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

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  1. Development of a downstream process for the production of an inactivated whole hepatitis C virus vaccine

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  2. Simvastatin improves mitochondrial respiration in peripheral blood cells

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  3. Tumor cell MT1-MMP is dispensable for osteosarcoma tumor growth, bone degradation and lung metastasis

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  1. Maintenance of muscle strength following a one-year resistance training program in older adults

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  2. The influence of prolonged strength training upon muscle and fat in healthy and chronically diseased older adults

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  3. The effect of 4 months exercise training on systemic biomarkers of cartilage and bone turnover in hip osteoarthritis patients

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  4. Early development of tendinopathy in humans: Sequence of pathological changes in structure and tissue turnover signaling

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  5. The influence of fibrillin-1 and physical activity upon tendon tissue morphology and mechanical properties in mice

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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 CLOCKΔ19 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.

Original languageEnglish
JournalScientific Reports
Volume4
Pages (from-to)5183
ISSN2045-2322
DOIs
Publication statusPublished - 2014

ID: 44863200