p38 MAPK and COX2 inhibition modulate human chondrocyte response to TGF-β

p38 MAPK inhibition and COX2 inhibition have unique and similar abilities to counteract some of the effects of IL-1 on human chondrocyte/cartilage metabolism. Both will partially restore the proliferative response to growth factors. p38 MAPK inhibition blunts TGF-β stimulation of proteoglycan synthesis, but increases TIMP-1 synthesis. COX2 inhibition can restore the proteoglycan synthetic response to TGF-β, but has no effect on cartilage TIMP-1 production. Use of these inhibitors to minimize cartilage damage in arthritic and mechanically stressed joints should reflect these characteristics.