Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • News & Views
  • Published:

Bone

Do all Paget disease risk genes incriminate the osteoclast?

A key component of Paget disease of bone is a localized increase in osteoclastic activity, which might be attributable, in part, to mutations in the sequestosome 1 gene. A study has identified three new genes that regulate osteoclasts and are implicated in Paget disease; however, the clinical utility of these findings remains questionable.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

References

  1. Rhodes, E. C. et al. Sequestosome 1 (SQSTM1) mutations in Paget's disease of bone from the United States. Calcif. Tissue Int. 82, 271–277 (2008).

    Article  CAS  Google Scholar 

  2. Gennari, L. et al. SQSTM1 gene analysis and gene-environment interaction in Paget's disease of bone. J. Bone Miner. Res. 25, 1375–1384 (2010).

    Article  CAS  Google Scholar 

  3. Neumann, M., Tolnay, M. & Mackenzie, I. R. The molecular basis of frontotemporal dementia. Expert Rev. Mol. Med. 11, e23 (2009).

    Article  Google Scholar 

  4. Merchant, A. et al. Somatic mutations in SQSTM1 detected in affected tissues from patients with sporadic Paget's disease of bone. J. Bone Miner. Res. 24, 484–494 (2009).

    Article  CAS  Google Scholar 

  5. Matthews, B. G. et al. Absence of somatic SQSTM1 mutations in Paget's disease of bone. J. Clin. Endocrinol. Metab. 94, 691–694 (2009).

    Article  CAS  Google Scholar 

  6. Albagha, O. M. et al. Genome-wide association study identifies variants at CSF1, OPTN and TNFRSF11A as genetic risk factors for Paget's disease of bone. Nat. Genet. 42, 520–524 (2010).

    Article  CAS  Google Scholar 

  7. Neale, S. D., Schulze, E., Smith, R. & Athanasou, N. A. The influence of serum cytokines and growth factors on osteoclast formation in Paget's disease. QJM 95, 233–240 (2002).

    Article  CAS  Google Scholar 

  8. Hughes, A. E. et al. Mutations in TNFRSF11A, affecting the signal peptide of RANK, cause familial expansile osteolysis. Nat. Genet. 24, 45–48 (2000).

    Article  CAS  Google Scholar 

  9. Pomerantz, M. M. et al. The 8q24 cancer risk variant rs6983267 shows long-range interaction with MYC in colorectal cancer. Nat. Genet. 41, 882–884 (2009).

    Article  CAS  Google Scholar 

  10. Rezaie, T. et al. Adult-onset primary open-angle glaucoma caused by mutations in optineurin. Science 295, 1077–1079 (2002).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Frederick R. Singer.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Singer, F., Leach, R. Do all Paget disease risk genes incriminate the osteoclast?. Nat Rev Rheumatol 6, 502–503 (2010). https://doi.org/10.1038/nrrheum.2010.137

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrrheum.2010.137

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing