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IL-10 induces MC3T3-E1 cells differentiation towards osteoblastic fate in murine model.

ABSTRACT: Interleukin-10 (IL-10) displays well-documented anti-inflammatory effects, but its effects on osteoblast differentiation have not been investigated. In this study, we found IL-10 negatively regulates microRNA-7025-5p (miR-7025-5p), the down-regulation of which enhances osteoblast differentiation. Furthermore, through luciferase reporter assays, we found evidence that insulin-like growth factor 1 receptor (IGF1R) is a miR-7025-5p target gene that positively regulates osteoblast differentiation. In vivo studies indicated that the pre-injection of IL-10 leads to increased bone formation, while agomiR-7025-5p injection delays fracture healing. Taken together, these results indicate that IL-10 induces osteoblast differentiation via regulation of the miR-7025-5p/IGF1R axis. IL-10 therefore represents a promising therapeutic strategy to promote fracture healing.

SUBMITTER: Xiong Y

PROVIDER: S-EPMC6933380 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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IL-10 induces MC3T3-E1 cells differentiation towards osteoblastic fate in murine model.

Xiong Yuan Y Yan Chenchen C Chen Lang L Endo Yori Y Sun Yun Y Zhou Wu W Hu Yiqiang Y Hu Liangcong L Chen Dong D Xue Hang H Mi Bobin B Liu Guohui G

Journal of cellular and molecular medicine 20191121 1

Interleukin-10 (IL-10) displays well-documented anti-inflammatory effects, but its effects on osteoblast differentiation have not been investigated. In this study, we found IL-10 negatively regulates microRNA-7025-5p (miR-7025-5p), the down-regulation of which enhances osteoblast differentiation. Furthermore, through luciferase reporter assays, we found evidence that insulin-like growth factor 1 receptor (IGF1R) is a miR-7025-5p target gene that positively regulates osteoblast differentiation. I ...[more]

PMID: 31755174

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Project description:BackgroundIn mouse, it was discovered that resveratrol (Res) enhanced osteoporosis (OP) by boosting osteogenesis. Besides, Res can also have an impact on MC3T3-E1 cells, which are crucial for the control of osteogenesis and thus increase osteogenesis. Although some articles have discovered that Res enhanced autophagy to promote the value-added differentiation of MC3T3, it is unclear exactly how this affects the process of osteogenesis in mouse. Therefore, we will show that Res encourages MC3T3-E1 proliferation and differentiation in mouse pre-osteoblasts and further investigate the autophagy-related mechanism for this impact.Methods(1) MC3T3-E1 cells were separated into blank control group and various concentrations (0.01, 0.1, 1, 10, 100µmol/L) of group in order to determine the ideal Res concentration. In the Res group, Cell Counting Kit-8 (CCK-8) was used to measure the proliferation activity of pre-osteoblasts in mice in each group after resveratrol intervention. Alkaline Phosphatase (ALP) and alizarin red staining were used to gauge the degree of osteogenic differentiation, and RT-qPCR was used to measure the expression levels of Runx2 and OCN in the osteogenic differentiation ability of the cells. (2) In the experiment, four groups were set up: the control group, 3MA group, Res group, and Res + 3MA group. To examine cell mineralization, ALP and alizarin red staining were utilized. RT-qPCR and Western blot detection of cell autophagy activity levels and osteogenic differentiation capacity in each group following intervention.Results(1) Resveratrol might increase the number of mice pre-osteoblast, with the impact being most pronounced at 10µmol/L (P < 0.05). The nodules developed substantially more often than in the blank control group, and Runx2 and OCN expressions significantly increased (P < 0.05). (2) In contrast to the Res group, after 3MA purine blocked autophagy, the Res + 3MA group's alkaline phosphatase staining and the development of mineralized nodules were reduced. Runx2, OCN, LC3II / LC3I expression decreased, p62 expression increased (P < 0.05).ConclusionThe present study partially or indirectly demonstrated that Res may, through increased autophagy, induce osteogenic differentiation of MC3T3-E1 cells.

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IL-10 induces MC3T3-E1 cells differentiation towards osteoblastic fate in murine model.

Publications

IL-10 induces MC3T3-E1 cells differentiation towards osteoblastic fate in murine model.

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