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Alternative pathways of osteoclastogenesis in inflammatory arthritis

Nature Reviews Rheumatology volume 11, pages 189–194 (2015)Cite this article

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Abstract

Osteoclasts are cells of haematopoietic origin that are uniquely specialized to degrade bone. Under physiological conditions, the osteoclastogenesis pathway depends on macrophage colony-stimulating factor 1 (CSF-1, also known as M-CSF) and receptor activator of nuclear factor κB ligand (RANKL). However, an emerging hypothesis is that alternative pathways of osteoclast generation might be active during inflammatory arthritis. In this Perspectives article, we summarize the physiological pathway of osteoclastogenesis and then focus on experimental findings that support the hypothesis that infiltrating inflammatory cells and the cytokine milieu provide multiple routes to bone destruction. The precise identity of osteoclast precursor(s) is not yet known. We propose that myeloid cell differentiation during inflammation could be an important contributor to the differentiation of osteoclast populations and their associated pathologies. Understanding the dynamics of osteoclast differentiation in inflammatory arthritis is crucial for the development of therapeutic strategies for inflammatory joint disease in children and adults.

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Figure 1: Bone remodelling and physiological osteoclast differentiation.
Figure 2: Activation of macrophages and pathological osteoclast differentiation.

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Acknowledgements

The authors thank T. Nguyen for graphic design. Research reported in this publication was supported in part by NIH grant R01 AR062173 and SHC grant 250862 (I.E.A.) and by funding from the UCSF-Stanford Arthritis Center of Excellence funded by the Great Western Region of the Arthritis Foundation (E.D.M). The authors apologize to colleagues for omissions imposed by space limitations.

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Authors and Affiliations

  1. Division of Rheumatology, Allergy and Clinical Immunology, University of California, Shriners Hospitals for Children Northern California, 2425 Stockton Boulevard, Room 653A, Sacramento, 95817, CA, USA

    Iannis E. Adamopoulos

  2. Division of Pediatric Rheumatology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, 94305, CA, USA

    Elizabeth D. Mellins

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Both authors researched the data for the article, provided substantial contributions to discussions of content, wrote the article and undertook review and/or editing of the manuscript before submission.

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Correspondence to Iannis E. Adamopoulos.

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Adamopoulos, I., Mellins, E. Alternative pathways of osteoclastogenesis in inflammatory arthritis. Nat Rev Rheumatol 11, 189–194 (2015). https://doi.org/10.1038/nrrheum.2014.198

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