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通过富含α2-巨球蛋白的血清改善创伤后骨关节炎的症状。

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

机构信息

Orthopedics department, The second hospital of Shanxi Medical University, Taiyuan, Shanxi, China.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, China.

出版信息

Connect Tissue Res. 2022 Nov;63(6):615-624. doi: 10.1080/03008207.2022.2051499. Epub 2022 Mar 19.

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.

摘要

目的

创伤引起的关节负荷改变会导致关节退化,最终导致创伤后骨关节炎(PTOA)的发生。最近的研究表明,α2-巨球蛋白(A2M)通过调节促炎细胞因子和基质金属蛋白酶来抑制前交叉韧带切断(ACLT)诱导的 PTOA 发病机制。然而,由于价格高昂,A2M 的应用受到限制。因此,本研究旨在探索 A2M 的新制剂。

材料和方法

通过 ELISA 测量关节滑液和血清中 A2M 的早期变化。通过超滤离心制备富含α2-巨球蛋白的血清(A2MRS)。通过改良的 Ellis 和 Gollas-Galvan 法检测 A2MRS 中的 A2M 生物活性。通过免疫组织化学、番红 O 染色、微 X 射线、荧光分子断层扫描等方法观察 A2MRS 对 PTOA 的影响。

结果

在大鼠 PTOA 模型 ACLT 后第 3 天,PTOA 组关节滑液中 A2M 的浓度明显高于 Sham 组,而 ACLT 后第 7 天,PTOA 组血清中 A2M 的水平明显低于 Sham 组。其次,成功制备了 A2MRS,A2MRS 中的 A2M 浓度和生物活性明显高于血清。最后,A2MRS 不仅显著减少了次级软骨骨化、型胶原和基质金属蛋白酶 13 的产生,而且显著增加了型胶原、聚集蛋白聚糖和软骨细胞数量的生成。

结论

我们的结果表明,A2MRS 对 PTOA 具有保护作用。

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