Abstract
Irisin, a skeletal-muscle secreted myokine, facilitates muscle-bone crosstalk and skeletal remodeling in part by its action on osteoblasts and osteocytes. In this study, we investigated whether irisin directly regulates osteoclasts. In vitro, irisin (2-10 ng/mL) increased osteoclast differentiation in C57BL/6J mouse bone marrow progenitors; however, this increase was blocked by a neutralizing antibody to integrin αVβ5. Irisin also increased bone resorption on several substrates in situ. RNAseq revealed differential gene expression induced by irisin including upregulation of markers for osteoclast differentiation and resorption, as well as osteoblast-stimulating 'clastokines'. Forced expression of the irisin precursor Fndc5 in transgenic C57BL/6J mice resulted in lower bone mass at three ages and greater in vitro osteoclastogenesis from Fndc5-transgenic bone marrow progenitors. This study demonstrates that irisin acts directly on osteoclast progenitors to increase differentiation and promote bone resorption, supporting the tenet that irisin not only stimulates bone remodeling but may also be an important counter-regulatory hormone.
Highlights
Irisin is a peptide generated by proteolytic cleavage of fibronectin type III domain-containing protein 5 (FNDC5), a membrane-bound protein highly expressed in skeletal muscle
Initial studies demonstrated that irisin enhanced cortical bone formation and prevented unloading-induced bone loss in vivo, and stimulated osteoblasts in vitro[3,4,5]
As integrins are found on the osteoclast membrane and known to play a role in differentiation[7,8], and earlier work identified integrin αVβ5 as a receptor for irisin on osteocytes[6], we examined the expression of both subunits in osteoclast cultures and found increased relative mRNA expression above controls with irisin treatment (Figure 1f)
Summary
Irisin is a peptide generated by proteolytic cleavage of fibronectin type III domain-containing protein 5 (FNDC5), a membrane-bound protein highly expressed in skeletal muscle. Our work demonstrates that irisin acts directly on cultured osteoclast progenitors to increase differentiation and promote bone resorption.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
