Effects Of Low - Intensity Pulsed Ultrasound On The Expression Of Articular Chondrocytes In Rabbit Knee Osteoarthritis By Integrin - FAK - MAPK Chemical Conduction Pathway

Objective:To investigate the effect of low intensity pulsed ultrasound on ECM production via integrin-FAK-MAPK mechanochemical transduction pathyway in rabbit osteoarthritis chondrocytes.Methods:Forty-two2-2.5kg New Zealand white rabbits were choosed, thirty-six of them underwent anterior cruciate ligament transaction to made OA model,the others were the normal controls. The chondrocytes were isolated and cultured in vitro after four weeks and randomly divided into six groups named normal control group(NC), OA group(OA) and OA+LIPUS group(O+L)、OA+DMSO group(O+D), OA+GRGDSP group(O+G). OA+SB203580group(O+S). NC group and OA group without any treatment,O+G group and O+S group add integrin inhibitor GRGDSP or p38MAPK inhibitor SB203580respectively,O+D group as a control group only add DMSO(placebo), each group exposed to LIPUS or not respectively. These groups exposed to40mW/cm2LIPUS radiation for20min once a day. Cells were collected after six days and the type Ⅱ collagen, aggrecan, MMP-13, integin β1, p-FAK, p38, p-p38, p-ERK1/2, p-JNK protein expression were detected by Western blot.Results:①Compared with NC group, the expression of collagen type Ⅱ and aggrecan was significantly lower in OA and O+L group, with more significant decrease in OA group(P<0.01). Compared with OA group, expression was significantly higher in O+L group(P<0.05).②Compared with NC group,the expression of MMP-13was significantly higher in OA and O+L group,with more significant increase in OA group(P<0.01). Compared with OA group, expression was significantly lower in O+L group(P<0.01).③Compared with NC group,the expression of integrin β1was significantly higher in OA and O+L group, with more significant increase in O+L group(P<0.05). Compared with OA group, expression was significantly higher in O+L group(P<0.05).④Compared with NC group,the expression of p-FAK, p-p38, p-ERKl/2, p-JNK was significantly higher in OA group (P<0.05). Compared with OA group, the expression of p-p38, p-ERK1/2, p-JNK was significantly lower, but the expression of p-FAK was significantly higher in O+L group(P<0.05).⑤Compared with O+D group, type Ⅱ collagen expression was significantly increased (P<0.05), MMP-13expression and the phosphorylation level of p38(the ratio of p-p38/p38) was significantly decreased (P<0.05) in O+G group. The type-Ⅱ collagen and MMP-13expression and the phosphorylation level of p38had no significant change (P>0.05) after LIPUS treatment in O+G group.⑥Compared with O+D group, type Ⅱ collagen expression was significantly increased (P<0.05), MMP-13expression and the phosphorylation level of p38was significantly decreased (P<0.05) in O+S group. The type-Ⅱ collagen expression was significantly increased(P<0.05), MMP-13expression and the phosphorylation level of p38was significantly decreased (P<0.05) after LIPUS treatment in O+S group.Conclusions:LIPUS could inhibit the degradation of collagen type Ⅱ and aggrecan and inhibit the expression of MMP-13via integrin-FAK-MAPK mechanochemical transduction pathyway in OA chondrocytes.