ArticlePloS one2013
CCN family member 2/connective tissue growth factor (CCN2/CTGF) has anti-aging effects that protect articular cartilage from age-related degenerative changes.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Meta-analysis Integrated With Multi-omics Data Analysis to Elucidate Pathogenic Mechanisms of Age-Related Knee Osteoarthritis in Mice.The journals of gerontology. Series A, Biological sciences and medical sciences · 2022Pooled it
- Single-Cell Transcriptomic Profiling Reveals Superficial Zone Chondrocytes as a Catabolic and Senescent Focus in Osteoarthritis Cartilage.Cartilage · 2026Article
- Single-cell RNA sequencing generates an atlas of normal tibia cartilage under mechanical loading conditions.Molecular and cellular biochemistry · 2025Article
- Skeletal progenitor LRP1 deficiency causes severe and persistent skeletal defects with Wnt pathway dysregulation.Bone research · 2025Article
- Extracellular vesicles from human urine-derived stem cells delay aging through the transfer of PLAU and TIMP1.Acta pharmaceutica Sinica. B · 2024Article
- Propolis as a Potential Therapeutic Agent to Counteract Age-Related Changes in Cartilage: An In Vivo Study.International journal of molecular sciences · 2023Article
- Treatment with CR500® improves algofunctional scores in patients with knee osteoarthritis: a post-market confirmatory interventional, single arm clinical investigation.BMC musculoskeletal disorders · 2023Article
- Fibroblast Growth Factors and Cellular Communication Network Factors: Intimate Interplay by the Founding Members in Cartilage.International journal of molecular sciences · 2022Review
- Molecular and Genetic Interactions between CCN2 and CCN3 behind Their Yin-Yang Collaboration.International journal of molecular sciences · 2022Review
- CTGF as a multifunctional molecule for cartilage and a potential drug for osteoarthritis.Frontiers in endocrinology · 2022Review
- Cellular communication network factor 3 in cartilage development and maintenance.Journal of cell communication and signaling · 2021Review
- CCN proteins in the musculoskeletal system: current understanding and challenges in physiology and pathology.Journal of cell communication and signaling · 2021Review
- Targeting CCN Proteins in Rheumatoid Arthritis and Osteoarthritis.International journal of molecular sciences · 2021Review
- Bipartite regulation of cellular communication network factor 2 and fibroblast growth factor 1 genes by fibroblast growth factor 1 through histone deacetylase 1 and fork head box protein A1.Journal of cell communication and signaling · 2021Article
- Histological Evaluation and Gene Expression Profiling of Autophagy-Related Genes for Cartilage of Young and Senescent Rats.International journal of molecular sciences · 2020Article
- Post-traumatic osteoarthritis development is not modified by postnatal chondrocyte deletion ofDisease models & mechanisms · 2020Article
- Connective Tissue Growth Factor: From Molecular Understandings to Drug Discovery.Frontiers in cell and developmental biology · 2020Review
- The pathogenic role of connective tissue growth factor in osteoarthritis.Bioscience reports · 2019Review
- Role of ADAMTS-12 in Protecting Against Inflammatory Arthritis in Mice By Interacting With and Inactivating Proinflammatory Connective Tissue Growth Factor.Arthritis & rheumatology (Hoboken, N.J.) · 2018Article
- Commensal Microbiota Enhance Both Osteoclast and Osteoblast Activities.Molecules (Basel, Switzerland) · 2018Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To examine the role of connective tissue growth factor CCN2/CTGF (CCN2) in the maintenance of the articular cartilaginous phenotype, we analyzed knee joints from aging transgenic mice (TG) overexpressing CCN2 driven by the Col2a1 promoter. Knee joints from 3-, 14-, 40-, and 60-day-old and 5-, 12-, 18-, 21-, and 24-month-old littermates were analyzed. Ccn2-LacZ transgene expression in articular cartilage was followed by X-gal staining until 5 months of age. Overexpression of CCN2 protein was confirmed through all ages in TG articular cartilage and in growth plates. Radiographic analysis of knee joints showed a narrowing joint space and other features of osteoarthritis in 50% of WT, but not in any of the TG mice. Transgenic articular cartilage showed enhanced toluidine blue and safranin-O staining as well as chondrocyte proliferation but reduced staining for type X and I collagen and MMP-13 as compared with those parameters for WT cartilage. Staining for aggrecan neoepitope, a marker of aggrecan degradation in WT articular cartilage, increased at 5 and 12 months, but disappeared at 24 months due to loss of cartilage; whereas it was reduced in TG articular cartilage after 12 months. Expression of cartilage genes and MMPs under cyclic tension stress (CTS) was measured by using primary cultures of chondrocytes obtained from wild-type (WT) rib cartilage and TG or WT epiphyseal cartilage. CTS applied to primary cultures of mock-transfected rib chondrocytes from WT cartilage and WT epiphyseal cartilage induced expression of Col1a1, ColXa1, Mmp-13, and Mmp-9 mRNAs; however, their levels were not affected in CCN2-overexpressing chondrocytes and TG epiphyseal cartilage. In conclusion, cartilage-specific overexpression of CCN2 during the developmental and growth periods reduced age-related changes in articular cartilage. Thus CCN2 may play a role as an anti-aging factor by stabilizing articular cartilage.
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