Overexpression of Wnt11 promotes chondrogenic differentiation of bone marrow-derived mesenchymal stem cells in synergism with TGF-β.
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.
Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, 117 North Nanjing Street, 110001, Shenyang, People's Republic of China.
Shuang
S
Liu
Enjiao
E
Zhang
Mingliang
M
Yang
Li
L
Lu
D000818:Animals; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000235:genetics*; D020219:Chondrogenesis / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051381:Rats; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D051153:Wnt Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; C502412:Wnt11 protein, rat