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IGFBP7 regulates the osteogenic differentiation of bone marrow‐derived mesenchymal stem cells via Wnt/β‐catenin signaling pathway
Author(s) -
Zhang Wei,
Chen Erman,
Chen Mo,
Ye Chenyi,
Qi Yiying,
Ding Qianhai,
Li Hang,
Xue Deting,
Gao Xiang,
Pan Zhijun
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201700998rr
Subject(s) - wnt signaling pathway , mesenchymal stem cell , chemistry , microbiology and biotechnology , gene knockdown , catenin , runx2 , stem cell , alkaline phosphatase , signal transduction , biology , biochemistry , gene , enzyme
Insulin‐like growth factor‐binding protein 7 (IGFBP7), a low‐affinity IGF binder, may play an important role in bone metabolism. However, its function in osteogenic differentiation of human bone marrow‐derived mesenchymal stem cells (BMSCs) remains unclear. Therefore, we investigated its effects on osteogenic differentiation. Overexpression of IGFBP7 enhanced the expression of osteo‐specific genes and proteins, and IGFBP7 knockdown decreased osteogenesis‐specific markers. More mineral deposits and higher alkaline phosphatase activity were observed after the up‐regulation of IGFBP7 . Moreover, β‐catenin levels were up‐regulated by the overexpression of IGFBP7 or the addition of extracellular IGFBP7 protein and were reduced by the depletion of IGFBP7 . The increase in osteogenic differentiation due to the overexpression of IGFBP7 was partially decreased by specific Wnt/β‐catenin signaling inhibitors. Using a rat tibial osteotomy model, a sheet of IGFBP7–overexpressing BMSCs improved bone healing, as demonstrated by imaging, biomechanical, and histologic analyses. Taken together, these findings indicate that IGFBP7 regulates the osteogenic differentiation of BMSCs partly via the Wnt/ β‐catenin signaling pathway.— Zhang, W., Chen, E., Chen, M., Ye, C., Qi, Y., Ding, Q., Li, H., Xue, D., Gao, X., Pan, Z. IGFBP7 regulates the osteogenic differentiation of bone marrow‐derived mesenchymal stem cells via Wnt/β‐catenin signaling pathway. FASEB J. 32, 2280–2291 (2018). www.fasebj.org