Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong SAR, China.
Int J Mol Sci. 2022 Jun 14;23(12):6612. doi: 10.3390/ijms23126612.
A growing body of evidence in humans and animal models indicates an association between intervertebral disc degeneration (IDD) and increased fibrotic elements in the nucleus pulposus (NP). These include enhanced matrix turnover along with the abnormal deposition of collagens and other fibrous matrices, the emergence of fibrosis effector cells, such as macrophages and active fibroblasts, and the upregulation of the fibroinflammatory factors TGF-β1 and IL-1/-13. Studies have suggested a role for NP cells in fibroblastic differentiation through the TGF-βR1-Smad2/3 pathway, inflammatory activation and mechanosensing machineries. Moreover, NP fibrosis is linked to abnormal MMP activity, consistent with the role of matrix proteases in regulating tissue fibrosis. MMP-2 and MMP-12 are the two main profibrogenic markers of myofibroblastic NP cells. This review revisits studies in the literature relevant to NP fibrosis in an attempt to stratify its biochemical features and the molecular identity of fibroblastic cells in the context of IDD. Given the role of fibrosis in tissue healing and diseases, the perspective may provide new insights into the pathomechanism of IDD and its management.
越来越多的人体和动物模型证据表明，椎间盘退变（IDD）与髓核（NP）中纤维性成分的增加之间存在关联。这些包括基质周转率的提高以及胶原和其他纤维基质的异常沉积、纤维化效应细胞（如巨噬细胞和活性成纤维细胞）的出现，以及纤维炎症因子 TGF-β1 和 IL-1/-13 的上调。研究表明，NP 细胞通过 TGF-βR1-Smad2/3 途径、炎症激活和机械感应机制在成纤维细胞分化中发挥作用。此外，NP 纤维化与异常的 MMP 活性有关，这与基质蛋白酶在调节组织纤维化中的作用一致。MMP-2 和 MMP-12 是肌成纤维 NP 细胞的两个主要致纤维增生标志物。本综述回顾了文献中与 NP 纤维化相关的研究，试图在 IDD 背景下对其生化特征和纤维细胞的分子特征进行分层。鉴于纤维化在组织愈合和疾病中的作用，这一观点可能为 IDD 的发病机制及其治疗提供新的见解。
