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Induction of osteoclast progenitors in inflammatory conditions: key to bone destruction in arthritis

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Abstract

The inflammatory milieu favors recruitment and activation of osteoclasts, and leads to bone destruction as a serious complication associated with arthritis and with other inflammatory processes. The frequency and activity of osteoclast progenitors (OCPs) correspond to arthritis severity, and may be used to monitor disease progression and bone resorption, indicating the need for detailed characterization of the discrete OCP subpopulations. Collectively, current studies suggest that the most potent murine bone marrow OCP population can be identified among lymphoid negative population within the immature myeloid lineage cells, as B220−CD3−CD11b–/loCD115+CD117+CX3CR1+ and possibly also Ter119−CD11c−CD135loLy6C+RANK−. In peripheral blood the OCP population bears the monocytoid phenotype B220−CD3−NK1.1−CD11b+Ly6ChiCD115+CX3CR1+, presumably expressing RANK in committed OCPs. Much less is known about human OCPs and their regulation in arthritis, but the circulating OCP subset is, most probably, comprised among the lymphoid negative population (CD3−CD19−CD56−), within immature monocyte subset (CD11b+CD14+CD16−), expressing receptors for M-CSF and RANKL (CD115+RANK+). Our preliminary data confirmed positive association between the proportion of peripheral blood OCPs, defined as CD3−CD19−CD56−CD11b+CD14+, and the disease activity score (DAS28) in the follow-up samples from patients with psoriatic arthritis receiving anti-TNF therapy. In addition, we reviewed cytokines and chemokines which, directly or indirectly, activate OCPs and enhance their differentiation potential, thus mediating osteoresorption. Control of the activity and migratory behaviour of OCPs as well as the identification of crucial bone/joint chemotactic mediators represent promising therapeutic targets in arthritis.

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Acknowledgments

This work was supported by the University of Zagreb Research Grant (402-08/13-03/37).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Physiology and Immunology, University of Zagreb School of Medicine, Šalata 3b, Zagreb, 10000, Croatia

    Alan Šućur, Tomislav Kelava & Danka Grčević

  2. Laboratory for Molecular Immunology, University of Zagreb School of Medicine, Šalata 12, Zagreb, 10000, Croatia

    Alan Šućur, Vedran Katavić, Tomislav Kelava & Danka Grčević

  3. Department of Anatomy, University of Zagreb School of Medicine, Šalata 11, Zagreb, 10000, Croatia

    Vedran Katavić & Natasa Kovačić

  4. Department of Rheumatology, Physical Medicine and Rehabilitation, Clinical Hospital Center “Sisters of Mercy”, University of Zagreb School of Medicine, Vinogradska cesta 29, Zagreb, 10000, Croatia

    Zrinka Jajić

  5. Garvan Institute of Medical Research, 384 Victoria Street, Sydney, NSW, 2020, Australia

    Natasa Kovačić

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  6. Danka Grčević
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Correspondence to Danka Grčević.

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Šućur, A., Katavić, V., Kelava, T. et al. Induction of osteoclast progenitors in inflammatory conditions: key to bone destruction in arthritis. International Orthopaedics (SICOT) 38, 1893–1903 (2014). https://doi.org/10.1007/s00264-014-2386-y

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  • DOI: https://doi.org/10.1007/s00264-014-2386-y

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