Dental Pulp Stem Cell-Derived Exosomes Alleviate Mice Knee Osteoarthritis by Inhibiting TRPV4-Mediated Osteoclast Activation

Osteoarthritis (OA) is a degenerative disease that causes chronic pain and joint swelling and even disables millions of patients. However, current non-surgical treatment for OA can only relieve pain without obvious cartilage and subchondral bone repair. Mesenchymal stem cell (MSC)-secreted exosomes have promising therapeutic effects on knee OA, but the efficacy of MSC-exosome therapy is not well determined, and the mechanisms involved are still unclear. In this study, we isolated dental pulp stem cell (DPSC)-derived exosomes by ultracentrifugation and determined the therapeutic effects of a single intra-articular injection of DPSC-derived exosomes in a mice knee OA model. The results showed that the DPSC-derived exosomes effectively improved abnormal subchondral bone remodeling, inhibited the occurrence of bone sclerosis and osteophytes, and alleviated cartilage degradation and synovial inflammation in vivo. Moreover, transient receptor potential vanilloid 4 (TRPV4) was activated during the progression of OA. Enhanced TRPV4 activation facilitated osteoclast differentiation, and TRPV4 inhibition blocked this process in vitro. DPSC-derived exosomes repressed osteoclast activation in vivo by inhibiting TRPV4 activation. Our findings demonstrated that a topical, single injection of DPSC-derived exosomes is a potential strategy for knee OA treatment, and that the exosomes regulated osteoclast activation by TRPV4 inhibition, which may act as a promising target for clinical OA treatment.

Automated summary

Osteoarthritis (OA) is a degenerative disease that causes chronic pain and joint swelling in millions of patients. Current non-surgical treatment for OA can only relieve pain, and the efficacy of mesenchymal stem cell (MSC)-secreted exosomes therapy is uncertain. In this study, dental pulp stem cell (DPSC)-derived exosomes were shown to effectively improve subchondral bone remodeling, inhibit bone sclerosis and osteophyte formation, and alleviate cartilage degradation and synovial inflammation in a mouse knee OA model. Furthermore, DPSC-derived exosomes repressed osteoclast activation by inhibiting TRPV4 activation. These findings suggest that a single injection of DPSC-derived exosomes may be a potential strategy for knee OA treatment and TRPV4 inhibition could be a promising target for clinical OA treatment.