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Publication : Myokine Irisin promotes osteogenesis by activating BMP/SMAD signaling via αV integrin and regulates bone mass in mice.

First Author  Xue Y Year  2022
Journal  Int J Biol Sci Volume  18
Issue  2 Pages  572-584
PubMed ID  35002510 Mgi Jnum  J:322254
Mgi Id  MGI:6853462 Doi  10.7150/ijbs.63505
Citation  Xue Y, et al. (2022) Myokine Irisin promotes osteogenesis by activating BMP/SMAD signaling via alphaV integrin and regulates bone mass in mice. Int J Biol Sci 18(2):572-584
abstractText  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 alphaV 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 alphaV integrin and activating BMP/SMAD signaling consequently. Thus, irisin may be a promising therapeutic target for osteoporosis and bone defects.
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