Overexpression of Wnt11 promotes chondrogenic differentiation of bone marrow-derived mesenchymal stem cells in synergism with TGF-β
Overexpression of Wnt11 promotes chondrogenic differentiation of bone marrow-derived mesenchymal stem cells in synergism with TGF-β
复制标题
DOI：
10.1007/s11010-014-1963-0
复制
发表时间：
2014-05-01
影响因子：
4.3
通讯作者：
Lu, Li
中科院分区：
文献类型：
--
作者：
Liu, Shuang;Zhang, Enjiao;Lu, Li
骨髓间充质干细胞（MSCs）是软骨组织工程中应用最广泛的细胞来源，具有多向分化潜能，可分化为包括软骨细胞在内的多种间充质细胞。然而，控制骨髓间充质干细胞软骨分化的分子机制仍有待充分阐明。已经证明Wnt信号转导涉及调节软骨形成和MSC分化。本研究的目的是探讨Wnt 11，非经典Wnt的成员，在骨髓间充质干细胞软骨分化过程中的作用。我们观察到Wnt 11的过表达抑制了MSC的增殖，并导致G 0/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MSC相比，用Wnt 11转导的MSC中软骨形成标记物聚集蛋白聚糖和胶原蛋白II的表达水平显著增加。此外，异位表达Wnt 11刺激软骨形成调节因子，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，Wnt 11过表达与TGF-β协同促进MSC的软骨分化。总的来说，这些结果表明，Wnt 11在调节MSC软骨分化中起着至关重要的作用。
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-beta. Collectively, these results indicate that Wnt11 plays a crucial role in regulating MSC chondrogenic differentiation.