Abstract
Mesenchymal stem cell (MSC)–based articular regeneration might be beneficial for both protecting and rebuilding cartilaginous tissues in the management of rheumatoid arthritis. However, it is unclear how current immunosuppressive strategies influence the multipotency of MSCs. The present study was undertaken to profile the direct effectiveness of major antirheumatic drugs including methotrexate, prednisolone, adalimumab, and tocilizumab on the multipotency of MSCs, with a special focus on chondrogenesis. The inhibitory effects of methotrexate on adipogenesis, osteogenesis, and chondrogenesis were observed to occur in a dose-dependent manner in an in vitro differentiation system. Prednisolone enhanced adipogenesis, but reduced alkaline phosphatase activity in osteoprogenitors and suppressed the formation of chondrospheroids. Adalimumab suppressed alkaline phosphatase activity, while tocilizumab diminished osteogenesis and chondrogenesis of MSCs in vitro. Chondrogenesis of antirheumatic drug-treated MSCs was also evaluated in vivo using a scaffolded spheroid-engrafted murine model. The biologics examined appeared to be relatively safe for cartilaginous formation, but methotrexate and prednisolone exhibited opposing influences on chondrogenesis. Taken together, these results reveal the direct efficacy of major antirheumatic agents on the multipotency of MSCs. Therefore, our findings suggest that optimization of medication protocols is further required for therapeutic approaches involving cartilaginous tissue engineering.
Highlights
Rheumatoid arthritis (RA) is characterized by persistent and chronic synovitis in the joint, followed by spontaneous progressive joint destruction, which is evident on X-ray as erosion and progressive narrowing of joint spaces (Sharp et al, 1985)
According to the titration curves, FABP4 expression in methotrexate-treated Mesenchymal stem cell (MSC) decreased in a dose-dependent manner with an EC50 of 54.53 nM, whereas prednisolone exhibited a slightly inhibitory effect on FABP4 induction (Figure 1B)
Direct application of adalimumab or tocilizumab did not elicit any effect on FABP4 expression in MSCs (Figure 1C)
Summary
Rheumatoid arthritis (RA) is characterized by persistent and chronic synovitis in the joint, followed by spontaneous progressive joint destruction, which is evident on X-ray as erosion and progressive narrowing of joint spaces (Sharp et al, 1985). Because joint destruction directly causes joint pain and functional disability, the basic strategy of RA management is altering the systemic immune status to prevent or delay joint destruction. After a prolonged period of time, the damage is almost irreversible and very limited options remain other than trying to prevent further destruction of the joint and considering prosthetic replacement arthroplasty. Treatment with disease-modifying antirheumatic drugs (DMARDs) has achieved outstanding results for systemic inflammatory management. Even when clinical remission is achieved, cartilage damage may continue to progress. With this in mind, approaches to protect against structural damage and repair existing damage have emerged for joint regeneration
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
