A novel miR17/protein tyrosine phosphatase-oc/EphA4 regulatory axis of osteoclast activity

Archives of Biochemistry and Biophysics
Kin-Hing William Lau, Matilda H-C Sheng

Abstract

Information about the molecular mechanisms leading to the activation of the osteoclast is relatively limited. While there is compelling evidence that the signaling mechanisms of Src and integrin β3 are essential for osteoclast activation, the regulation of these two signaling mechanisms is not fully understood. In this review, evidence supporting a novel regulatory axis of osteoclast activation that plays an upstream regulatory role in both the Src and integrin β3 signaling during osteoclast activation is discussed. This regulatory axis contains three unique components: a structurally unique transmembrane protein-tyrosine phosphatase, PTP-oc, EphA4, and miR17. In the first component, PTP-oc activates the Src signaling through dephosphorylation of the inhibitory tyr-527 of Src. This in turn activates the integrin β3 signaling, enhances the JNK2/NFκB signaling, promotes the ITAM/Syk signaling, and suppresses the ITIM/Shp1 signaling; the consequence of which is activation of the osteoclast. In the second component, EphA4 inhibits osteoclast activity by suppressing the integrin β3 signaling. PTP-oc relieves the suppressive actions of EphA4 by directly dephosphorylating EphA4. In the third component, PTP-oc expression is negatively ...Continue Reading

Citations

Aug 20, 2019·British Journal of Pharmacology·Margherita PuppoPhilippe Clézardin
Sep 11, 2020·Stem Cells International·Yi ZhaoWeiran Li
Nov 20, 2020·Bone·Megan M WeivodaDavid G Monroe

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