TNIIIA2, The Peptide of Tenascin-C, as a Candidate for Preventing Articular Cartilage Degeneration

TNIIIA2, The Peptide of Tenascin-C, as a Candidate for Preventing Articular Cartilage Degeneration
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DOI:
10.1177/1947603520912300
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发表时间:
2020-03-23
期刊:
影响因子:
2.8
通讯作者:
Sudo, Akihiro
Sudo, Akihiro
中科院分区:
医学4区
文献类型:
--
作者:
Hattori, Tetsuya;Hasegawa, Masahiro;Sudo, Akihiro

文献摘要

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TNIIIA 2是细胞外基质糖蛋白腱生蛋白-C的肽。我们评估了关节内注射TNIIIA 2是否可以在骨关节炎小鼠模型中预防关节软骨退行性变而不诱导滑膜炎。设计将每毫升10微克的TNIIIA 2注射到小鼠膝关节(第II组)中以评估对滑膜炎的诱导。对照组注射磷酸盐缓冲盐水(I组)。使用注射后2周和4周的滑膜炎评分评价滑膜炎。切断小鼠膝关节韧带,制作骨关节炎模型。横切后,将10 μ g/mL TNIIIA 2注射到膝关节中(组IV)。对照组在横断后接受磷酸盐缓冲盐水注射(组III)。术后2、4、8、12周分别行苏木精-伊红和番红-O染色。还进行了体外研究以确定TNIIIA 2防止软骨变性的机制。分离、培养人软骨细胞,并用TNIIIA 2处理。各种mRNA的表达,包括炎性细胞因子,和软骨的合成代谢和分解代谢因子进行了比较,使用实时聚合酶链反应.ResultsThere组之间没有差异,在研究中的小鼠关节内注射(组I与组II)。在骨关节炎模型中,我们发现IV组在4周和8周时骨关节炎的发展受到抑制。TNIIIA 2上调肿瘤坏死因子-α,基质金属蛋白酶3,碱性成纤维细胞生长因子的表达。结论我们证明,TNIIIA 2可以防止软骨退变,滑膜炎。
ObjectiveTNIIIA2 is a peptide of the extracellular matrix glycoprotein tenascin-C. We evaluated whether intra-articular injection of TNIIIA2 could prevent articular cartilage degeneration without inducing synovitis in an osteoarthritis mice model.DesignTen micrograms per milliliter of TNIIIA2 were injected into the knee joint of mice (group II) to evaluate the induction of synovitis. The control group received an injection of phosphate buffered saline (group I). Synovitis was evaluated using synovitis score 2 and 4 weeks after injection. The ligaments of knee joints of mice were transected to make the osteoarthritis model. After transection, 10 mu g/mL of TNIIIA2 was injected into the knee joint (group IV). The control group received an injection of phosphate buffered saline after transection (group III). Histologic examinations were made using hematoxylin and eosin and safranin-O staining at 2, 4, 8, and 12 weeks postoperatively. An in vitro study was also performed to determine the mechanism by which TNIIIA2 prevents cartilage degeneration. Human chondrocytes were isolated, cultured, and treated with TNIIIA2. The expressions of various mRNAs, including inflammatory cytokines, and anabolic and catabolic factors for cartilage were compared using real-time polymerase chain reaction.ResultsThere were no differences between groups in the study of intra-articular injection of mice (group I vs. group II). In the osteoarthritis model, we found development of osteoarthritis was suppressed in group IV at 4 and 8 weeks. TNIIIA2 upregulated the expressions of tumor necrosis factor-alpha, matrix metalloproteinase 3, and basic fibroblast growth factor.ConclusionWe demonstrated that TNIIIA2 could prevent cartilage degeneration without synovitis.