Liu Yake, Zhu Hai, Yan Xin, Gu Haoye, Gu Zhifeng, Liu Fan
Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China.
Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China; Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China.
Biochem Biophys Res Commun. 2017 Sep 16;491(2):368-373. doi: 10.1016/j.bbrc.2017.07.094. Epub 2017 Jul 17.
Endoplasmic reticulum stress (ERS) has been shown to participate in many disease pathologies. Recent reports have reported that ERS exists in human osteoarthritis (OA) chondrocytes. During OA, chondrocytes exhibit increased level of some senescence marker, such as senescence-associated β-galactosidase (SA β-gal) activity. However, the persistence and accumulation of senescent cells in various tissues can also impair function and have been involved in the pathogenesis of many age-related diseases, including OA. In this present study, we used IL-1β (10 ng/ml) to mimic OA chondrocytes and we found that IL-1β stimulated chondrocytes caused the increasing expression of ADAMTS5 and MMP13, decreasing COL2A1 expression, which were in accord with OA chondrocytes changes. Our data also showed that ERS is involved in the OA chondrocytes, SA β-gal activity significantly increases and inhibition of ERS can decrease the SA β-gal activity, apoptosis of OA chondrocytes and increase cell viability. These results help us to open new perspectives for the development of molecular-targeted treatment approaches and thus present an effective novel therapeutic approach for OA.
内质网应激（ERS）已被证明参与多种疾病的病理过程。最近的报道称，ERS存在于人类骨关节炎（OA）软骨细胞中。在OA期间，软骨细胞中一些衰老标志物的水平会升高，如衰老相关β-半乳糖苷酶（SA β-gal）活性。然而，衰老细胞在各种组织中的持续存在和积累也会损害功能，并参与包括OA在内的许多与年龄相关疾病的发病机制。在本研究中，我们使用白细胞介素-1β（IL-1β，10 ng/ml）模拟OA软骨细胞，发现IL-1β刺激的软骨细胞会导致ADAMTS5和MMP13表达增加，COL2A1表达减少，这与OA软骨细胞的变化一致。我们的数据还表明，ERS参与OA软骨细胞的过程，SA β-gal活性显著增加，抑制ERS可降低SA β-gal活性、OA软骨细胞凋亡并提高细胞活力。这些结果有助于我们为开发分子靶向治疗方法开辟新的前景，从而为OA提供一种有效的新型治疗方法。
