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Metabolic reprogramming in osteoclasts

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Abstract

Osteoclasts are bone-resorbing cells that play an essential role in the remodeling of the bone. Defects in osteoclasts thus result in unbalanced bone remodeling, leading to numerous pathological conditions such as osteoporosis, bone metastasis, and inflammatory bone erosion. Metabolism is any process a cell utilizes to meet its energetic demand for biological functions. Along with signaling pathways and osteoclast-specific gene expression programs, osteoclast differentiation activates metabolic programs. The energy generated from metabolic reprogramming in osteoclasts not only supports the phenotypic changes from mononuclear precursor cells to multinuclear osteoclasts, but also facilitates bone resorption, a major function of terminally differentiated, mature osteoclasts. While oxidative phosphorylation is studied as a major metabolic pathway that fulfills the energy demands of osteoclasts, all metabolic pathways are closely interconnected. Therefore, it remains important to understand the various aspects of osteoclast metabolism, including the roles and effects of glycolysis, glutaminolysis, fatty acid synthesis, and fatty acid oxidation. Targeting the pathways associated with metabolic reprogramming has shown beneficial effects on pathological conditions. As a result, it is clear that a deeper understanding of metabolic regulation in osteoclasts will offer broader translational potential for the treatment of human bone disorders.

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Acknowledgements

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Funding

This work was supported by grants from the N.I.H. (R01AR069562 and R01 AR073156-01), by Weill Cornell CTSC, and by support for the Rosensweig Genomics Center from The Tow Foundation.

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Authors and Affiliations

  1. Arthritis and Tissue Degeneration Program, David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, 535 East 70th Street, New York, NY, 10021, USA

    Kyung-Hyun Park-Min

  2. Department of Medicine, Weill Cornell Medical College, New York, NY, 10065, USA

    Kyung-Hyun Park-Min

  3. BCMB Allied Program, Weill Cornell Graduate School of Medical Sciences, New York, NY, 10021, USA

    Kyung-Hyun Park-Min

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Correspondence to Kyung-Hyun Park-Min.

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

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Park-Min, KH. Metabolic reprogramming in osteoclasts. Semin Immunopathol 41, 565–572 (2019). https://doi.org/10.1007/s00281-019-00757-0

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