Skip to main content

Thank you for visiting 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.

Closing the loop on the bone-resorbing osteoclast

A new study shows in mice that tumor necrosis factor (TNF) superfamily member 11 (TNFSF11, also known as RANKL), which stimulates osteoclasts to remove bone, binds to the G-protein-coupled receptor LGR4 to prevent excessive bone removal. In mouse models of osteoporosis, a recombinant LGR4 ectodomain reduces bone loss.

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

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: The osteoclast negative-feedback loop.


  1. Häusler, K.D. et al. J. Bone Miner. Res. 19, 1873–1881 (2004).

    Article  Google Scholar 

  2. Luo, J. et al. Nat. Med 22, 539–546 (2016).

    CAS  Article  Google Scholar 

  3. Luo, J. et al. Development 136, 2747–2756 (2009).

    CAS  Article  Google Scholar 

  4. Sun, L. et al. Cell 125, 247–260 (2006).

    CAS  Article  Google Scholar 

  5. Abe, E. et al. Cell 115, 151–162 (2003).

    CAS  Article  Google Scholar 

  6. Ferlin, A., Pepe, A., Facciolli, A., Gianesello, L. & Foresta, C. Bone 46, 504–513 (2010).

    CAS  Article  Google Scholar 

  7. Yi, H., Wang, J., Kavallaris, M. & Yingzi-Wang, J. Blood 122, abstr. 887 (2013).

  8. Hur, E.M. & Zhou, F.Q. Nat. Rev. Neurosci. 11, 539–551 (2010).

    CAS  Article  Google Scholar 

  9. Li, Z., Zhang, W. & Mulholland, M.W. Front. Endocrinol. (Lausanne) 6, 131 (2015).

    PubMed Central  Google Scholar 

  10. Wu, C. et al. Nat. Commun. 5, 3149 (2014).

    Article  Google Scholar 

  11. Krausova, M. & Korinek, V. Cell. Signal. 26, 570–579 (2014).

    CAS  Article  Google Scholar 

  12. Du, B. et al. J. Biol. Chem. 288, 15131–15141 (2013).

    CAS  Article  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Mone Zaidi.

Ethics declarations

Competing interests

Mone Zaidi has consulted and/or consults for Merck, Novartis, Roche, Alexion, Gershon Lehman Group and Guidepoint on issues related to osteoporosis and its treatment. A patent relating to the effects of follicle-stimulating hormone on bone has been granted, and any proceeds to the Icahn School of Medicine at Mount Sinai from licensing or royalty will be shared with Dr. Zaidi.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Zaidi, M., Iqbal, J. Closing the loop on the bone-resorbing osteoclast. Nat Med 22, 460–461 (2016).

Download citation

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


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