Integrin-mediated mechanotransduction in IL-1 beta stimulated chondrocytes.
Mechanical loading and interleukin-1 beta (IL-1 beta) influence the release of nitric oxide (*NO) and prostaglandin E2 (PGE2) from articular chondrocytes via distinct signalling mechanisms. The exact nature of the interplay between the respective signalling pathways remains unclear. Recent studies have shown that integrins act as mechanoreceptors and may transduce extracellular stimuli into intracellular signals, thereby influencing cellular response. The current study demonstrates that the application of dynamic compression induced an inhibition of *NO and an upregulation of cell proliferation and proteoglycan synthesis in the presence and absence of IL-1 beta. PGE2 release was not affected by dynamic compression in the absence of IL-1 beta but was inhibited in the presence of the cytokine. The integrin binding peptide, GRGDSP, abolished or reversed the compression-induced alterations in all four parameters assessed in the presence and absence of IL-1 beta. The non-binding control peptide, GRADSP, had no effect. These data clearly demonstrate that the metabolic response of the chondrocytes to dynamic compression in the presence and absence of IL-1 beta, are integrin mediated.
Chowdhury
T T
TT
Medical Engineering Division and IRC in Biomedical Materials, Department of Engineering, Queen Mary, University of London, Mile End Road, London, E1 4NS, UK. t.t.chowdhury@qmul.ac.uk
Appleby
R N
RN
Salter
D M
DM
Bader
D A
DA
Lee
D A
DA
D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism; D002417:Cattle; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D015232:Dinoprostone / Q000378:metabolism; D016023:Integrins / Q000378:metabolism / Q000502:physiology*; D007375:Interleukin-1 / Q000494:pharmacology*; D040542:Mechanotransduction, Cellular / Q000187:drug effects* / Q000502:physiology; D050279:Metacarpal Bones / Q000166:cytology; D009569:Nitric Oxide / Q000378:metabolism; D012685:Sepharose / Q000502:physiology; D013314:Stress, Mechanical; D013997:Time Factors
D016023:Integrins; D007375:Interleukin-1; D009569:Nitric Oxide; D012685:Sepharose; D015232:Dinoprostone