Wnt7b-induced Sox11 functions enhance self-renewal and osteogenic commitment of bone marrow mesenchymal stem cells
| Autor: | Xueyang Liao, Fanzi Wu, Chenglin Wang, Ling Ye, Yu Shi, Xin Li, Feifei Li, Yitian Wang, Fanyuan Yu |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Population Bone Marrow Cells Bone healing Biology SOXC Transcription Factors Mice 03 medical and health sciences 0302 clinical medicine stomatognathic system SOX2 Osteogenesis Proto-Oncogene Proteins medicine Animals Humans education Mice Inbred BALB C education.field_of_study Mesenchymal stem cell Wnt signaling pathway Mesenchymal Stem Cells Osteoblast Cell Biology Cell biology Mice Inbred C57BL Wnt Proteins RUNX2 Transplantation Disease Models Animal 030104 developmental biology medicine.anatomical_structure Molecular Medicine sense organs 030217 neurology & neurosurgery Signal Transduction Developmental Biology |
| Zdroj: | Stem Cells. 38:1020-1033 |
| ISSN: | 1549-4918 1066-5099 |
| DOI: | 10.1002/stem.3192 |
| Popis: | As a profoundly anabolic regulator of bone, Wnt7b is well acknowledged to enhance osteoblast activities. Here, we report that bone marrow mesenchymal stem cells (BMSCs) are another important population responding to Wnt7b. In this study, we systematically investigated the in vivo role of Wnt7b in BMSCs using transgenic mice, high-throughput RNA-seq, immunohistochemistry, RT-qPCR, and in situ hybridization. These methods led us to uncover that Sox11 is induced via Wnt7b in BMSCs. Colony formation assay, flow cytometry, EdU incorporation labeling, RT-qPCR, and Western blot were conducted to detect the self-renewal capacity of BMSCs. Alkaline phosphatase staining, alizarin red staining, and ex vivo BMSCs transplantation were utilized to detect the osteogenic ability of BMSCs. ChIP-qPCR, shRNAs, and immunofluorescence staining were utilized to investigate the underlying mechanisms. Consequently, bone-derived Wnt7b was found to decrease in osteoporosis and elevate in bone fracture healing. During bone fracture healing, Wnt7b was particularly expressed in the mesenchymal cells residing within healing frontiers. RNA-seq data of Wnt7b-overexpressed bones uncovered the significant upregulation of Sox11. Histological results further unveiled that Sox11 is specifically increased in BMSCs. Wnt7b-induced Sox11 was demonstrated to reinforce both self-renewal and osteogenic differentiation of BMSCs. Mechanistically, Wnt7b activates the Ca2+-dependent Nfatc1 signaling to directly induce Sox11 transcription, which in turn activates the transcriptions of both proliferation-related transcription factors (Ccnb1 and Sox2) and osteogenesis-related factors (Runx2, Sp7) in BMSCs. It is intriguing that this Wnt7b-Sox11 signaling in BMSCs is β-Catenin-independent. Overall, this study provides brand new insights of Wnt7b in bone formation, namely, Wnt7b can enhance both self-renewal and osteogenic differentiation of BMSCs via inducing Sox11. These findings present a new crosstalk between Wnt and Sox signaling in BMSCs. |
| Databáze: | OpenAIRE |
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