Intervertebral disc degeneration (IDD) is characterized by the loss of nucleus pulposus cells (NPCs) and phenotypic abnormalities. Accumulating evidence suggests that long noncoding RNAs (lncRNAs) are involved in the pathogenesis of IDD. In this study, we aimed to investigate the functional effects of lncRNA MALAT1 on NPCs in IDD and the possible mechanism governing these effects. We validated the decreased expression of MALAT1 in the IDD tissues, which was associated with decreased Collagen II and Aggrecan expression. In vitro, overexpressed MALAT1 could attenuate the effect of IL-1β on NPC proliferation, apoptosis, and Aggrecan degradation. In vivo, MALAT1 overexpression attenuated the severity of disc degeneration in IDD model rats. Our molecular study further demonstrated that MALAT1 could sponge miR-503, modulate the expression of miR-503, and activate downstream MAPK signaling pathways. The effects of MALAT1 on NPCs were partially reversed/aggregated by miR-503 mimics/inhibitor treatment. Our data suggested that the MALAT1-miR-503-MAPK pathway plays a critical role in NPCs, which may be a potential strategy for alleviating IDD.

中文翻译：

---

LncRNA MALAT1通过海绵miR-503在体内和体外对髓核细胞生物学表现出正效应

椎间盘退变（IDD）的特征是髓核细胞（NPC）丢失和表型异常。越来越多的证据表明，长的非编码RNA（lncRNA）参与了IDD的发病机理。在这项研究中，我们旨在调查lncRNA MALAT1对IDD中NPC的功能作用以及控制这些作用的可能机制。我们验证了IDD组织中MALAT1的表达减少，这与胶原II和Aggrecan的表达减少有关。在体外，过表达的MALAT1可以减弱IL-1β对NPC增殖，凋亡和Aggrecan降解的影响。在体内，MALAT1过表达减轻了IDD模型大鼠椎间盘退变的严重性。我们的分子研究进一步证明，MALAT1可以使miR-503海绵化，调节miR-503的表达，并激活下游MAPK信号通路。miR-503模拟物/抑制剂处理可部分逆转/聚集MALAT1对NPC的作用。我们的数据表明，MALAT1-miR-503-MAPK途径在NPC中起关键作用，这可能是缓解IDD的潜在策略。