ArticleArthritis research & therapy2013
GREM1, FRZB and DKK1 mRNA levels correlate with osteoarthritis and are regulated by osteoarthritis-associated factors.
Article in Arthritis research & therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 92 citations in OpenAlex.
- Metabolic programming of mesenchymal stromal cells by oxygen tension directs chondrogenic cell fate.Proceedings of the National Academy of Sciences of the United States of America · 2014Trial
- Advancing Intervertebral Disc Biology via Omics: Implications for Nucleus Pulposus Progenitor Cell-Based Regeneration.JOR spine · 2025Review
- An Organ-on-Chip Platform for Strain-Controlled, Tissue-Specific Compression of Cartilage and Mineralized Osteochondral Interface to Study Mechanical Overloading in Osteoarthritis.Advanced healthcare materials · 2025Article
- Insights into the bone morphogenetic protein signaling in musculoskeletal disorders: Mechanisms and crosstalk.Journal of orthopaedic translation · 2025Review
- Suppressing Chondrocyte Hypertrophy to Build Better Cartilage.Bioengineering (Basel, Switzerland) · 2023Review
- Wnt signalling in the articular cartilage: A matter of balance.International journal of experimental pathology · 2023Review
- Characterization of a novel corticosterone response gene inFrontiers in endocrinology · 2023Article
- Harnessing joint distraction for the treatment of osteoarthritis: a bibliometric and visualized analysis.Frontiers in bioengineering and biotechnology · 2023Article
- Review
- An integrated in silico-in vitro approach for identifying therapeutic targets against osteoarthritis.BMC biology · 2022Article
- Histone H3K27 demethylase UTX compromises articular chondrocyte anabolism and aggravates osteoarthritic degeneration.Cell death & disease · 2022Article
- Protective role of microRNA-23a/b-3p inhibition against osteoarthritis through Gremlin1-depenent activation of TGF-β/smad signaling in chondrocytesa.Inflammopharmacology · 2022Article
- Perturbation of Wnt/β-catenin signaling and sexual dimorphism in non-alcoholic fatty liver disease.Hepatology research : the official journal of the Japan Society of Hepatology · 2022Article
- Gremlin-1 and BMP-4 Overexpressed in Osteoarthritis Drive an Osteochondral-Remodeling Program in Osteoblasts and Hypertrophic Chondrocytes.International journal of molecular sciences · 2022Article
- Primary Cilia: A Cellular Regulator of Articular Cartilage Degeneration.Stem cells international · 2022Review
- Joint distraction for osteoarthritis: clinical evidence and molecular mechanisms.Nature reviews. Rheumatology · 2022Review
- Enhanced Extracellular Matrix Breakdown Characterizes the Early Distraction Phase of Canine Knee Joint Distraction.Cartilage · 2021Article
- PRIMUS: Comprehensive proteomics of mouse intervertebral discs that inform novel biology and relevance to human disease modelling.Matrix biology plus · 2021Article
- Article
- Human pluripotent stem cell-derived cartilaginous organoids promote scaffold-free healing of critical size long bone defects.Stem cell research & therapy · 2021Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionOsteoarthritis is, at least in a subset of patients, associated with hypertrophic differentiation of articular chondrocytes. Recently, we identified the bone morphogenetic protein (BMP) and wingless-type MMTV integration site (WNT) signaling antagonists Gremlin 1 (GREM1), frizzled-related protein (FRZB) and dickkopf 1 homolog (Xenopus laevis) (DKK1) as articular cartilage's natural brakes of hypertrophic differentiation. In this study, we investigated whether factors implicated in osteoarthritis or regulation of chondrocyte hypertrophy influence GREM1, FRZB and DKK1 expression levels.
methodsGREM1, FRZB and DKK1 mRNA levels were studied in articular cartilage from healthy preadolescents and healthy adults as well as in preserved and degrading osteoarthritic cartilage from the same osteoarthritic joint by quantitative PCR. Subsequently, we exposed human articular chondrocytes to WNT, BMP, IL-1β, Indian hedgehog, parathyroid hormone-related peptide, mechanical loading, different medium tonicities or distinct oxygen levels and investigated GREM1, FRZB and DKK1 expression levels using a time-course analysis.
resultsGREM1, FRZB and DKK1 mRNA expression were strongly decreased in osteoarthritis. Moreover, this downregulation is stronger in degrading cartilage compared with macroscopically preserved cartilage from the same osteoarthritic joint. WNT, BMP, IL-1β signaling and mechanical loading regulated GREM1, FRZB and DKK1 mRNA levels. Indian hedgehog, parathyroid hormone-related peptide and tonicity influenced the mRNA levels of at least one antagonist, while oxygen levels did not demonstrate any statistically significant effect. Interestingly, BMP and WNT signaling upregulated the expression of each other's antagonists.
conclusionsTogether, the current study demonstrates an inverse correlation between osteoarthritis and GREM1, FRZB and DKK1 gene expression in cartilage and provides insight into the underlying transcriptional regulation. Furthermore, we show that BMP and WNT signaling are linked in a negative feedback loop, which might prove essential in articular cartilage homeostasis by balancing BMP and WNT activity.
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