Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Yuzhong, Chongqing 400016, China.
Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Aging (Albany NY). 2020 May 22;12(10):9000-9013. doi: 10.18632/aging.103161.
Articular cartilage defects are common in the clinic but difficult to treat. Exploring the chondrogenic molecular mechanisms of mesenchymal stem cells (MSCs) is of great theoretical interest and industrial significance. Bone morphogenetic protein 2 (BMP2) is a key factor that induces cartilage differentiation and can induce stem cell chondrogenic differentiation. However, the oxidative stress in the microenvironment during cartilage injury and degeneration inhibits cartilage regeneration and homeostasis. Silent mating type information regulator 2 homolog-1 (SIRT1) is an important histone deacetylase that regulates proliferation, differentiation, aging, and inflammation processes; moreover, it is an essential factor for chondrogenesis. The specific mechanism of SIRT1 in cartilage differentiation and homeostasis is still unclear. First, we investigated whether SIRT1 could coordinate BMP2-induced chondrogenic differentiation. Second, we investigated the protective effect of SIRT1 on BMP2-induced MSCs under oxidative stress. The results showed that SIRT1 could promote BMP2-induced chondrogenic differentiation of MSCs, and reduce the apoptosis and decomposition of extracellular matrix under oxidative stress. In summary, these results suggested that SIRT1 plays an important coordination role in BMP2-induced chondrogenic differentiation of stem cells and cartilage maintenance under oxidative stress, establishing the experimental basis for exploring the use of SIRT1 in cartilage defect repair.
关节软骨缺损在临床上很常见，但很难治疗。探索间充质干细胞（MSCs）的软骨发生分子机制具有重要的理论意义和工业意义。骨形态发生蛋白 2（BMP2）是诱导软骨分化的关键因子，可诱导干细胞软骨分化。然而，软骨损伤和退变过程中微环境中的氧化应激抑制了软骨再生和内稳态。沉默交配型信息调节因子 2 同源物-1（SIRT1）是一种重要的组蛋白去乙酰化酶，可调节增殖、分化、衰老和炎症过程；此外，它是软骨发生的必需因素。SIRT1 在软骨分化和内稳态中的具体机制尚不清楚。首先，我们研究了 SIRT1 是否可以协调 BMP2 诱导的软骨分化。其次，我们研究了 SIRT1 在氧化应激下对 BMP2 诱导的 MSC 的保护作用。结果表明，SIRT1 可以促进 MSC 中 BMP2 诱导的软骨分化，并减少氧化应激下细胞外基质的凋亡和分解。总之，这些结果表明 SIRT1 在 BMP2 诱导的干细胞软骨分化和氧化应激下的软骨维持中发挥重要的协调作用，为探索 SIRT1 在软骨缺损修复中的应用奠定了实验基础。
