ArticleAnnals of the rheumatic diseases2018
Connective tissue growth factor contributes to joint homeostasis and osteoarthritis severity by controlling the matrix sequestration and activation of latent TGFβ.
Article in Annals of the rheumatic diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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54 citing papers in PubMed, 93 citations in OpenAlex.
- Recent advances in understanding molecular and clinical heterogeneity in osteoarthritis: one disease or several?Osteoarthritis imaging · 2026Article
- Abnormal Stress Reduced miR-330 Supplementation Alleviates Osteoarthritis Progression by Suppressing Osteochondral Catabolism.Aging cell · 2026Article
- Role of external forces in the mechanobiology of stem and differentiated chondrogenic cells embedded in a tissue-engineered construct for cartilage repair.Journal of biomedical science · 2026Review
- Heparan sulfate as a central modulator of growth factor dynamics in tissue regeneration.APL bioengineering · 2025Article
- Structure, Mechanics, and Mechanobiology of Fibrocartilage Pericellular Matrix Mediated by Type V Collagen.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A Self-Assembling LYTAC Mediates CTGF Degradation and Remodels Inflammatory Tumor Microenvironment for Triple-Negative Breast Cancer Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Rethinking Osteoarthritis Management: Synergistic Effects of Chronoexercise, Circadian Rhythm, and Chondroprotective Agents.Biomedicines · 2025Article
- Cell mediated reactions create TGF-β delivery limitations in engineered cartilage.Acta biomaterialia · 2024Article
- Review
- Human umbilical cord mesenchymal stem cells on treating osteoarthritis in a rabbit model: Injection strategies.Heliyon · 2024Article
- Morphological and histological features of thicker cartilage at the posterior medial femoral condyle in advanced knee osteoarthritis.Osteoarthritis and cartilage open · 2024Article
- Growth factors that drive aggrecan synthesis in healthy articular cartilage. Role for transforming growth factor-β?Osteoarthritis and cartilage open · 2024Review
- Osteoarthritis: Insights into Diagnosis, Pathophysiology, Therapeutic Avenues, and the Potential of Natural Extracts.Current issues in molecular biology · 2024Review
- Piezo1 expression in chondrocytes controls endochondral ossification and osteoarthritis development.Bone research · 2024Article
- The roles and regulatory mechanisms of TGF-β and BMP signaling in bone and cartilage development, homeostasis and disease.Cell research · 2024Review
- ER stress-induced YAP upregulation leads to chondrocyte phenotype loss in age-related osteoarthritis.Frontiers in pharmacology · 2024Article
- Meniscal fibrocartilage regeneration inspired by meniscal maturational and regenerative process.Science advances · 2023Article
- The Dual-Responsive Interaction of Particulated Hyaline Cartilage and Plasma Rich in Growth Factors (PRGF) in the Repair of Cartilage Defects: An In Vitro Study.International journal of molecular sciences · 2023Article
- Computational and experimental characterizations of the spatiotemporal activity and functional role of TGF-β in the synovial joint.Journal of biomechanics · 2023Article
- An Integrated View of Stressors as Causative Agents in OA Pathogenesis.Biomolecules · 2023Review
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
objectivesOne mechanism by which cartilage responds to mechanical load is by releasing heparin-bound growth factors from the pericellular matrix (PCM). By proteomic analysis of the PCM, we identified connective tissue growth factor (CTGF) and here investigate its function and mechanism of action.
methodsRecombinant CTGF (rCTGF) was used to stimulate human chondrocytes for microarray analysis. Endogenous CTGF was investigated by in vitro binding assays and confocal microscopy. Its release from cut cartilage (injury CM) was analysed by Western blot under reducing and non-reducing conditions. A postnatal, conditional Ctgf
resultsThe biological responses of rCTGF were TGFβ dependent. CTGF displaced latent TGFβ from cartilage and both were released on cartilage injury. CTGF and latent TGFβ migrated as a single high molecular weight band under non-reducing conditions, suggesting that they were in a covalent (disulfide) complex. This was confirmed by immunoprecipitation. Using Ctgf
conclusionsCTGF is a latent TGFβ binding protein that controls the matrix sequestration and activation of TGFβ in cartilage. Deletion of CTGF in vivo caused a paradoxical increase in Smad2 phosphorylation resulting in thicker cartilage that was protected from OA.
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