Schulze-Tanzil Gundula
Department of Anatomy and Cell Biology, Paracelsus Medical University, Nuremberg, Bavaria, Germany.
J Exp Pharmacol. 2021 Feb 11;13:101-125. doi: 10.2147/JEP.S237479. eCollection 2021.
Osteoarthritis (OA) therapy remains a large challenge since no causative treatment options are so far available. Despite some main pathways contributing to OA are identified its pathogenesis is still rudimentary understood. A plethora of therapeutically promising agents are currently tested in experimental OA research to find an opportunity to reverse OA-associated joint damage and prevent its progression. Hence, this review aims to summarize novelly emerging experimental approaches for OA. Due to the diversity of strategies shown only main aspects could be summarized here including herbal medicines, nanoparticular compounds, growth factors, hormones, antibody-, cell- and extracellular vesicle (EV)-based approaches, optimized tools for joint viscosupplementation, genetic regulators such as si- or miRNAs and promising combinations. An abundant multitude of compounds obtained from plants, environmental, autologous or synthetic sources have been identified with anabolic, anti-inflammatory, -catabolic and anti-apoptotic properties. Some ubiquitous signaling pathways such as wingless and Integration site-1 (Wnt), Sirtuin, Toll-like receptor (TLR), mammalian target of rapamycin (mTOR), Nuclear Factor (NF)-κB and complement are involved in OA and addressed by them. Hyaluronan (HA) provided benefit in OA since many decades, and novel HA formulations have been developed now with higher HA content and long-term stability achieved by cross-linking suitable to be combined with other agents such as components from herbals or chemokines to attract regenerative cells. pH- or inflammation-sensitive nanoparticular compounds could serve as versatile slow-release systems of active compounds, for example, miRNAs. Some light has been brought into the intimate regulatory network of small RNAs in the pathogenesis of OA which might be a novel avenue for OA therapy in future. Attraction of autologous regenerative cells by chemokines and exosome-based treatment strategies could also innovate OA therapy.
骨关节炎（OA）的治疗仍然是一个巨大的挑战，因为目前尚无病因性治疗方案。尽管已确定了一些导致OA的主要途径，但其发病机制仍未完全明了。目前，大量具有治疗前景的药物正在骨关节炎实验研究中进行测试，以寻找逆转OA相关关节损伤并阻止其进展的机会。因此，本综述旨在总结骨关节炎新出现的实验方法。由于所展示策略的多样性，这里仅能总结主要方面，包括草药、纳米颗粒化合物、生长因子、激素、基于抗体、细胞和细胞外囊泡（EV）的方法、用于关节粘弹性补充的优化工具、基因调节剂如小干扰RNA（siRNA）或微小RNA（miRNA）以及有前景的联合治疗。已鉴定出大量来自植物、环境、自体或合成来源的具有合成代谢、抗炎、抗分解代谢和抗凋亡特性的化合物。一些普遍存在的信号通路，如无翅型MMTV整合位点家族成员1（Wnt）、沉默调节蛋白、Toll样受体（TLR）、哺乳动物雷帕霉素靶蛋白（mTOR）、核因子（NF）-κB和补体，都参与了骨关节炎的发病过程，并受到这些化合物的影响。透明质酸（HA）几十年来一直在OA治疗中发挥作用，现在已经开发出新型HA制剂，其HA含量更高，通过交联实现了长期稳定性，适合与其他药物如草药成分或趋化因子联合使用，以吸引再生细胞。对pH值或炎症敏感的纳米颗粒化合物可作为活性化合物（如miRNA）的通用缓释系统。在OA发病机制中，小RNA的紧密调控网络已有所揭示，这可能是未来OA治疗的一条新途径。趋化因子吸引自体再生细胞以及基于外泌体的治疗策略也可能革新OA治疗。
