Research ArticlePhysiology

Protein kinase N3 promotes bone resorption by osteoclasts in response to Wnt5a-Ror2 signaling

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Sci. Signal.  29 Aug 2017:
Vol. 10, Issue 494, eaan0023
DOI: 10.1126/scisignal.aan0023

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Bone breakdown

To resorb bone, osteoclasts must remodel the cytoskeleton to form actin rings. Thus, understanding the pathways that control actin ring formation in osteoclasts could reveal potential therapeutic targets for reversing losses in bone density in diseases such as osteoporosis. Using genetically manipulated mice and cells derived from these mice, Uehara et al. characterized a pathway that stimulated bone resorption by osteoclasts. Binding of Wnt5a to one of its receptors, Ror2, activated the small GTPase Rho, its effector Pkn3, and c-Src, a kinase that is required for actin ring formation. The authors note that several of these proteins are implicated in tumor metastasis and that this signaling pathway may operate in metastasizing cancer cells.