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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkaline Phosphatase / metabolism
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Animals
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Calcium / metabolism
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Cell Death / genetics
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Cell Differentiation* / genetics
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Cell Proliferation / genetics
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Collagen Type I / genetics
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Collagen Type I / metabolism
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Collagen Type I, alpha 1 Chain
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Core Binding Factor Alpha 1 Subunit / genetics
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Core Binding Factor Alpha 1 Subunit / metabolism
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Disease Models, Animal
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Extracellular Space / metabolism*
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Gene Expression Regulation
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Humans
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Imaging, Three-Dimensional
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Interleukin-1 / metabolism*
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Male
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Mesenchymal Stem Cells / cytology*
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Mesenchymal Stem Cells / metabolism*
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Osteocalcin / genetics
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Osteocalcin / metabolism
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Osteogenesis* / genetics
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Phosphatidylinositol 3-Kinases / metabolism*
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Proto-Oncogene Proteins c-akt / metabolism*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Rats, Sprague-Dawley
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Signal Transduction
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Skull / diagnostic imaging
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Skull / pathology
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Wound Healing
Substances
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Collagen Type I
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Collagen Type I, alpha 1 Chain
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Core Binding Factor Alpha 1 Subunit
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IL37 protein, human
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Interleukin-1
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RNA, Messenger
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Osteocalcin
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Proto-Oncogene Proteins c-akt
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Alkaline Phosphatase
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Calcium