RhoA/ROCK pathway: implication in osteoarthritis and therapeutic targets

Ras homolog gene family, member A (RhoA) and its downstream effector Rho-associated protein kinase (ROCK) play important roles in multiple cellular processes, but abnormal activation of this pathway have been reported to be involved in various types of diseases, including osteoarthritis (OA). This article focused to review the RhoA/ROCK association and its functional role in OA development, and possible therapeutics of OA by targeting this pathway. We have explored the databases like Pubmed, Google Scholar, Web of Science and SCOPUS, and collected the papers on Rho/ROCK and their relationship with OA, and reviewed comprehensively. Studies revealed that the abnormal activation of RhoA/ROCK signaling is involved in early phase response to abnormal mechanical stimuli, which is thought to be a contributory factor to OA progression. RhoA/ROCK interacts with OA pathological factors and induces cartilage degeneration through the degradation of chondrocyte extracellular matrix (ECM). As the RhoA/ROCK activity can affect bone formation by triggering cartilage degradation, it may represent a possible therapeutic target to treat OA. Interestingly, several pharmaceutical companies are investing in the development of RhoA/ROCK inhibitors for the treatment of OA. However, a few in vivo experiments have been successfully conducted to demonstrate the potential value of RhoA/ROCK pathway inhibition in the treatment of OA. This review provides an insight into the functional role of Rho/ROCK pathway, and indicates that targeting this pathway might be promising in future OA treatment.