The effects of low intensity pulsed ultrasound on expression of mechanochemical transduction pathway-related protein of integrin-focal adhesion kinase-mitogen-activated protein kinases in the chondrocytes of rabbits with knee osteoarthritis

Abstract

Objective To observe any effect of low intensity pulsed ultrasound (LIPUS) on the expression of integrin-focal adhesion kinase (FAK)-mitogen-activated protein kinase (MAPK) mechanochemical transduction pathway-related proteins in the chondrocytes of rabbits with knee osteoarthritis (OA).Methods Of the 18 New Zealand white rabbits selected for the study,twelve received knee anterior cruciate ligament transection to model OA.The remaining 6 rabbits served as normal controls.At the 4th week after modeling the rabbits were sacrificed and chondrocytes were isolated and cultured in vitro.All the cultured cells were randomly divided into three groups:a normal control group (NC),an OA model group (OA) and an OA model plus LIPUS group (OA + LIPUS).When the cells had been cultured to the 2nd passage,the NC group and OA group cells had received no treatment.The OA + LIPUS group cells were exposed to 40 mW/cm2 of LIPUS for 20 min,once a day for 6 days.The expression of collagen protein type Ⅱ,aggrecan,MMP-13,integrin β1 p-FAK and p-p38,p-ERK1/2 and p-JNK Mapks were detected by Western blotting.Results Compared with the NC group,the expression of collagen type Ⅱ and aggrecan was significantly lower in the OA and OA + LIPUS groups,with more significantly lower expression of collagen type Ⅱ and aggrecan in the OA group than in the OA + LIPUS group.Compared with the NC group,the expression of MMP-13 was significantly higher in the OA and OA + LIPUS groups,with a significantly larger increase in the OA group.Compared with the NC group,the expression of integrin β1 and p-FAK was also significantly higher in the OA and OA + LIPUS groups,with a significantly larger increase in the OA + LIPUS group.Compared with the NC group,the expression of p-p38,p-ERK1/2 and p-JNK was also significantly higher in the OA group,but compared with the OA group,the expression of those kinases was,on average,significantly lower in the OA + LIPUS group.Conclusions LIPUS can inhibit the degradation of collagen type Ⅱ and aggrecan,and inhibit the expression of MMP-13,p-p38,p-ERK1/2 and p-JNK in OA chondrocytes,at least in vitro.At the same time,LIPUS can increase the expression of integrin β1 and p-FAK.The results show that LIPUS may activate an integrin-FAK-MAPK mechanochemical transduction pathway to induce changes in the extracellular matrix of chondrocytes. Key words: Ultrasound ; Chondrocytes; Integrin; Focal adhesion kinase ; Mitogen-activated protein kinases