ArticleScientific reports2016
Notch signaling indirectly promotes chondrocyte hypertrophy via regulation of BMP signaling and cell cycle arrest.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 39 citations in OpenAlex.
- Comparison of bone age between both limbs in patients with congenital hemihyperplasia or hemihypoplasia: A retrospective study.Journal of children's orthopaedics · 2026Article
- Chondrocytes in fracture healing: A review of chondrocyte journey.Chinese medical journal · 2026Review
- Unraveling the Potential ofBiomacromolecules · 2026Article
- Molecular Mechanisms of Chondrocyte Hypertrophy Mediated by Physical Cues and Therapeutic Strategies in Osteoarthritis.International journal of molecular sciences · 2026Review
- Role of Notch signaling pathway in joint homeostasis and osteoarthritis.Frontiers in bioengineering and biotechnology · 2026Review
- 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
- Crosstalk between the circadian clock, intestinal stem cell niche, and epithelial cell fate decision.Genes & diseases · 2025Review
- Article
- S-Nitrosylation of NOTCH1 Regulates Mesenchymal Stem Cells Differentiation Into Hepatocyte-Like Cells by Inhibiting Notch Signalling Pathway.Journal of cellular and molecular medicine · 2024Article
- "A Friend Among Strangers" or the Ambiguous Roles of Runx2.Biomolecules · 2024Review
- The involvement of signaling pathways in the pathogenesis of osteoarthritis: An update.Journal of orthopaedic translation · 2024Review
- Proteoglycan inhibition of canonical BMP-dependent cartilage maturation delays endochondral ossification.Development (Cambridge, England) · 2024Article
- Hypertrophic chondrocytes at the junction of musculoskeletal structures.Bone reports · 2023Article
- Long noncoding RNA (lncRNA)Genes & diseases · 2023Review
- Review
- Supplementation of articular cartilage-derived chondroprogenitors with bone morphogenic protein-9 enhances chondrogenesis without affecting hypertrophy.Biotechnology letters · 2022Article
- Notch signaling regulates neural stem cell quiescence entry and exit in Drosophila.Development (Cambridge, England) · 2022Article
- Pleiotropic Roles of NOTCH1 Signaling in the Loss of Maturational Arrest of Human Osteoarthritic Chondrocytes.International journal of molecular sciences · 2021Article
- Research advances in cartilage stem cells markers and induced differentiation.Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2021Review
- Molecular Mechanisms of Chondrocyte Proliferation and Differentiation.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
Cell cycle regulation is critical for chondrocyte differentiation and hypertrophy. Recently we identified the Notch signaling pathway as an important regulator of chondrocyte proliferation and differentiation during mouse cartilage development. To investigate the underlying mechanisms, we assessed the role for Notch signaling regulation of the cell cycle during chondrocyte differentiation. Real-time RT-PCR data showed that over-expression of the Notch Intracellular Domain (NICD) significantly induced the expression of p57, a cell cycle inhibitor, in chondrocytes. Flow cytometric analyses further confirmed that over-expression of NICD in chondrocytes enhances the G0/G1 cell cycle transition and cell cycle arrest. In contrast, treatment of chondrocytes with the Notch inhibitor, DAPT, decreased both endogenous and BMP2-induced SMAD 1/5/8 phosphorylation and knockdown of SMAD 1/5/8 impaired NICD-induced chondrocyte differentiation and p57 expression. Co-immunoprecipitation using p-SMAD 1/5/8 and NICD antibodies further showed a strong interaction of these proteins during chondrocyte maturation. Finally, RT-PCR and Western blot results revealed a significant reduction in the expression of the SMAD-related phosphatase, PPM1A, following NICD over-expression. Taken together, our results demonstrate that Notch signaling induces cell cycle arrest and thereby initiates chondrocyte hypertrophy via BMP/SMAD-mediated up-regulation of p57.
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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 OpenQuestion graph.