IGFBP7 regulates the osteogenic differentiation of bone marrow‐derived mesenchymal stem cellsviaWnt/β‐catenin signaling pathway

Abstract

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.

Reprogramming of human fibroblasts into osteoblasts by insulin-like growth factor-binding protein 7

“…Using a proteomics approach we identified a number of candidate factors that are differentially expressed in the secretome of osteoblasts compared to that of fibroblasts. Among them, IGFBP7 is the most promising candidate based on recent reports on its involvement in bone diseases and osteogenic differentiation in mesenchymal stem cells . Our in vitro and in vivo studies support IGFBP7 as potent protein for osteoblastic reprogramming of fibroblasts.…”

“…Among the 17 upregulated proteins in Cluster B, IBP7 (or IGFBP7) showed a 46‐fold increase in abundance in OB‐CM compared to FB‐CM. IGFBP7 has recently been implicated in directing mesenchymal stem cells toward an osteogenic lineage . It has also been associated with induction of cellular senescence, which is increasingly appreciated as having a role in cellular reprogramming and tissue repair .…”

“…It is possible that activation of other signaling pathways by IGFBP7 also contributes to osteogenic phenotype in fibroblasts. For instance, it has been shown that IGFBP7 can activate Wnt signaling that is important for upregulation of osteogenic gene expression and bone repair …”

IGFBP7 acts as a negative regulator of RANKL‐induced osteoclastogenesis and oestrogen deficiency‐induced bone loss

“…Using protein interaction and microRNA network analyses, Wang et al reported that IGFBP7 expression was associated with the development of osteoarthritis (OA), which was confirmed by two other studies . In our previous study, we reported that IGFBP7 enhanced osteogenic differentiation of BMSCs via the Wnt/β‐catenin signalling pathway in vitro and promoted new bone formation in vivo . However, the function of IGFBP7 in osteoclast differentiation and osteoporosis still remains unclear.…”

“…To investigate the effect of IGFBP7 on mineralization, alizarin red staining (ARS) was applied at 14 days after the induction of osteogenic differentiation, using 1% solution of ARS kit (Cyagen Biosciences). The steps of ALP staining and ARS, together with the quantification, were consistent with our previous studies, strictly following the manufacturers’ instructions.…”