Notch信号通路与关节软骨发育及骨关节炎

Notch signaling pathway, articular cartilage development and osteoarthritis

背景:骨性关节炎时往往伴随软骨细胞间信号转导的异常,提示细胞间信号转导在骨性关节炎发生、发展过程中可能发挥重要作用。目的:综合分析Notch信号通路的最新进展,探讨Notch在调控骨髓间充质干细胞软骨相分化机制、调控软骨发育及软骨发生中的作用,分析Notch信号通路失调与骨关节炎的关系。方法:以Notch signaling pathway,osteoarthritis,chondrocytes,chondrogenesis,bone marrow stem cells为检索词,检索Pubmed数据库(1919-03/2009-02);以Notch信号通路,骨关节炎,软骨细胞,骨髓间充质干细胞为检索词,检索CNKI数据库(2004-02/2008-09)。文献检索语种限制为英文和中文。纳入与Notch信号通路有关的研究、Notch信号通路调控骨髓间充质干细胞软骨相分化机制的研究,以及Notch信号通路失调与骨关节炎的研究。排除重复性研究。以关节软骨的发育调控和软骨细胞的增殖胃评价指标。结果与结论:计算机初检得到632篇文献,根据纳入排除标准,对其中30篇文献进行分析。Notch信号通路是一个在进化过程中高度保守的信号通路,它通过Notch受体与配体的结合、Notch受体的酶切活化、可溶性Notch胞内区转移至细胞核并与CSLDNA结合蛋白相互作用,最终调控靶基因的表达,从而在细胞增殖、分化、凋亡及器官发育中发挥重要的调控作用。目前已证实,Notch信号参与并调控关节软骨的发育、软骨细胞增殖、分化,而Notch信号的失调在骨关节炎的发生、发展中扮演着十分重要的角色。提示深入研究Notch信号在骨性关节炎发病机制中的确切作用将有助于骨性关节炎的靶向治疗,从而为骨性关节炎的治疗开辟更加广阔的前景。

BACKGROUND： Osteoarthritis, often accompanied by cartilage abnormal signal transduction, suggesting that intracellular signal transduction may play an important role in osteoarthritis genesis and development. OBJECTIVE： To review recent advances in the research of Notch signaling pathway, and explore the mechanisms of chondrogenic differentiation of bone marrow mesenchymal stem cells and its role in cartilage development and chondrogenesis. To analysis the role of dysregulated Notch signaling in the development of osteoarthritis. METHODS： Pubmed was undertaken to identify the relevant articles published from March 1919 to February 2009 with the key words of ＂Notch signaling pathway, osteoarthritis, chondrocytes, chondrogenesis, bone marrow stem cells＂ in English. Simultaneously, CNKI Database was searched for relevant articles published from February 2004 to September 2008 with the key words of ＂Notch signaling pathway, osteoarthritis, chondrocytes, chondrogenesis, bone marrow stem cells＂ in Chinese. Articles with the Notch signaling pathway-related research, Notch signaling pathway of bone marrow-derived mesenchymal stem cells, differentiation of cartilage relative to the mechanism studies, and the Notch signaling pathway disorders and osteoarthritis research were included. Reproducibility articles were excluded. Development regulation of articular cartilage and cartilage cell proliferation were considered as evaluation indexes. RESULTS AND CONCLUSION： Of 632 articles retrieved, 30 were included in our study according to the inclusive and exclusive criteria. The Notch pathway is a highly conserved signaling mechanism involved in many processes determining cell fate during development and maintenance of homeostasis of mature tissues in the adult organism. Activation of Notch occurs following Notch receptor/ligand engagement upon cell-cell contact, which initiates translocation of the Notch intracellular domain to the nucleus and activation of target genes. It has been demonstrated that the Notch signaling plays an important role in regulating articular cartilage development and chondrocyte proliferation and differentiation. In recent studies abnormality of notch signaling was also found in disease, which suggests that notch signaling is involved in osteoarthritis initiation and development. Further study of the specific mechanism of notch signaling in the initiation and development of osteoarthritis will enable us to develop targeted approaches in the treatment of osteoarthritis, thus bring more strategies in the future treatment of osteoarthritis.