Improving the symptoms of post-traumatic osteoarthritis by α2-macroglobulin-rich serum

ABSTRACT

Purpose

Altered joint loading by trauma induces joint degeneration, eventually leading to the generation of post-traumatic osteoarthritis (PTOA). Recent studies have shown that α2-macroglobulin (A2M) inhibits PTOA, induced by anterior cruciate ligament transection (ACLT), pathogenesis by regulating proinflammatory cytokines and matrix metalloproteinases. However, the application of A2M is limited due to high prices. 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 α2-macroglobulin-rich serum (A2MRS). The bioactivity of A2M in A2MRS was detected by improved Ellis and 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 was significantly higher than that in Sham group in synovial fluid on the third day after ACLT in rat PTOA model. On the contrary, a significant downregulation of A2M 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 metalloproteinase 13, 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.

KEYWORDS:

• Α2-macroglobulin
• α2-macroglobulin-rich serum
• post-traumatic osteoarthritis
• articular cartilage degeneration

Acknowledgments

This study was supported by the innovating project of improving medicine by science and technology (Grant No. 2020TD18), the Applied basic research Fund of Shanxi Science and Technology Department (Grant No. 201901D111370), the General project of Shanxi Science and Technology Department (Grant No. 20210302123298), and the Foundation of Shanxi Educational Committee (Grant No. 201802057).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the the Applied Basic Research Fund of Shanxi Science and Technology Department [201901D111370]; the General project of Shanxi Science and Technology Department [20210302123298]; the innovating project of improving medicine by science and technology [2020TD18]; the Foundation of Shanxi Educational Committee [201802057].