ArticleScientific reports2014
Gremlin-2 is a BMP antagonist that is regulated by the circadian clock.
Article in Scientific reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
42 citing papers in PubMed, 67 citations in OpenAlex.
- Investigating circadian clock gene expression in human tendon biopsies from acute exercise and immobilization studies.European journal of applied physiology · 2019Trial
- Load magnitude affects patellar tendon mechanical properties but not collagen or collagen cross-linking after long-term strength training in older adults.BMC geriatrics · 2019Trial
- Pathogenesis of Shoulder Calcific Tendinopathy.International journal of molecular sciences · 2026Review
- Targeting Circadian Rhythm for the Regulation of Skin Collagen Metabolism.Journal of cosmetic dermatology · 2026Article
- Article
- Circadian regulation of extracellular vesicle biogenesis, composition, and release.Npj biological timing and sleep · 2025Review
- Role of the tendon circadian clock in tendinopathy and implications for therapeutics.International journal of experimental pathology · 2025Review
- Disruption of day-to-night changes in circadian gene expression with chronic tendinopathy.The Journal of physiology · 2024Article
- Circadian Regulation of Bone Remodeling.International journal of molecular sciences · 2024Review
- Craniofacial chondrogenesis in organoids from human stem cell-derived neural crest cells.iScience · 2024Article
- A topographic atlas defines developmental origins of cell heterogeneity in the human embryonic lung.Nature cell biology · 2023Article
- Dynamic movement and turnover of extracellular matrices during tissue development and maintenance.Fly · 2022Review
- Selection signature analyses and genome-wide association reveal genomic hotspot regions that reflect differences between breeds of horse with contrasting risk of degenerative suspensory ligament desmitis.G3 (Bethesda, Md.) · 2022Article
- Optimizing Tenogenic Differentiation of Equine Adipose-Derived Mesenchymal Stem Cells (eq-ASC) Using TGFB3 Along with BMP Antagonists.Cell journal · 2022Article
- Circadian regulation of protein cargo in extracellular vesicles.Science advances · 2022Article
- Circadian rhythms affect bone reconstruction by regulating bone energy metabolism.Journal of translational medicine · 2021Review
- Drivers of phenotypic variation in cartilage: Circadian clock genes.Journal of cellular and molecular medicine · 2021Review
- LncRNA DNM3OS regulates GREM2 via miR-127-5p to suppress early chondrogenic differentiation of rat mesenchymal stem cells under hypoxic conditions.Cellular & molecular biology letters · 2021Article
- Tendon Extracellular Matrix Assembly, Maintenance and Dysregulation Throughout Life.Advances in experimental medicine and biology · 2021Review
- Shaping Waves of Bone Morphogenetic Protein Inhibition During Vascular Growth.Circulation research · 2020Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
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 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.