ArticleBone2009
CCN family 2/connective tissue growth factor (CCN2/CTGF) regulates the expression of Vegf through Hif-1alpha expression in a chondrocytic cell line, HCS-2/8, under hypoxic condition.
Article in Bone, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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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.
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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
25 citing papers in PubMed, 44 citations in OpenAlex.
- Current research on the role of HIF in intervertebral disc degeneration.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2026Review
- Crosstalk between bone and vasculature within bone.Fundamental research · 2026Review
- Rescue of murine hind limb ischemia via angiogenesis and lymphangiogenesis promoted by cellular communication network factor 2.Scientific reports · 2023Article
- CTGF as a multifunctional molecule for cartilage and a potential drug for osteoarthritis.Frontiers in endocrinology · 2022Review
- CCN proteins in the musculoskeletal system: current understanding and challenges in physiology and pathology.Journal of cell communication and signaling · 2021Review
- Aging Disrupts Muscle Stem Cell Function by Impairing Matricellular WISP1 Secretion from Fibro-Adipogenic Progenitors.Cell stem cell · 2019Article
- In Vitro Identification of New Transcriptomic and miRNomic Profiles Associated with Pulmonary Fibrosis Induced by High Doses Everolimus: Looking for New Pathogenetic Markers and Therapeutic Targets.International journal of molecular sciences · 2018Article
- Connective tissue growth factor-specific monoclonal antibody inhibits growth of malignant mesothelioma in an orthotopic mouse model.Oncotarget · 2018Article
- In vivo expression and regulation of genes associated with vascularization during early response of sutures to tensile force.Journal of bone and mineral metabolism · 2017Article
- Microrna-199a-5p Functions as a Tumor Suppressor via Suppressing Connective Tissue Growth Factor (CTGF) in Follicular Thyroid Carcinoma.Medical science monitor : international medical journal of experimental and clinical research · 2016Article
- Fibrosis and hypoxia-inducible factor-1α-dependent tumors of the soft tissue on loss of von Hippel-Lindau in mesenchymal progenitors.The American journal of pathology · 2015Article
- Physical interaction of CCN2 with diverse growth factors involved in chondrocyte differentiation during endochondral ossification.Journal of cell communication and signaling · 2015Article
- CCN family protein 2 (CCN2) promotes the early differentiation, but inhibits the terminal differentiation of skeletal myoblasts.Journal of biochemistry · 2015Article
- Article
- Molecular regulation of CCN2 in the intervertebral disc: lessons learned from other connective tissues.Matrix biology : journal of the International Society for Matrix Biology · 2013Review
- Hypoxia-inducible factor (HIF)-1α and CCN2 form a regulatory circuit in hypoxic nucleus pulposus cells: CCN2 suppresses HIF-1α level and transcriptional activity.The Journal of biological chemistry · 2013Article
- Enhanced production of CTGF and IL-11 from highly metastatic hepatoma cells under hypoxic conditions: an implication of hepatocellular carcinoma metastasis to bone.Journal of cancer research and clinical oncology · 2013Article
- CTGF drives autophagy, glycolysis and senescence in cancer-associated fibroblasts via HIF1 activation, metabolically promoting tumor growth.Cell cycle (Georgetown, Tex.) · 2012Article
- Roles for CCN2 in normal physiological processes.Cellular and molecular life sciences : CMLS · 2011Review
- CTGF is overexpressed in papillary thyroid carcinoma and promotes the growth of papillary thyroid cancer cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2011Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Vascular endothelial growth factor (VEGF) is essential for establishing vascularization and regulating chondrocyte development and survival. We have demonstrated that VEGF regulates the expression of CCN2/connective tissue growth factor (CCN2/CTGF) an essential mediator of cartilage development and angiogenesis, suggesting that CCN2 functions in down-stream of VEGF, and that VEGF function is mediated in part by CCN2. On the other hand, the phenotype of Ccn2 mutant growth plates, which exhibit decreased expression of VEGF in the hypertrophic zone, indicates that Vegf expression is dependent on Ccn2 expression as well. Therefore, we investigated the molecular mechanisms underlying the induction of VEGF by CCN2 using a human chondrocytic cell line, HCS-2/8. Hypoxic stimulation (5% O(2)) of HCS-2/8 cells increased VEGF mRNA levels by approximately 8 fold within 6 h as compared with the cells cultured under normoxia. In addition, VEGF expression was further up-regulated under hypoxia in HCS-2/8 cells transfected with a Ccn2 expression plasmid. Hypoxia-inducible factor (HIF)-1alpha mRNA and protein levels were increased by stimulation with recombinant CCN2 (rCCN2). Furthermore, the activity of a VEGF promoter that contained a HIF-1 binding site was increased in HCS-2/8, when the cells were stimulated by rCCN2. These results suggest that CCN2 regulates the expression of VEGF at a transcriptional level by promoting HIF-1alpha activity. In fact, HIF-1alpha was detected in the nuclei of proliferative and pre-hypertrophic chondrocytes of wild-type mice, whereas it was not detected in Ccn2 mutant chondrocytes in vivo. This activation cascade from CCN2 to VEGF may therefore play a critical role in chondrocyte development and survival.
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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.