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Mechanisms involved in normal and pathological osteoclastogenesis

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Abstract

Osteoclasts are bone-resorbing cells that play an essential role in bone remodeling. Defects in osteoclasts result in unbalanced bone remodeling and are linked to many bone diseases including osteoporosis, rheumatoid arthritis, primary bone cancer, and skeletal metastases. Receptor activator of NF-kappaB ligand (RANKL) is a classical inducer of osteoclast formation. In the presence of macrophage-colony-stimulating factor, RANKL and co-stimulatory signals synergistically regulate osteoclastogenesis. However, recent discoveries of alternative pathways for RANKL-independent osteoclastogenesis have led to a reassessment of the traditional mechanisms that regulate osteoclast formation. In this review, we provide an overview of signaling pathways and other regulatory elements governing osteoclastogenesis. We also identify how osteoclastogenesis is altered in pathological conditions and discuss therapeutic targets in osteoclasts for the treatment of skeletal diseases.

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Acknowledgements

This work is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award numbers R01 AR069562 and AR073156. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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

    Kyung-Hyun Park-Min

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

    Kyung-Hyun Park-Min

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Park-Min, KH. Mechanisms involved in normal and pathological osteoclastogenesis. Cell. Mol. Life Sci. 75, 2519–2528 (2018). https://doi.org/10.1007/s00018-018-2817-9

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