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.