
OBJECTIVE
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-alpha) 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-alpha.


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 0.5Hz. The synthesis of proteoglycan, protein, nitric oxide (NO), and prostaglandin E(2) 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 E(2), proteoglycan, and total protein in a manner that depended on strain magnitude. TNF-alpha increased the production of NO and total protein, but inhibited proteoglycan synthesis rates. TNF-alpha 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.
Fermor
Beverley
B
Department of Surgery, Division of Orthopaedic Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Jeffcoat
Devon
D
Hennerbichler
Alfred
A
Pisetsky
David S
DS
Weinberg
J Brice
JB
Guilak
Farshid
F
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D008592:Menisci, Tibial / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D011458:Prostaglandins E / Q000096:biosynthesis; D011506:Proteins / Q000378:metabolism; D011509:Proteoglycans / Q000096:biosynthesis; D013314:Stress, Mechanical; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D011458:Prostaglandins E; D011506:Proteins; D011509:Proteoglycans; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II