Joint contracture is a fibrotic complication induced by joint immobilization and trauma,which is characterized as excessive myofibroblast proliferation in joint capsule.The treatments of joint contracture are unsatisf...Joint contracture is a fibrotic complication induced by joint immobilization and trauma,which is characterized as excessive myofibroblast proliferation in joint capsule.The treatments of joint contracture are unsatisfied and patients are suffered from joint dysfunction.Our previous study has shown that curcumin can inhibit myofibroblast proliferation in vitro,but the major challenge is the low aqueous solubility and biological activity of curcumin.In this study,hyaluronic acid-curcumin(HA-Cur)conjugate was synthesized to suppress myofibroblasts in joint contracture.Cells were isolated from the joint capsules of joint contracture patients and induced to active myofibroblasts by transforming growth factor-b(TGF-b).The anti-fibrotic function and mechanisms of HA-Cur were investigated by immunohistochemistry,reverse transcription-quantitative polymerase chain reaction(PCR),methylation-specific PCR,western blot,transwell migration assay and proliferation assay.Results showed that 30 lM HA-Cur significantly attenuated the fibrotic functions of myofibroblast in joint contracture in vitro by regulating the methylation of prostaglandin E receptor 2(PTGER2)and inhibiting TGF-b signaling.This may provide a mechanism for the treatment of joint contracture,and provide a molecular target PTGER2 for therapy during the pathogenesis of joint contracture.展开更多
基金grants from National Natural Science Foundation of China[81772368 and 81802184]Natural Science Foundation of Guangdong Province[2017A030310226]+1 种基金the Guangdong Traditional Chinese Medicine Bureau Research Fund[20181061]Medical Research Foundation of Guangdong[A2017003].
文摘Joint contracture is a fibrotic complication induced by joint immobilization and trauma,which is characterized as excessive myofibroblast proliferation in joint capsule.The treatments of joint contracture are unsatisfied and patients are suffered from joint dysfunction.Our previous study has shown that curcumin can inhibit myofibroblast proliferation in vitro,but the major challenge is the low aqueous solubility and biological activity of curcumin.In this study,hyaluronic acid-curcumin(HA-Cur)conjugate was synthesized to suppress myofibroblasts in joint contracture.Cells were isolated from the joint capsules of joint contracture patients and induced to active myofibroblasts by transforming growth factor-b(TGF-b).The anti-fibrotic function and mechanisms of HA-Cur were investigated by immunohistochemistry,reverse transcription-quantitative polymerase chain reaction(PCR),methylation-specific PCR,western blot,transwell migration assay and proliferation assay.Results showed that 30 lM HA-Cur significantly attenuated the fibrotic functions of myofibroblast in joint contracture in vitro by regulating the methylation of prostaglandin E receptor 2(PTGER2)and inhibiting TGF-b signaling.This may provide a mechanism for the treatment of joint contracture,and provide a molecular target PTGER2 for therapy during the pathogenesis of joint contracture.
