ArticleArthritis & rheumatology (Hoboken, N.J.)2016
Regulation of Cholesterol Homeostasis by Hedgehog Signaling in Osteoarthritic Cartilage.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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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.
The trial behind it
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
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- The association between statin use and osteoarthritis-related outcomes: An updated systematic review and meta-analysis.Frontiers in pharmacology · 2022Pooled it
- Statin use and knee osteoarthritis progression: Results from a post-hoc analysis of the SEKOIA trial.Joint bone spine · 2018Trial
- Cross-talk between GLI2 and FOXC1 promotes osteoarthritis-like cartilage catabolism and in vivo joint degeneration.Functional & integrative genomics · 2026Article
- Platelet-rich plasma in cartilage repair: biological mechanisms and clinical perspectives.Frontiers in sports and active living · 2026Review
- The role of metabolites in the progression of osteoarthritis: Mechanisms and advances in therapy.Journal of orthopaedic translation · 2025Review
- Dyslipidemia induced inflammation mediated the association between obesity and Osteoarthritis: a population-based study.BMC public health · 2024Article
- Hyperactivation of Hedgehog signaling impedes myelin development and repair via cholesterol dysregulation in oligodendrocytes.iScience · 2024Article
- Article
- RPL35 downregulated by mechanical overloading promotes chondrocyte senescence and osteoarthritis development via Hedgehog-Gli1 signaling.Journal of orthopaedic translation · 2024Article
- Characterizing hedgehog pathway features in senescence associated osteoarthritis through Integrative multi-omics and machine learning analysis.Frontiers in genetics · 2024Article
- GLI1 facilitates collagen-induced arthritis in mice by collaborative regulation of DNA methyltransferases.eLife · 2023Article
- How are Aging and Osteoarthritis Related?Aging and disease · 2023Review
- Nutrient metabolism of the nucleus pulposus: A literature review.North American Spine Society journal · 2023Article
- Resveratrol Improves the Progression of Osteoarthritis by Regulating the SIRT1-FoxO1 Pathway-Mediated Cholesterol Metabolism.Mediators of inflammation · 2023Article
- Role of the hedgehog signaling pathway in rheumatic diseases: An overview.Frontiers in immunology · 2022Review
- Cholesterol and Hedgehog Signaling: Mutual Regulation and Beyond.Frontiers in cell and developmental biology · 2022Review
- Osteoblasts impair cholesterol synthesis in chondrocytes via Notch1 signalling.Cell proliferation · 2021Article
- Implications of zonal architecture on differential gene expression profiling and altered pathway expressions in mandibular condylar cartilage.Scientific reports · 2021Article
- Enchondromatosis and Growth Plate Development.Current osteoporosis reports · 2021Review
- Regulation of gene expression by MF63, a selective inhibitor of microsomal PGE synthase 1 (mPGES1) in human osteoarthritic chondrocytes.British journal of pharmacology · 2020Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveWith no effective therapies to attenuate cartilage degeneration in osteoarthritis (OA), the result is pain and disability. Activation of hedgehog (HH) signaling causes changes related to the progression of OA, with higher levels of Gli-mediated transcriptional activation associated with increased disease severity. To elucidate the mechanism through which this occurs, this study sought to identify genes regulated by HH signaling in human OA chondrocytes.
methodsUsing human OA cartilage samples, microarray analyses were performed to detect changes in gene expression when the HH pathway was modulated. Results were analyzed for differentially expressed genes, grouped into functional networks, and validated in independent samples. To investigate the effects of chondrocyte-specific sterol accumulation, we generated mice lacking Insig1 and Insig2, which are major negative regulators of cholesterol homeostasis, under Col2a1 regulatory elements.
resultsHH signaling was found to regulate genes that govern cholesterol homeostasis, and this led to alterations in cholesterol accumulation in chondrocytes. A higher level of Gli-mediated transcription resulted in accumulation of intracellular cholesterol. In genetically modified mice, chondrocyte-specific cholesterol accumulation was associated with an OA phenotype. Reducing cholesterol accumulation attenuated the severity of OA in mice in vivo and decreased the expression of proteases in human OA cartilage in vitro.
conclusionHH signaling regulates cholesterol homeostasis in chondrocytes, and intracellular cholesterol accumulation contributes to the severity of OA. Our findings have therapeutic implications, since reduction of HH signaling reversed cholesterol accumulation and statin treatment attenuated cartilage degeneration.
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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.