ArticleProceedings of the National Academy of Sciences of the United States of America2015
Transcription factor Hes1 modulates osteoarthritis development in cooperation with calcium/calmodulin-dependent protein kinase 2.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 97 citations in OpenAlex.
- Obesity-induced oleic acid metabolic dysregulation may exacerbate osteoarthritis through the degradation of SOX9.Cellular and molecular life sciences : CMLS · 2026Article
- HES3-dependent regulatory functions in development and fusion-positive rhabdomyosarcoma.bioRxiv : the preprint server for biology · 2026Article
- DAPT Mitigates Osteoarthritic Cartilage Degeneration and Enhances Articular Repair Through Targeted Modulation of the Gucy1a3 and Notch Signaling Axis.Drug design, development and therapy · 2026Article
- The Notch signaling pathway in regulating bone and cartilage homeostasis: novel insights into the pathogenesis and therapeutics of osteoarthritis.Cell communication and signaling : CCS · 2025Review
- Advances in the pathology and treatment of osteoarthritis.Journal of advanced research · 2025Review
- Selenium deficiency exacerbates cartilage degradation caused by HT-2 toxin via notch signaling pathway activation.European journal of nutrition · 2025Article
- Blockade of the Notch Pathway by Inhibition of Fucosylation Ameliorates Chondrocyte Inflammation and Extracellular Matrix Degradation.Journal of inflammation research · 2025Article
- The pivotal role of the Hes1/Piezo1 pathway in the pathophysiology of glucocorticoid-induced osteoporosis.JCI insight · 2024Article
- A high throughput cell stretch device for investigating mechanobiologyAPL bioengineering · 2024Article
- Hypertrophic chondrocytes at the junction of musculoskeletal structures.Bone reports · 2023Article
- Bulk RNA-seq analyses of mandibular condylar cartilage in a post-traumatic TMJ osteoarthritis rabbit model.Orthodontics & craniofacial research · 2023Article
- Cartilage-specificAnnals of the rheumatic diseases · 2023Article
- MYL3 protects chondrocytes from senescence by inhibiting clathrin-mediated endocytosis and activating of Notch signaling.Nature communications · 2023Article
- The role of apoptosis in the pathogenesis of osteoarthritis.International orthopaedics · 2023Review
- The Role of Selenium-Mediated Notch/Hes1 Signaling Pathway in Kashin-Beck Disease Patients and Cartilage Injury Models.Biological trace element research · 2023Article
- Wnt signalling in the articular cartilage: A matter of balance.International journal of experimental pathology · 2023Review
- Osteoarthritis: pathogenic signaling pathways and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- The Role of Cartilage Stem/Progenitor Cells in Cartilage Repair in Osteoarthritis.Current stem cell research & therapy · 2023Article
- Review
- Targeting the transcription factor HES1 by L-menthol restores protein phosphatase 6 in keratinocytes in models of psoriasis.Nature communications · 2022Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Notch signaling modulates skeletal formation and pathogenesis of osteoarthritis (OA) through induction of catabolic factors. Here we examined roles of Hes1, a transcription factor and important target of Notch signaling, in these processes. SRY-box containing gene 9 (Sox9)-Cre mice were mated with Hes1(fl/fl) mice to generate tissue-specific deletion of Hes1 from chondroprogenitor cells; this deletion caused no obvious abnormality in the perinatal period. Notably, OA development was suppressed when Hes1 was deleted from articular cartilage after skeletal growth in type II collagen (Col2a1)-Cre(ERT);Hes1(fl/fl) mice. In cultured chondrocytes, Hes1 induced metallopeptidase with thrombospondin type 1 motif, 5 (Adamts5) and matrix metalloproteinase-13 (Mmp13), which are catabolic enzymes that break down cartilage matrix. ChIP-seq and luciferase assays identified Hes1-responsive regions in intronic sites of both genes; the region in the ADAMTS5 gene contained a typical consensus sequence for Hes1 binding, whereas that in the MMP13 gene did not. Additionally, microarray analysis, together with the ChIP-seq, revealed novel Hes1 target genes, including Il6 and Il1rl1, coding a receptor for IL-33. We further identified calcium/calmodulin-dependent protein kinase 2δ (CaMK2δ) as a cofactor of Hes1; CaMK2δ was activated during OA development, formed a protein complex with Hes1, and switched it from a transcriptional repressor to a transcriptional activator to induce cartilage catabolic factors. Therefore, Hes1 cooperated with CaMK2δ to modulate OA pathogenesis through induction of catabolic factors, including Adamts5, Mmp13, Il6, and Il1rl1. Our findings have contributed to further understanding of the molecular pathophysiology of OA, and may provide the basis for development of novel treatments for joint disorders.
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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 OpenQuestion graph.