Experimental therapeutics for the treatment of osteoarthritis

Abstract

Osteoarthritis (OA) therapy remains a large challenge since no causative treat- ment 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)-kB 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.