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骨保护素(osteoprotegerin, OPG)/核因子κB受体活化因子配体(receptor activator of NF-κB ligand, RANKL)/核因子κB受体活化因子(receptor activator of NF-κB,RANK)信号通路是调节骨吸收及骨重建的重要通路，与膝骨关节炎(knee osteoarthritis, KOA)软骨下骨硬化、关节骨赘形成密切相关。该通路中，OPG通过与RANKL竞争性结合，阻断RANKL与RANK的相互作用，抑制破骨细胞的分化、增殖、活化与成熟，诱导其凋亡，从而调节软骨下骨重塑。中医认为血瘀是KOA的关键病机，临床从“瘀”论治疗效确切，但缺乏分子生物学依据。疏通骨内微循环淤滞、降低骨内高压、改善血凝状态、促进局部血运是防治该病的重要方向。活血化瘀中药可通过改善骨内微循环障碍保护关节软骨，其中通过调控OPG/RANKL/RANK信号通路发挥作用的补肾活血中药疗效显著，值得深入研究。当前研究存在以下不足：以往多从炎症细胞因子对软骨损伤的角度入手，忽视了软骨下骨在发病中的重要作用；OPG/RANKL/RANK系统虽可从骨重建异常角度解释KOA发病机制，并为中医“血瘀”论治提供分子生物学依据，但具体机制仍未阐明。未来应借助分子生物学技术，深入系统研究该通路，使其成为指导中医药防治KOA的新靶点。
Abstract：The osteoprotegerin(OPG)/receptor activator of NF-κB ligand(RANKL)/receptor activator of NF-κB(RANK) signaling pathway is an important pathway regulating bone resorption and bone remodeling, and is closely related to subchondral bone sclerosis and osteophyte formation in knee osteoarthritis(KOA).In this pathway, OPG competitively binds to RANKL,blocking the interaction between RANKL and RANK,inhibiting osteoclast differentiation, proliferation, activation, and maturation, and inducing their apoptosis, thereby regulating subchondral bone remodeling.Traditional Chinese medicine(TCM) considers blood stasis to be a key pathological mechanism of KOA,and clinical treatment based on the concept of "stasis" has been effective, but lacks molecular biological evidence.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-resolving 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 cytokines 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 molecular 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.
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基本信息:
DOI：10.16368/j.issn.1674-8999.2026.05.153
中图分类号:R274.9
引用信息:
[1]司元龙,陈志伟,申建军.基于OPG/RANKL/RANK信号通路探讨中医“血瘀”与膝骨关节炎[J].中医学报,2026,41(05):1031-1036.DOI:10.16368/j.issn.1674-8999.2026.05.153.
基金信息:
甘肃省中医药管理局科研项目(GZK-2018-31)
2024-11-27
2024-11-27
2024-11-27