Improving the symptoms of post-traumatic osteoarthritis by alpha 2-macroglobulin-rich serum

Purpose: Altered joint loading by trauma induces joint degeneration, eventually leading to the generation of post-traumaticosteoarthritis (PTOA). Recent studies have shown that alpha 2-macroglobulin (A2M)inhibits PTOA, induced by anterior cruciate ligament transection (ACLT),pathogenesis by regulating proinflammatory cytokines and matrixmetalloproteinases. However, the application of A2M is limited due to highprices. Therefore, the aim of this study is to explore the novel preparation of A2M. Materials and Methods: The early change of A2M in synovial fluid and serum was measured by ELISA.Ultra-filtered centrifugation was performed to prepare alpha 2-macroglobulin-richserum (A2MRS). The bioactivity of A2M in A2MRS was detected by improved Ellisand Gollas-Galvan method. The effects of A2MRS on PTOA were observed using immunohistochemistry,safranine O staining, micro X-ray, fluorescence molecular tomography etc. Results: The concentration of A2M in PTOA group wassignificantly higher than that in Sham group in synovial fluid on the third dayafter ACLT in rat PTOA model. On the contrary, a significant downregulation ofA2M levels in PTOA group was observed compared to the Sham group in serum at the seventh day after ACLT. Secondly, A2MRS was prepared successfully, and the concentration and bioactivity of A2M in A2MRS was significantly higher than that in serum. Lastly, A2MRS not only reduced notably the production of secondary cartilage ossification, type 10 collagen and matrix metalloproteinase13, but also increased profoundly the generation of type 2 collagen, aggrecan,and chondrocytes' number. Conclusion: Our results indicate that A2MRS has protective effects on PTOA.