Myokine Irisin promotes osteogenesis by activating BMP/SMAD signaling via αV integrin and regulates bone mass in mice |
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Authors: | Yuan Xue Sihan Hu Chichi Chen Jiachen He Jie Sun Yesheng Jin Yuanshu Zhang Guoqing Zhu Qin Shi Yongjun Rui |
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Institution: | 1.Department of Orthopedics, the First Affiliated Hospital of Soochow University, Orthopedics Institute of Soochow University, Medical College of Soochow University, Suzhou, Jiangsu, 215006, P. R. China.;2.Department of Orthopedics, Wuxi Ninth People''s Hospital affiliated to Soochow University, Wuxi, Jiangsu, 214026, P. R. China.;3.Department of Physiology, Nanjing Medical University, 101 Longmian Avenue, Nanjing, Jiangsu, 211166, P. R. China. |
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Abstract: | 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. |
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Keywords: | Irisin mesenchymal stem/stromal cell Osteogenesis BMP/SMAD signaling α V integrin |
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