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Gremlin-2 is a BMP antagonist that is regulated by the circadian clock

Yeung, C-YC, Gossan, N, Lu, Y, Hughes, ATL, Hensman, JJ, Bayer, ML, Kjaer, M, Kadler, KE and Meng, Q-J (2014) Gremlin-2 is a BMP antagonist that is regulated by the circadian clock. Scientific Reports, 4. ISSN 2045-2322

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Abstract

Tendons are prominent members of the family of fibrous connective tissues (FCTs), which collectively are the most abundant tissues in vertebrates and have crucial roles in transmitting mechanical force and linking organs. Tendon diseases are among the most common arthropathy disorders; thus knowledge of tendon gene regulation is essential for a complete understanding of FCT biology. Here we show autonomous circadian rhythms in mouse tendon and primary human tenocytes, controlled by an intrinsic molecular circadian clock. Time-series microarrays identified the first circadian transcriptome of murine tendon, revealing that 4.6% of the transcripts (745 genes) are expressed in a circadian manner. One of these genes was Grem2, which oscillated in antiphase to BMP signaling. Moreover, recombinant human Gremlin-2 blocked BMP2-induced phosphorylation of Smad1/5 and osteogenic differentiation of human tenocytes in vitro.We observed dampened Grem2 expression, deregulated BMP signaling, and spontaneously calcifying tendons in young CLOCKD19 arrhythmic mice and aged wild-type mice. Thus, disruption of circadian control, through mutations or aging, of Grem2/BMP signaling becomes a new focus for the study of calcific tendinopathy, which affects 1-in-5 people over the age of 50 years.

Item Type: Article
Uncontrolled Keywords: 0601 Biochemistry and Cell Biology, 0299 Other Physical Sciences
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions: Natural Sciences and Psychology
Publisher: Nature Publishing Group
Related URLs:
Date Deposited: 05 Sep 2019 10:42
Last Modified: 05 Sep 2019 10:45
DOI or Identification number: 10.1038/srep05183
URI: http://researchonline.ljmu.ac.uk/id/eprint/11283

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