# Irisin inhibits adipogenic differentiation of bone marrow mesenchymal stem cells through the SIRT1/RANBP2/FTO signaling axis and protects against osteoporosis

## TL;DR

Irisin prevents fat cell formation in bone marrow stem cells, reducing osteoporosis risk through a specific signaling pathway.

## Contribution

The study identifies a novel SIRT1/RANBP2/FTO signaling axis through which irisin inhibits adipogenic differentiation of BMMSCs.

## Key findings

- Irisin inhibits adipogenic differentiation of BMMSCs in vitro and reduces bone loss in ovariectomized mice.
- SIRT1, activated by irisin, deacetylates RANBP2 to suppress FTO and PPARγ expression, inhibiting fat cell formation.
- Clinical data confirms irisin's relevance in osteoporosis and its protective role against bone marrow obesity.

## Abstract

Abnormal bone marrow obesity caused by the conversion of bone marrow mesenchymal stem cells (BMMSCs) from osteoblast to adipocyte differentiation is one of the significant contributors to age and menopause-related osteoporosis (OP) development. Irisin, one of the myokines, has been reported to be involved in skeletal metabolic diseases, providing new insights into the pathogenesis of OP. However, the specific mechanism of irisin in adipogenic differentiation of BMMSCs has not been thoroughly explored. Clinical data from this study confirmed the expression of irisin in OP and its clinical significance. In addition, irisin inhibited adipogenic differentiation of BMMSCs in vitro and reduced bone loss and abnormal bone marrow obesity in ovariectomized (OVX) mice. Mechanistically, SIRT1 was identified as a downstream target of irisin, and activated SIRT1 inhibited the expression of FTO through deacetylating RANBP2, which downregulated the stability and expression of PPARγ. The current study revealed a novel molecular mechanism by which irisin mediated BMMSCs adipogenesis through the SIRT1/RANBP2/FTO signaling axis.