Effects of Platelet-Rich Plasma on Chondrocyte Senescence and Knee Osteoarthritis Progression

BACKGROUND: Knee osteoarthritis (KOA) is a common degenerative disease characterized by cartilage degradation and damage. Chondrocyte senescence plays a key role in disease progression, as the accumulation of senescent cells disrupts cellular function and exacerbates cartilage damage. Platelet-rich plasma (PRP), rich in growth factors, promotes tissue repair and regeneration. It remains unclear whether platelet-rich plasma modulates cellular senescence to regulate the progression of knee osteoarthritis. PURPOSE: To evaluate the effects of PRP on chondrocyte senescence in KOA and investigate its potential underlying mechanisms. STUDY DESIGN: Controlled laboratory study. METHODS: Chondrocyte cell cycle, senescence markers, senescence-associated secretory phenotype secretion, and extracellular matrix integrity were evaluated by Western blot, real-time quantitative polymerase chain reaction, flow cytometry, immunofluorescence, and β-galactosidase staining. Mitochondrial function and antioxidative properties were assessed by measuring mitochondrial membrane potential and reactive oxygen species levels. Additionally, a rat KOA model was established by anterior cruciate ligament transection, followed by weekly intra-articular injections of PRP or phosphate-buffered saline for 4 weeks. Knee joint samples were collected at 8 and 12 weeks after surgery for gross morphology, imaging, and histological analysis. RESULTS: In vitro experiments revealed that PRP inhibited chondrocyte senescence and extracellular matrix degeneration, as evidenced by increased expression of collagen type 2 alpha 1 (COL2A1) and aggrecan (ACAN), and decreased expression of matrix metalloproteinase 13 (MMP13), a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5), cyclin-dependent kinase inhibitor 2A (P16), cyclin-dependent kinase inhibitor 1A (P21), and tumor protein p53 (P53). Additionally, messenger ribonucleic acid (mRNA) expression of interleukin-1β (Il1b), interleukin-6 (Il6), and tumor necrosis factor (TNF), as well as β-galactosidase positivity, was suppressed. Furthermore, PRP was found to modulate cell cycle arrest, improve mitochondrial function, and enhance antioxidative properties. In vivo experiments demonstrated that intra-articular PRP injection repaired damaged articular cartilage, improved trabecular bone parameters, and upregulated the expression of COL2A1 and ACAN, while suppressing the expression of senescence-related proteins P16, P21, and P53 in the cartilage of the KOA model. CONCLUSION: Our results demonstrated that PRP may slow osteoarthritis progression by inhibiting chondrocyte senescence. CLINICAL RELEVANCE: Chondrocyte senescence plays a critical role in the pathogenesis of osteoarthritis. This study provides new theoretical foundations and experimental support for the clinical application of PRP in the treatment of osteoarthritis.