Liu Shuang, Zhang Enjiao, Yang Mingliang, Lu Li
Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, 117 North Nanjing Street, 110001, Shenyang, People's Republic of China.
Mol Cell Biochem. 2014 May;390(1-2):123-31. doi: 10.1007/s11010-014-1963-0. Epub 2014 Jan 29.
Bone marrow-derived mesenchymal stem cells (MSCs), the most widely used cell source for cartilage tissue engineering, are multipotent cells which have been shown to differentiate into various mesenchyme-lineage cell types including chondrocytes. However, the molecular mechanisms controlling the chondrogenic differentiation of MSCs remain to be fully elucidated. It has been demonstrated that Wnt signaling involves regulating chondrogenesis and MSC differentiation. The aim of the present study was to investigate the role of Wnt11, a member of noncanonical Wnts, in MSCs during chondrogenic differentiation. We observed that overexpression of Wnt11 inhibited proliferation of MSCs and caused a G0/G1 cell cycle arrest. The expression level of chondrogenic markers, aggrecan and Collagen II, was significantly increased in MSCs transduced with Wnt11 as compared with non-transduced cells or MSCs transduced with the empty lentiviral vector. Furthermore, ectopic expression of Wnt11 stimulated gene expression of chondrogenic regulators, SRY-related gene 9, Runt-related transcription factor 2, and Indian hedgehog. Finally, Wnt11 overexpression promoted chondrogenic differentiation of MSCs in synergism with TGF-β. Collectively, these results indicate that Wnt11 plays a crucial role in regulating MSC chondrogenic differentiation.
骨髓间充质干细胞（MSCs）是软骨组织工程中使用最广泛的细胞来源，是一种多能细胞，已被证明可分化为包括软骨细胞在内的各种间充质谱系细胞类型。然而，控制MSCs软骨分化的分子机制仍有待充分阐明。已经证明，Wnt信号传导参与调节软骨生成和MSC分化。本研究的目的是探讨非经典Wnts成员Wnt11在MSCs软骨分化过程中的作用。我们观察到，Wnt11的过表达抑制了MSCs的增殖并导致G0/G1细胞周期停滞。与未转导的细胞或用空慢病毒载体转导的MSCs相比，用Wnt11转导的MSCs中软骨生成标志物聚集蛋白聚糖和胶原蛋白II的表达水平显著增加。此外，Wnt11的异位表达刺激了软骨生成调节因子、SRY相关基因9、Runt相关转录因子2和印度刺猬的基因表达。最后，Wnt11过表达与TGF-β协同促进MSCs的软骨分化。总之，这些结果表明Wnt11在调节MSCs软骨分化中起关键作用。
