Wnt7a Promotes Osteogenic Differentiation of Human Mesenchymal Stem Cells

Background: Mesenchymal stem cells (MSCs) have the ability of differentiating into bone. Elucidating the molecular mechanisms of MSC differentiation into bone could provide new therapeutic strategy for bone-related diseases. Growing evidence confirmed that Wnt signal played the key role in osteoblast differentiation, but the role of individual Wnt protein in osteogenesis need to be investigated. Here, we aim to explore the role of Wnt7a in bone formation. Methods: Human bone-derived MSCs were identified by flow cytometry and its differentiation potentials. Wnt7a expression were measured by osteogenic inducer BMP4/7 treatmemt, osteogenenic or adipogenic differentiation. The influence of Wnt7a ectopic expression in MSCs on osteogenic differentiation were detected by osteocyte markers and Alizarin Red S staining. The mechanismof Wnt7a regulating Runx2 expression were detected by promoter reporter assay and ChIP assay. Findings: Our results showed that knockdown of Wnt7a in MSCs decreased the expression of osteocyte markers and inhibited osteogenic differentiation. Concordantly, the overexpression of Wnt7a in MSCs increased the expression of osteocyte marker and promoted osteogenic differentiation. Mechanistically, the knockdown of Wnt7a in MSCs reduced Runx2 expression and the overexpression of Wnt7a in MSCs promoted Runx2 expression. Furtherly, we confirm that Wnt7a regulated Runx2 promoter activities by promoter report assay, and TCF1, a downstream target of Wnt, binding to the Runx2 promoter by ChIP assay. Interpretation: Our research confirmed that Wnt7a played a key role in MSCs differentiation into bone and this maybe provide a promising therapy target for bone-related disease. Funding Statement: This work was supported with funding from the National Natural Science Foundation of China (No. 81860516), the start-up grant from the Affiliated Hospital of Guizhou Medical University (No. I201802), Guizhou science and Technology Department (No. 2016J7234), Guizhou science and Technology Department (No. 2014LH7149), the National Natural Science Foundation of China (No.81460448), the R&D infrastructure and facility Development and Program of Guizhou (No. 20154005). Declaration of Interests: The authors declare no competing financial interests. Ethics Approval Statement: Human bone tissues from surgical resection were from patients in the Department of Orthopedics of the Affiliated Hospital of Guiyang Medical University. All work and protocols were under the guidelines by the Human Care and Use Committee of Guiyang Medical University. Each patient wrote informed consent before the preparation of the bone tissues.