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Development. 2018 Mar 12;145(5). pii: dev153460. doi: 10.1242/dev.153460.

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

Author information

1
Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Uttar Pradesh 208016, India.
2
Department of Zoology, School of Natural Sciences, Trinity College Dublin, Dublin 2, Ireland.
3
Department of Zoology, School of Natural Sciences, Trinity College Dublin, Dublin 2, Ireland abandopa@iitk.ac.in paula.murphy@tcd.ie.
4
Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Uttar Pradesh 208016, India abandopa@iitk.ac.in paula.murphy@tcd.ie.

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.

KEYWORDS:

Articular cartilage; Immobilization; Joint development; Mechanoregulation; Mechanosensitivity; Muscle contraction; Wnt/BMP signaling

PMID:
29467244
DOI:
10.1242/dev.153460
[Indexed for MEDLINE]
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