HMGB1 promotes the secretion of multiple cytokines and potentiates the osteogenic differentiation of mesenchymal stem cells through the Ras/MAPK signaling pathway.
HMGB1 promotes the secretion of multiple cytokines and potentiates the osteogenic differentiation of mesenchymal stem cells through the Ras/MAPK signaling pathway.
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DOI：
10.3892/etm.2016.3857
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发表时间：
2016-12
影响因子：
2.7
通讯作者：
Pan Z
中科院分区：
文献类型：
--
作者：
Feng L;Xue D;Chen E;Zhang W;Gao X;Yu J;Feng Y;Pan Z
高迁移率族蛋白1（HMGB 1）蛋白先前已在骨折的炎症微环境中检测到。众所周知，HMGB 1作为间充质干细胞（MSC）的化学引诱物。在本研究中，HMGB 1对细胞因子分泌的影响，从骨髓间充质干细胞，并阐明这些影响的HMGB 1的成骨分化的分子机制。为了检测细胞因子分泌，进行抗体阵列测定，其证明HGMB 1诱导细胞因子的差异分泌，所述细胞因子主要与细胞发育、生长和细胞迁移的调节、应激反应和免疫系统功能相关。此外，表皮生长因子受体（EGFR）的分泌显着上调HMGB 1。EGFR激活的Ras/MAPK通路调控MSCs的成骨分化。这些结果表明HMGB 1通过Ras/MAPK信号通路促进MSCs分泌多种细胞因子并促进成骨分化。本研究可为今后骨折治疗新技术的开发提供理论依据。
High mobility group box 1 (HMGB1) protein has been previously been detected in the inflammatory microenvironment of bone fractures. It is well known that HMGB1 acts as a chemoattractant to mesenchymal stem cells (MSCs). In the present study, the effects of HMGB1 on cytokine secretion from MSCs were determined, and the molecular mechanisms underlying these effects of HMGB1 on osteogenic differentiation were elucidated. To detect cytokine secretion, antibody array assays were performed, which demonstrated that HGMB1 induced the differential secretion of cytokines that are predominantly associated with cell development, regulation of growth and cell migration, stress responses, and immune system functions. Moreover, the secretion of epidermal growth factor receptor (EGFR) was significantly upregulated by HMGB1. The EGFR-activated Ras/MAPK pathway regulates the osteogenic differentiation of MSCs. These results suggested that HMGB1 enhances the secretion of various cytokines by MSCs and promotes osteogenic differentiation via the Ras/MAPK signaling pathway. The present study may provide a theoretical basis for the development of novel techniques for the treatment of bone fractures in the future.