Molecular determinants for the polarization of macrophage and osteoclast

  • Dengbao Yang
  • Yihong WanEmail author


Emerging evidence suggest that macrophage and osteoclast are two competing differentiation outcomes from myeloid progenitors. In this review, we summarize recent advances in the understanding of the molecular mechanisms controlling the polarization of macrophage and osteoclast. These include nuclear receptors/transcription factors such as peroxisome proliferator-activated receptor γ (PPARγ) and estrogen-related receptor α (ERRα), their transcription cofactor PPARγ coactivator 1-β (PGC-1β), metabolic factors such as mitochondrial complex I (CI) component NADH:ubiquinone oxidoreductase iron-sulfur protein 4 (Ndufs4), as well as transmembrane receptors such as very-low-density-lipoprotein receptor (VLDLR). These molecular rheostats promote osteoclast differentiation but suppress proinflammatory macrophage activation and inflammation, by acting lineage-intrinsically, systemically or cross generation. These findings provide new insights to the understanding of the interactions between innate immunity and bone remodeling, advancing the field of osteoimmunology.


Bone Osteoimmunology Macrophage Osteoclast PPARγ ERRα PGC-1β Ndufs4 VLDLR 



Y.W. is Lawrence Raisz Professor in Bone Cell Metabolism and a Virginia Murchison Linthicum Scholar in Medical Research.

Funding information

This work was in part supported by NIH (R01CA229487, R01CA236802, Y.W.), DOD (W81XWH-18-1-0014, Y.W.), CPRIT (RP180047, Y.W.), The Welch Foundation (I-1751, Y.W.), and UT Southwestern Endowed Scholar Startup Fund (Y.W.).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of PharmacologyThe University of Texas Southwestern Medical CenterDallasUSA

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