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Molecular determinants for the polarization of macrophage and osteoclast

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Abstract

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.

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Acknowledgments

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

Funding

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.).

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  1. Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA

    Dengbao Yang & Yihong Wan

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This article is a contribution to the special issue on Osteoimmunology - Guest Editor: Mary Nakamura

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Yang, D., Wan, Y. Molecular determinants for the polarization of macrophage and osteoclast. Semin Immunopathol 41, 551–563 (2019). https://doi.org/10.1007/s00281-019-00754-3

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