富α2巨球蛋白血清改善创伤后骨关节炎症状。

IF 2.8 4区 医学 Q3 CELL BIOLOGY Connective Tissue Research Pub Date : 2022-11-01 Epub Date: 2022-03-19 DOI:10.1080/03008207.2022.2051499
Xiaohu Wang, Lu Li, Xiaochun Wei, Pengcui Li, Yu Zhao, Ruipeng Zhao, Zhiqing Duan
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引用次数: 1

摘要

目的:创伤改变关节负荷可导致关节退变,最终导致创伤后骨关节炎(PTOA)的产生。近期研究表明,α2-巨球蛋白(A2M)通过调节促炎因子和基质金属蛋白酶抑制前交叉韧带横断(ACLT)所致的pta的发病机制。然而,由于价格高,A2M的应用受到限制。因此,本研究的目的是探索A2M的新型制备方法。材料与方法:采用ELISA法测定血清及滑液中A2M的早期变化。超滤离心制备富α2巨球蛋白血清(A2MRS)。采用改良Ellis和Gollas-Galvan法检测A2M在A2MRS中的生物活性。采用免疫组化、红素O染色、微x线、荧光分子层析等方法观察A2MRS对大鼠PTOA模型的影响。结果:ACLT后第3天,PTOA组滑膜液中A2MRS浓度明显高于Sham组。相反,与Sham组相比,toa组在ACLT后第7天血清中A2M水平明显下调。其次,A2MRS制备成功,A2MRS中A2M的浓度和生物活性显著高于血清。最后,A2MRS不仅显著减少了软骨继发性骨化、10型胶原蛋白和基质金属蛋白酶13的生成,而且显著增加了2型胶原蛋白、聚集蛋白的生成和软骨细胞的数量。结论:A2MRS对pta有保护作用。
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Improving the symptoms of post-traumatic osteoarthritis by α2-macroglobulin-rich serum.

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.

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来源期刊
Connective Tissue Research
Connective Tissue Research 生物-细胞生物学
CiteScore
6.60
自引率
3.40%
发文量
37
审稿时长
2 months
期刊介绍: The aim of Connective Tissue Research is to present original and significant research in all basic areas of connective tissue and matrix biology. The journal also provides topical reviews and, on occasion, the proceedings of conferences in areas of special interest at which original work is presented. The journal supports an interdisciplinary approach; we present a variety of perspectives from different disciplines, including Biochemistry Cell and Molecular Biology Immunology Structural Biology Biophysics Biomechanics Regenerative Medicine The interests of the Editorial Board are to understand, mechanistically, the structure-function relationships in connective tissue extracellular matrix, and its associated cells, through interpretation of sophisticated experimentation using state-of-the-art technologies that include molecular genetics, imaging, immunology, biomechanics and tissue engineering.
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