Dataset Information

IL-1? promotes osteogenic differentiation of mouse bone marrow mesenchymal stem cells via the BMP/Smad pathway within a certain concentration range.

ABSTRACT: Inflammatory factors play an important role in the process of fracture healing. The influence of interleukin (IL)-1?, a key inflammatory factory, on new bone formation has been controversial. The aim of the present study was to investigate whether IL-1? affects the osteogenic differentiation of mouse bone marrow mesenchymal stem cells (MBMMSCs), and examined its effective concentration range and molecular mechanism of action. MBMMSC proliferation in the presence of IL-1? was observed using a Cell-Counting Kit-8 assay, and the effect of IL-1? on MBMMSC apoptosis was examined via flow cytometry. Alkaline phosphatase assay, Alizarin Red staining and quantitative assays were performed to evaluate the osteogenic differentiation of MBMMSCs. The expression levels of osteogenic differentiation markers were detected using reverse transcription-quantitative PCR (RT-qPCR). It was demonstrated that within a concentration range of 0.01-1 ng/ml, IL-1? promoted osteogenic differentiation of MBMMSCs and did not induce apoptosis. Furthermore, RT-qPCR results indicated that IL-1? increased osteogenic gene expression within this concentration range. Moreover, Western blotting results identified that the bone morphogenetic protein/Smad (BMP/Smad) signaling pathway was significantly activated by IL-1? under osteogenic conditions. Therefore, the present results suggested that within a certain concentration range, IL-1? promoted osteogenic differentiation and function of MBMMSCs via the BMP/Smad signaling pathway.

SUBMITTER: Wang H

PROVIDER: S-EPMC7444350 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

IL-1β promotes osteogenic differentiation of mouse bone marrow mesenchymal stem cells via the BMP/Smad pathway within a certain concentration range.

Wang Hao H Ni Zhihao Z Yang Jiazhao J Li Meng M Liu Lei L Pan Xuejie X Xu Lei L Wang Xujin X Fang Shiyuan S

Experimental and therapeutic medicine 20200728 4

Inflammatory factors play an important role in the process of fracture healing. The influence of interleukin (IL)-1β, a key inflammatory factory, on new bone formation has been controversial. The aim of the present study was to investigate whether IL-1β affects the osteogenic differentiation of mouse bone marrow mesenchymal stem cells (MBMMSCs), and examined its effective concentration range and molecular mechanism of action. MBMMSC proliferation in the presence of IL-1β was observed using a Cel ...[more]

PMID: 32855666

Similar Datasets

Project description:In patients who were treated with exogenous BMP-2 to repair bone fractures or defects, the levels of the inflammatory cytokines such as TNF-α and IL-1β in sera are significantly elevated, which may affect the outcome of bone regeneration. Mitogen-activated protein kinase (MAPK) cascades such as extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and c-Jun NH2-terminal kinase 1/2 (JNK1/2) have a crucial role in osteogenic differentiation and are activated by both BMP-2 and TNF-α/IL-1β. However, previous studies suggested that the effects of BMP-2 and TNF-α/IL-1β in osteoblastic differentiation are opposite. Here, we investigated the exact role of MAPKs in a BMP-2 and TNF-α/IL-1β co-existed condition. Treatment with TNF-α/IL-1β inhibited BMP-2-induced alkaline phosphatase activity, calcium deposition, osteogenic transcriptional factor Runx2, and the expression of osteogenic markers in C2C12 and MC3T3-E1 cells. This inhibitory effect was independent of the canonical BMP/Smad pathway, suggesting the presence of an alternate regulatory pathway for BMP-2-induced Runx2 activity and subsequent osteoblastic differentiation. We then confirmed that BMP-2, TNF-α, and IL-1β alone can activate p38, ERK1/2, and JNK1/2, respectively. However, only inhibition of p38 and ERK1/2 signaling were required to modulate BMP-2-induced Runx2 expression. Finally, we determined that TNF-α/IL-1β decreased BMP-2-induced Runx2 expression through the activation of p38 and ERK1/2 signaling. Furthermore, strong activation of p38 and ERK1/2 signaling by transfection with CA-MKK3 or CA-MEK1 inhibited BMP-2-induced Runx2 expression and osteoblastic differentiation in C2C12 and MC3T3-E1 cells. Based on these results, we conclude that TNF-α/IL-1β- and BMP-2-activated p38 and ERK1/2 signaling have opposing roles that converge on Runx2 to regulate osteoblastic differentiation. The elucidation of these mechanisms may hasten the development of new strategies and improve the osteoinductive efficacy of BMP-2 in the clinic to enhance osteoblastic differentiation and bone formation.

Dataset Information

IL-1? promotes osteogenic differentiation of mouse bone marrow mesenchymal stem cells via the BMP/Smad pathway within a certain concentration range.

Publications

IL-1β promotes osteogenic differentiation of mouse bone marrow mesenchymal stem cells via the BMP/Smad pathway within a certain concentration range.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets