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

Yeung, Ching Yan Chloé and Gossan, Nicole and Lu, Yinhui and Hughes, Alun and Hensman, James J. and Bayer, Monika L. and Kjær, Michael and Kadler, Karl E. and Meng, Qing Jun (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 CLOCKÎ "19 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:
Journal Article
Journal or Publication Title:
Scientific Reports
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/1000
Subjects:
ID Code:
84348
Deposited By:
Deposited On:
25 Jan 2017 14:28
Refereed?:
Yes
Published?:
Published
Last Modified:
30 Sep 2020 06:23