Expression and regulation of recently discovered hyaluronidases, HYBID and TMEM2, in chondrocytes from knee osteoarthritic cartilage.
Expression and regulation of recently discovered hyaluronidases, HYBID and TMEM2, in chondrocytes from knee osteoarthritic cartilage.
复制标题
DOI：
10.1038/s41598-022-22230-z
复制
发表时间：
2022-10-14
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
骨关节炎 (OA) 中关节软骨的破坏是由透明质酸 (HA)-聚集蛋白聚糖网络的消耗引发的，随后是胶原纤维的降解。之前，我们报道了参与HA解聚的HA结合蛋白（HYBID）（别名细胞迁移诱导蛋白（CEMIP）和KIAA1199）对HA降解的影响。然而，与HYBID同源性≥50%的跨膜蛋白2（TMEM2）被发现是另一种透明质酸酶，但它们的表达和OA软骨细胞的调节仍不清楚。在这里，我们报告 OA 软骨中 HYBID 的绝对 mRNA 拷贝数显着高于正常软骨（7.1 倍），而 TMEM2 水平在各组之间没有差异。通过 siRNA 介导的 HYBID 敲低，培养的 OA 软骨细胞的 HA 降解活性消失，但 TMEM2 却没有。通过白细胞介素-6 (IL-6) 或肿瘤坏死因子-α (TNF-α) 治疗，HYBID 表达显着上调，并通过联合治疗进一步增加。通过检查的因素未发现 TMEM2 表达发生显着变化。当补充可溶性 IL-6 受体时，IL-1α 显着增强 IL-6 的产生并增加 HYBID 的表达。这些结果表明，与 TMEM2 的组成型表达及其可忽略不计的 HA 降解活性形成鲜明对比，HYBID 在 OA 软骨中过度表达，并在 OA 软骨细胞中被 IL-6 和 TNF-α 上调。
Destruction of articular cartilage in osteoarthritis (OA) is initiated by depletion of the hyaluronan (HA)-aggrecan network, followed by degradation of the collagen fibrils. Previously, we reported the implications of HA-binding protein involved in HA depolymerization (HYBID), alias cell migration-inducing protein (CEMIP) and KIAA1199, for HA degradation. However, transmembrane protein 2 (TMEM2), which is ~ 50% homologous to HYBID, was discovered as another hyaluronidase, but their expression and regulation by OA chondrocytes remain elusive. Here we report that the absolute mRNA copy numbers of HYBID are significantly (7.1-fold) higher in OA cartilage than normal cartilage, whereas TMEM2 levels are not different between the groups. HA-degrading activity of cultured OA chondrocytes disappeared by siRNA-mediated knockdown of HYBID, but not TMEM2. HYBID expression was significantly up-regulated by treatment with interleukin-6 (IL-6) or tumor necrosis factor-α (TNF-α) and additively increased by the combined treatment. No significant changes in the TMEM2 expression were seen by the factors examined. IL-1α remarkably enhanced IL-6 production and increased HYBID expression when soluble IL-6 receptor was supplemented. These results demonstrate that in stark contrast to the constitutive expression of TMEM2 and its negligible HA-degrading activity, HYBID is overexpressed in OA cartilage and up-regulated by IL-6 and TNF-α in OA chondrocytes.
登录
查看更多内容
滑膜巨噬细胞和巨噬细胞产生的细胞因子在驱动聚集蛋白聚糖酶、基质金属蛋白酶和骨关节炎中其他破坏性和炎症反应中的作用。
影响因子：
4.9
作者：
Bondeson J;Wainwright SD;Lauder S;Amos N;Hughes CE
通讯作者：
Hughes CE
影响因子：
11.8
作者：
De Angelis, Jessica E.;Lagendijk, Anne K.;Smith, Kelly A.
通讯作者：
Smith, Kelly A.
影响因子：
11.2
作者：
Lee H;Goodarzi H;Tavazoie SF;Alarcón CR
通讯作者：
Alarcón CR
影响因子：
--
作者：
Evensen NA;Li Y;Kuscu C;Liu J;Cathcart J;Banach A;Zhang Q;Li E;Joshi S;Yang J;Denoya PI;Pastorekova S;Zucker S;Shroyer KR;Cao J
通讯作者：
Cao J
影响因子：
7
作者：
Felson, D. T.
通讯作者：
Felson, D. T.