Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107# Yan Jiang Road West, Guangzhou, Guangdong, 510120, People's Republic of China.
Center for Biotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107# Yan Jiang Road West, Guangzhou, Guangdong, 510120, People's Republic of China.
Stem Cell Res Ther. 2018 Jan 22;9(1):13. doi: 10.1186/s13287-017-0766-0.
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.
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.
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.
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.
白细胞介素-6（IL-6）及其受体（IL-6R）在体内组织再生中发挥重要作用，特别是骨代谢。骨髓间充质干细胞（BM-MSCs）是多能基质细胞，是成骨细胞的主要来源。然而，IL-6 和 IL-6R 在 BM-MSCs 成骨分化中的作用尚不清楚。
检测 BM-MSCs 成骨分化过程中 IL-6 和 IL-6R 的表达。评估 STAT3 通路的激活及其在 BM-MSCs 成骨分化中的作用，使用特异性抑制剂 AG490。使用外源性 IL-6/可溶性 IL-6R 或抗 IL-6/IL-6R 抗体来验证 IL-6/IL-6R 复合物促进成骨分化的机制。
在 BM-MSCs 的成骨分化过程中，IL-6 和 IL-6R 的水平，特别是膜结合型 IL-6R 的水平，而不是可溶性 IL-6R 的水平，增加。IL-6 和 IL-6R 的水平与 BM-MSCs 的成骨潜能呈正相关。STAT3 信号通路在 BM-MSCs 的成骨分化过程中被激活。AG490 显著抑制 STAT3 通路的激活，进而抑制 BM-MSCs 的成骨分化潜能。此外，外源性 IL-6 和可溶性 IL-6R 加速了 BM-MSCs 的成骨分化。相反，抗 IL-6 或 IL-6R 的抗体抑制了 BM-MSCs 的成骨分化。此外，在 BM-MSCs 中发现 IL-6 和 IL-6R 相互刺激彼此的表达。
IL-6 和 IL-6R 的水平在 BM-MSCs 的成骨分化过程中增加。这两种分子形成复合物激活下游 STAT3 信号通路，通过自分泌/旁分泌反馈环促进 BM-MSCs 的成骨分化。
