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Bone diseases

Sclerostin neutralization—a viable pathway for OPPG?

Nature Reviews Rheumatology volume 10, page 4 (2014)Cite this article

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The anabolic effects of inhibiting sclerostin—a negative regulator of the Wnt bone forming pathway—can improve bone mass in the absence of low-density lipoprotein receptor-related protein 5 (LRP5), a major sclerostin receptor. “We thought that inhibiting sclerostin would have a generally modest bone building effect in Lrp5 knockout mice,” explains Alexander Robling, lead author of the article. He continues, “when the study was complete we were surprised, but very pleased, that the treatment had resulted in such a dramatic increase in bone formation and bone mineral density.”

Here, Kedlaya and colleagues measured bone properties in various knockout mouse models. Mice lacking both Lrp5 and sclerostin had stronger bones than mice lacking Lrp5 only, which suggests that a deficiency of sclerostin improves the properties of bone through pathways that do not require Lrp5. In addition, the researchers tested antianabolic responses by treating Lrp5-deficient mice with an anti-sclerostin antibody. Sclerostin depletion resulted in increased bone mineral density and bone formation rates in mice with and without Lrp5. “Our results indicated that LRP6 likely has a significant role as a sclerostin receptor, probably even more so when LRP5 is absent,” says Robling.

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References

  1. Kedlaya, R. et al. Sclerostin inhibition reverses skeletal fragility in an Lrp5-deficient mouse model of OPPG syndrome. Sci. Transl. Med. 5, 211ra158 (2013)

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  1. Bryony Jones
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Jones, B. Sclerostin neutralization—a viable pathway for OPPG?. Nat Rev Rheumatol 10, 4 (2014). https://doi.org/10.1038/nrrheum.2013.189

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  • DOI: https://doi.org/10.1038/nrrheum.2013.189

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