Mechanical loading and cartilage physiology
Whilst mechanical impact is known to be essential for cartilage maintenance, it\ud has been noted that altered joint loading and increased force may lead to cartilage\ud degradation and increase the risk for the development of osteoarthritis (OA). This\ud study investigated the cellular responses of chondrocytes to mechanical impact,\ud and the effects of possible chondroprotective agents for OA preventative\ud strategies in individuals exposed to high impact, repetitive loading. Single-impact\ud mechanical trauma (force 1.14 N, pressure 6.47 KPa) was determined to induce\ud biphasic decrease in cell volume to 647.38±60.38 ?m3 at 2 h and 516.52±38.86\ud ?m3 at 48 h, the initial phase of which was observed to be an active\ud mechanotransduction mechanism, termed Impact-Induced Volume Decrease\ud (IIVD), and the subsequent phase to be Apoptotic Volume Decrease (AVD). The\ud newly defined IIVD was concluded to be dependent upon the PKC/PLC?3\ud pathway, and possibly mediated by intracellular Ca2+ store release and Volume\ud Sensitive Organic Anion Channel (VSOAC) activity. Furthermore, mechanical\ud impact was observed to induce a rapid decrease in F-actin from 1.19±0.13 MU to\ud 0.87±0.02 MU, termed Impact-Induced Actin Decrease (IIAD) and associated with\ud the biphasic rise in cell death at rates of 2.75±0.41 %.h-1 and 0.66±0.03 %.h-1.\ud Both in vivo exercise and in vitro mechanical load induced a release IL-1?\ud (20.67±2.58 % and 5.86±0.21 AU), MCP-1 (25.69±0.53 % and 1.45±0.01 AU) and\ud IL-10 (8.97±2.40 % and 5.55±0.28 AU), with in vivo concentrations correlating with\ud joint magnitude and strike patterns. Decreased levels of IL-1? and MCP-1 (to\ud 9.60±2.34 % and 9.01±2.34 %, respectively) observed in the evening were further\ud confirmed using a hyperosmotic-treated in vitro model of prolonged static-loaded\ud cartilage with evidence for a IL-1?-dominated paracrine loop between articular\ud cartilage and mononuclear phagocytes. In vitro, chondroprotective and antiinflammatory\ud actions of chondroitin sulphate, glucosamine sulphate, REV 5901\ud and Tamoxifen were associated with a reduction in pre-impact cell volume\ud (average of 31.91±4.19 %) and increased pre-impact actin levels (average of\ud 39.92±9.29 %). Anti-inflammatory agents, curcumin and dexamethasone exhibited\ud less effective chondroprotective actions, via inhibition of IL-1? (average of\ud 83.45±1.30 %) and thus apoptosis. To conclude, high impact exercise is\ud recommended with a place for chondroprotective properties of chondroitin,\ud glucosamine sulphate and/or curcumin in high-risk groups before OA onset.