Myokine Irisin promotes osteogenesis by activating BMP/SMAD signaling via αV integrin and regulates bone mass in mice
| Autor: | Xue, Yuan, Hu, Sihan, Chen, Chichi, He, Jiachen, Sun, Jie, Jin, Yesheng, Zhang, Yuanshu, Zhu, Guoqing, Shi, Qin, Rui, Yongjun |
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| Rok vydání: | 2022 |
| Předmět: |
mesenchymal stem/stromal cell
Irisin Bone Morphogenetic Protein 2 Applied Microbiology and Biotechnology αV integrin Collagen Type I Mitochondrial Proteins Mice Osteogenesis Bone Density Animals Molecular Biology Cells Cultured Ecology Evolution Behavior and Systematics Cell Differentiation Mesenchymal Stem Cells BMP/SMAD signaling Cell Biology Integrin alphaV Fibronectins Mice Inbred C57BL Apoptosis Regulatory Proteins Peptides Research Paper Signal Transduction Developmental Biology |
| Zdroj: | International Journal of Biological Sciences |
| ISSN: | 1449-2288 |
| DOI: | 10.7150/ijbs.63505 |
| Popis: | Irisin is well-known to contribute to bone homeostasis due to its bidirectional regulation on osteogenesis and osteoclastogenesis. However, the mechanisms of irisin involved in mesenchymal stem/stromal cells (MSCs)-derived osteogenesis are still under investigated. Fibronectin type III domain-containing protein 5 (FNDC5) is the precursor protein of irisin, compare with wild type (WT) littermates, FNDC5-/- mice lost bone mass significantly, collectively evidenced by the decrease of bone mineral density (BMD), impaired bone formation and reduced N-terminal propertied of type I procollagen (P1NP) in sera. Meanwhile, the bone resorbing of FNDC5-/- mice has enhanced accompanied by increased tartrate phosphatase (TRAP) staining cells morphologically and cross-Linked C-telopeptide of type 1 collagen (CTX) level in sera. In vitro study showed that lack of irisin impeded the MSC-derived osteogenesis of FNDC5-/- mice. The addition of irisin promote the osteogenesis of WT and irisin-deficient MSCs, by activating αV integrin-induced ERK/STAT pathway, subsequently enhancing bone morphogenetic protein 2 (BMP2) expression and BMP/SMAD signaling activation. Taken together, these findings further indicate that irisin regulates bone homeostasis. Moreover, irisin promotes MSC-derived osteogenesis by binding to αV integrin and activating BMP/SMAD signaling consequently. Thus, irisin may be a promising therapeutic target for osteoporosis and bone defects. |
| Databáze: | OpenAIRE |
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