ArticleJournal of bone and mineral metabolism2022
Disruption of the mouse Bmal1 locus promotes heterotopic ossification with aging via TGF-beta/BMP signaling.
Article in Journal of bone and mineral metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- Tendon stem/progenitor cells in heterotopic ossification: functional regulation, molecular mechanisms and targeted therapeutic strategies.Journal of orthopaedic translation · 2026Review
- Integrating TWAS, chemical-genomic networks, and experimental models: melatonin as a ferroptosis inhibitor in osteoarthritis therapy.Clinical rheumatology · 2026Article
- Dual roles of circadian clock proteins in development and adult homeostasis.Npj biological timing and sleep · 2026Review
- Preclinical validation of TGFβ inhibitors as a novel therapeutic strategy for post-traumatic heterotopic ossification.Scientific reports · 2025Article
- Signaling pathway mechanisms of circadian clock gene Bmal1 regulating bone and cartilage metabolism: a review.Bone research · 2025Review
- Progress in understanding how clock genes regulate aging and associated metabolic processes.Frontiers in physiology · 2025Review
- Targeting fibroblasts in pathological bone formation: mechanisms and treatments.Frontiers in cell and developmental biology · 2025Review
- Enpp1 mutations promote upregulation of hedgehog signaling in heterotopic ossification with aging.Journal of bone and mineral metabolism · 2024Article
- A new perspective on intervertebral disc calcification-from bench to bedside.Bone research · 2024Review
- Loss of function mutation in Ank causes aberrant mineralization and acquisition of osteoblast-like-phenotype by the cells of the intervertebral disc.Cell death & disease · 2023Article
- Molecular regulation after mucosal injury and regeneration in ulcerative colitis.Frontiers in molecular biosciences · 2022Review
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Authors and funding
11 authors at 1 institution in 1 country.
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Abstract
introductionHeterotopic ossification of tendons and ligaments is a painful and debilitating disease with no effective treatment. Although aging has been reported to be correlated with the occurrence and development of this disease, the mechanism remains unknown. MATERIALS AND
methodsIn the present study, we generated Bmal1-/- mice, which disrupted the circadian clock and displayed premature aging, as an aging model to explore the role of Bmal1 in TGF-beta (β)/BMP signaling in progressive heterotopic ossification of tendons and ligaments with aging.
resultsWe first confirmed that BMAL1 expression is downregulated in human fibroblasts from ossification of the posterior longitudinal ligament using online datasets. Bmal1 deficiency in mice caused significantly progressive heterotopic ossification with aging starting at week 6, notably in the Achilles tendons and posterior longitudinal ligaments. Ossification of the Achilles tendons was accompanied by progressive motor dysfunction of the ankle joint. Histology and immunostaining showed markedly increased endochondral ossification in the posterior longitudinal ligaments and Achilles tendons of Bmal1-/- mice. Ligament-derived Bmal1-/- fibroblasts showed an osteoblast-like phenotype, upregulated osteogenic and chondrogenic markers, and activated TGFβ/BMP signaling, which was enhanced by TGFβ1 stimulation. Furthermore, Bmal1-/- mouse embryonic fibroblasts had a stronger potential for osteogenic differentiation with activation of TGFβ/BMP signaling.
conclusionsThese findings demonstrated that Bmal1 negatively regulates endochondral ossification in heterotopic ossification of tendons and ligaments with aging via TGFβ/BMP signaling, thereby identifying a new regulatory mechanism in age-related heterotopic ossification of tendons and ligaments.
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