Title：Myeloperoxidase controls bone turnover by suppressing osteoclast differentiation through modulating reactive oxygen species level

Author：Zhao X, Lin S, Li H, Si S and Wang Z

Journal：J Bone Mineral Res

IF：5.854

Year：2021

Volume/Issue/Page：36(3):591-603

Myeloperoxidase (MPO) is a heme peroxidase that plays an important role in innate immunity for host defense against invading microorganisms by catalyzing hydrogen peroxide (H2 O2 )-mediated reactions. Although many reports indicate MPO exerts beneficial or detrimental effects on a variety of inflammatory diseases, little is known with regard to its functional role in bone homeostasis in vivo. Here, our work demonstrates that MPO was transcriptionally downregulated in response to osteoclastogenic stimuli and that exogenous alteration of MPO expression negatively regulated osteoclast (OC) differentiation in vitro. Genetic ablation of Mpo resulted in osteoporotic phenotypes and potentiated bone-resorptive capacity in mice. Mechanistically, accumulation of intracellular H2 O2 and reactive oxygen species (ROS) were observed in MPO deficiency, and MPO overexpression suppressed ROS production in mouse OC precursors. Moreover, a ROS scavenger Tempol inhibited the effect of MPO deficiency on OC formation and function as well as on receptor activator of nuclear factor-κB ligand (RANKL)-initiated transduction signal activation including NF-κB, mitogen-activated protein kinases (MAPKs), and Akt, indicating the increased ROS caused by MPO deficiency contributes to osteoclastogenesis. Taken together, our data demonstrate that MPO has a protective role in bone turnover by limiting osteoclastogenesis and bone resorption physiologically through modulating intracellular H2 O2 level. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).