Platelet-Rich Plasma Attenuates Knee Osteoarthritis in Rats via Modulation of Gut Microbiota.

Abstract

BACKGROUND: Platelet-rich plasma (PRP), a platelet and plasma concentrate extracted from whole blood via centrifugation, has multiple bioactive properties. However, its role in the progression of knee osteoarthritis (KOA) and the underlying mechanisms of action remain unclear. In this study, we investigated the therapeutic effects of PRP extracted from rat whole blood on the progression of KOA and assessed whether its mechanism involves modulation of the gut microbiota (GM). METHODS: Knee osteoarthritis (KOA) rat models were established by intra-articular injection of 1 mg of sodium monoiodoacetate (MIA) into the knee joints. The rats were administered intra-articular injections of 60 μL of PRP on days 15, 17, and 19 post-modeling. Moreover, we established pseudo-germ-free (pGF) KOA rat models and performed fecal microbiota transplantation (FMT) experiments to investigate whether the GM mediates the therapeutic effects of PRP on KOA. Therapeutic efficacy was assessed by conducting gait analysis, joint swelling measurement, and micro-CT scanning. The pathological changes were evaluated via Safranin O-Fast Green and hematoxylin-eosin (HE) staining, as well as immunohistochemistry (IHC). The alterations in the GM were evaluated by 16S rRNA gene sequencing. RESULTS: We found that PRP effectively improved abnormal gait patterns, reduced inflammation levels, alleviated subchondral bone loss, repaired the damaged articular surface, and mitigated cartilage destruction in KOA rats. Concurrently, PRP intervention restored intestinal barrier function and positively modulated the dysregulated composition of the GM. The pGF condition reversed the improvements induced by PRP in KOA rats, whereas transplanting GM from PRP-treated KOA rats to recipient KOA rats promoted recovery in the latter. CONCLUSION: This study demonstrated that PRP ameliorates KOA progression, at least partially, by modulating GM diversity (notably), enhancing intestinal barrier integrity, and reducing systemic inflammation.