✍ Scribed by Rebecca K. Studer; Constance R. Chu
No coin nor oath required. For personal study only.
These studies compare actions of p38 MAPK inhibition and COX2 inhibition to modulate human arthritic chondrocyte responses to TGF‐β and FCS under basal and IL‐1 activated conditions.
Chondrocytes isolated from arthritic human femoral condyle cartilage obtained at total knee replacement were grown to 80% confluence. Proteoglycan synthesis and proliferation were measured with and without IL‐1 activation in the presence and absence of growth factors and with and without inhibition of p38 MAPK or COX2 activity. Experiments to evaluate TIMP‐1 production under these conditions were done using cartilage organ cultures.
Neither p38 MAPK inhibitors nor COX2 inhibition affected basal proliferation. However both inhibitors enhanced the proliferative response to TGF‐β and FCS in IL‐1 activated chondrocytes. TGF‐β stimulated proteoglycan synthesis was decreased by p38 MAPK inhibition, however COX2 inhibition restored the response to TGF‐β in IL‐1 activated cells. In contrast, COX2 inhibition did not modulate TIMP‐1 production while p38 MAPK inhibitors potentiated TGF‐β stimulated production of TIMP‐1 in IL‐1 activated cartilage.
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. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
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