Journal
STEM CELL RESEARCH & THERAPY
Volume 9, Issue -, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/s13287-017-0766-0
Keywords
Bone marrow-derived mesenchymal stem cells; Osteogenic differentiation; Interleukin-6; Interleukin-6 receptor
Funding
- National Natural Science Foundation of China [81702120]
- Industrial Technology Research and Development Funding Project of Guangdong Province [20160911]
- Clinical Medicine Research and Transformation Project of Guangzhou City [201604020004]
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Background: Interleukin-6 (IL-6) with IL-6 receptor (IL-6R) play an important role in the tissue regeneration in vivo, especially bone metabolism. Bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent stromal cells, which are main origin of osteoblasts. However, the roles of IL-6 and IL-6R in the osteogenic differentiation of BM-MSCs are still unclear. Methods: The expression of IL-6 and IL-6R was detected in BM-MSCs during osteogenic differentiation. The activation of the STAT3 pathway was assessed and its role in the osteogenic differentiation of BM-MSCs was determined using the specific inhibitor AG490. Exogenous IL-6/soluble IL-6R or antibodies against IL-6/IL-6R were used to confirm the mechanism by which the IL-6/IL-6R complex promotes the osteogenic differentiation. Results: The levels of IL-6 and IL-6R, especially the level of membranous IL-6R but not that of soluble IL-6R, increased during osteogenic differentiation in BM-MSCs. The levels of IL-6 and IL-6R were positively correlated with the osteogenic potential of BM-MSCs. The STAT3 signaling pathway was activated during the osteogenic differentiation of BM-MSCs. AG490 markedly inhibited the activation of the STAT3 pathway and, subsequently, the osteogenic differentiation potential of BM-MSCs. Additionally, exogenous IL-6 and soluble IL-6R accelerated the osteogenic differentiation of BM-MSCs. In contrast, antibodies against IL-6 or IL-6R suppressed the osteogenic differentiation of BM-MSCs. Moreover, IL-6 and IL-6R were found to stimulate each other's expression in BM-MSCs. Conclusions: IL-6 and IL-6R levels increase during the osteogenic differentiation of BM-MSCs. These two molecules form a complex to activate the downstream STAT3 signaling pathway, which promotes osteogenic differentiation in BM-MSCs via an autocrine/paracrine feedback loop.
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