Extracellular IL-37 promotes osteogenic differentiation of human bone marrow mesenchymal stem cells via activation of the PI3K/AKT signaling pathway.

Content Provider	Europe PMC
Author	Ye, Chenyi Zhang, Wei Hang, Kai Chen, Mo Hou, Weiduo Chen, Jianzhong Chen, Xi Chen, Erman Tang, Lan Lu, Jinwei Ding, Qianhai Jiang, Guangyao Hong, Baojian He, Rongxin
Abstract	Interleukin (IL)-37, a pivotal anti-inflammatory cytokine and a fundamental inhibitor of innate immunity, has recently been shown to be abnormally expressed in several autoimmune-related orthopedic diseases, including rheumatoid arthritis, ankylosing spondylitis, and osteoporosis. However, the role of IL-37 during osteogenic differentiation of mesenchymal stem cells (MSCs) remains largely unknown. In this study, extracellular IL-37 significantly increased osteoblast-specific gene expression, the number of mineral deposits, and alkaline phosphatase activity of MSCs. Moreover, a signaling pathway was activated in the presence of IL-37. The enhanced osteogenic differentiation of MSCs due to supplementation of IL-37 was partially rescued by the presence of a PI3K/AKT signaling inhibitor. Using a rat calvarial bone defect model, IL-37 significantly improved bone healing. Collectively, these findings indicate that extracellular IL-37 enhanced osteogenesis of MSCs, at least in part by activation of the PI3K/AKT signaling pathway.
Journal	Cell Death & Disease
Volume Number	10
PubMed Central reference number	PMC6776644
Issue Number	10
PubMed reference number	31582734
e-ISSN	20414889
DOI	10.1038/s41419-019-1904-7
Language	English
Publisher	Nature Publishing Group
Publisher Date	2019-10-03
Publisher Place	London
Access Restriction	Open
Rights License	Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2019
Subject Keyword	Differentiation Mesenchymal stem cells
Content Type	Text
Resource Type	Article
Subject	Cell Biology Immunology Cellular and Molecular Neuroscience Medicine Cancer Research