Irisin Enhances Mitochondrial Function in Osteoclast Progenitors during Differentiation

Abstract

Irisin is a myokine released from muscle during exercise with distinct signaling effects on tissues throughout the body, including an influence on skeletal remodeling. Our previous work has shown that irisin stimulates resorption, a key first step in bone remodeling, by enhancing osteoclastogenesis. The present study further investigates the action of irisin on the metabolic function of osteoclast progenitors during differentiation. Fluorescent imaging showed increased mitochondrial content and reactive oxygen species production with irisin treatment in osteoclast progenitors after 48 h of osteoclastogenic culture. Mitochondrial stress testing demonstrated a significant increase in maximal oxygen consumption rate and spare capacity after 48 h of preconditioning with irisin treatment. Together, these findings further elucidate the stimulatory action of irisin on osteoclastogenesis, demonstrating an enhancement of metabolism through mitochondrial respiration in the progenitor to support the energy demands of their differentiation into mature osteoclasts.