基于OPG/RANKL/RANK信号通路探讨中医"血瘀"与膝骨关节炎OA

The osteoprotegerin(OPG)/receptor activator of NF-κB ligand(RANKL)/receptor activator of NF-κB(RANK)signa-ling pathway is an important pathway regulating bone resorption and bone remodeling,and is closely related to subchondral bone sclero-sis and osteophyte formation in knee osteoarthritis(KOA).In this pathway,OPG competitively binds to RANKL,blocking the interac-tion between RANKL and RANK,inhibiting osteoclast differentiation,proliferation,activation,and maturation,and inducing their apopto-sis,thereby regulating subchondral bone remodeling.Traditional Chinese medicine(TCM)considers blood stasis to be a key pathologi-cal mechanism of KOA,and clinical treatment based on the concept of"stasis"has been effective,but lacks molecular biological evi-dence.Promoting unobstructed microcirculation within bone,reducing high intraosseous pressure,improving blood coagulation status,and enhancing local blood flow are important directions for the prevention and treatment of this disease.Blood-activating and stasis-resol-ving Chinese medicines can protect joint cartilage by improving bone microcirculation disorders.Among them,kidney-tonifying and blood-activating Chinese medicines that regulate the OPG/RANKL/RANK signaling pathway have shown significant therapeutic effects and are worthy of in-depth study.Current research has certain shortcomings:previous studies have mostly focused on inflammatory cy-tokines in relation to cartilage damage while neglecting the important role of subchondral bone in disease development;although the OPG/RANKL/RANK system can explain the pathogenesis of KOA from the perspective of abnormal bone remodeling and provide a mo-lecular biological basis for the traditional Chinese medicine treatment theory of"blood stasis",the specific mechanisms remain unclear.In the future,molecular biology techniques should be utilized to conduct in-depth and systematic studies of this pathway,making it a new target for guiding the prevention and treatment of KOA with traditional Chinese medicine.