Marrow adipocytes inhibit the differentiation of mesenchymal stem cells into osteoblasts via suppressing BMP-signaling

Journal of Biomedical Science

Research

Basem M. Abdallah¹ 

[1] Molecular Endocrinology Laboratory (KMEB), Department of Endocrinology, Odense University Hospital and University of Southern Denmark, Odense, Denmark;Department of Biological Sciences, College of Science, King Faisal University, Hofuf, Saudi Arabia;Faculty of Science, Helwan University, Cairo, Egypt;

关键词: Mesenchymal stem cells;    BMSCs;    Osteoblast;    Adipocyte;    Paracrine factors;    osteoblast differentiation;   

DOI  :  10.1186/s12929-017-0321-4

 received in 2016-10-13, accepted in 2017-01-31,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundReduced bone formation is associated with increased bone marrow fat in many bone-loss related diseases including aging, post-menopause, and anorexia nervosa. Several lines of evidence suggested the regulation of osteogenesis and adipogenesis of the bone marrow-derived mesenchymal (skeletal) stem cells (BMSCs) by paracrine mediators. This study aimed to investigate the impact of adipocytes-secreted factors on the cell proliferation and osteoblast differentiation of BMSCs.MethodsSerum free conditioned medium (CM-Adipo) was collected from stromal ST2 cells-derived adipocytes. Cell viability, quantitative alkaline phosphatase (ALP) activity assay, Alizarin red staining for matrix mineralization and osteogenic gene array expression were performed to determine the effect of CM-Adipo on cell proliferation and osteoblast differentiation of primary murine BMSCs (mBMSCs). Regulation of BMPs and NF-κB signaling pathways by CM-Adipo were detected by Western blot analysis and gene reporter assay.ResultsCM-Adipo showed no effect on cell viability/proliferation of primary mBMSCs as compared to CM-control. On the other hand, CM-Adipo significantly inhibited the commitment of mBMSCs into osteoblastic cell lineage in dose-dependent manner. CM-Adipo was found to dramatically inhibit the BMP2-induced osteoblast differentiation and to activate the inflammatory NF-κB signaling in mBMSCs. Interestingly, treatment of mBMSCs with the selective inhibitor of NF-κB pathway, BAY11-770682, showed to retrieve the inhibitory effect of CM-Adipo on BMP2-induced osteoblast differentiation in mBMSCs.ConclusionsOur data demonstrated that the marrow adipocytes exert paracrine inhibitory effect on the osteoblast differentiation of mBMSCs by blocking BMPs signaling in a mechanism mediated by adipokines-induced NF-κB pathway activation.

【 授权许可】

CC BY   
© The Author(s). 2017