Precise spatial restriction of BMP signaling in developing joints is perturbed upon loss of embryo movement

Development
Pratik Narendra Pratap SinghAmitabha Bandyopadhyay

Abstract

Dynamic mechanical loading of synovial joints is necessary for normal joint development, as evidenced in certain clinical conditions, congenital disorders and animal models where dynamic muscle contractions are reduced or absent. Although the importance of mechanical forces on joint development is unequivocal, little is known about the molecular mechanisms involved. Here, using chick and mouse embryos, we observed that molecular changes in expression of multiple genes analyzed in the absence of mechanical stimulation are consistent across species. Our results suggest that abnormal joint development in immobilized embryos involves inappropriate regulation of Wnt and BMP signaling during definition of the emerging joint territories, i.e. reduced β-catenin activation and concomitant upregulation of pSMAD1/5/8 signaling. Moreover, dynamic mechanical loading of the developing knee joint activates Smurf1 expression; our data suggest that Smurf1 insulates the joint region from pSMAD1/5/8 signaling and is essential for maintenance of joint progenitor cell fate.

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Citations

Jul 13, 2019·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Vivien SotiriouNiamh C Nowlan
Nov 21, 2019·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Claire A SheaPaula Murphy
Mar 5, 2020·Development·Jake Cornwall Scoones, Tom W Hiscock
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Sep 27, 2018·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Rebecca A RolfePaula Murphy
Sep 27, 2018·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Elizabeth A LawrenceChrissy L Hammond
Sep 27, 2018·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Cristian ParisiNiamh C Nowlan
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Dec 15, 2020·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Gabriel L GaleaPhilippa Francis-West
Feb 27, 2021·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Haodong Zhou
Mar 28, 2021·Disease Models & Mechanisms·Rebecca A RolfePaula Murphy
Aug 24, 2021·Disease Models & Mechanisms·Rebecca A RolfePaula Murphy

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