Transforming growth factor-β family and stem cell-derived exosome therapeutic treatment in osteoarthritis (Review)

Osteoarthritis (OA), although extensively researched, still lacks an effective and safe treatment. The only current treatment option available for advanced OA is joint replacement surgery. This surgery may pose the risks of persistent pain, surgical complications and limited implant lifespan. Transforming growth factor (TGF)-β has a crucial role in multiple cellular processes such as cell proliferation. Any deterioration in TGF-β signaling pathways can have an immense impact on OA. Owing to the crucial role of TGF-β in cartilage homeostasis, targeting it could be an alternative therapeutic approach. Additionally, stem cell-based therapy has recently emerged as an effective treatment strategy that could replace surgery. A number of recent findings suggest that the tissue regeneration effect of stem cells is attributed to the paracrine secretion of anti-inflammatory and chondroprotective mediators or trophic factors, particularly nanosized extracellular vesicles (i.e., exosomes). Literature searches were performed in the MEDLINE, EMBASE, Cochrane Library and PubMed electronic database for relevant articles published before September 2021. Multiple investigators have confirmed TGF-β3 as a promising candidate which has the chondrogenic potential to repair articular cartilage degeneration. Combining TGF-β3 with bone morphogenetic proteins-6, which has synergistic effect on chondrogenesis, with an efficient platform such as exosomes, which themselves possess a chondroprotective function, offers an innovative and more efficient approach to treat injured cartilage. In addition, multiple findings stating the role of exosomes in chondroprotection has also verified a similar fact showing exosomes may be a more favorable choice than the source itself. In the present review, the importance of TGF-β family in OA and the possibility of therapeutic treatment using stem cell-derived exosomes are described.