Редактирование: CCN2

CCN family member 2 precursor (Cellular communication network factor 2) (Connective tissue growth factor) (Hypertrophic chondrocyte-specific protein 24) (Insulin-like growth factor-binding protein 8) (IBP-8) (IGF-binding protein 8) (IGFBP-8) [CTGF] [HCS24] [IGFBP8]

==Publications==

{{medline-entry
|title=[[CCN2]] induces cellular senescence in fibroblasts.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27752926
|abstract=The expression of Ccn2 (CTGF) has been linked to fibrosis in many tissues and pathologies, although its activities in fibroblastic cells and precise mechanism of action in fibrogenesis are still controversial. Here, we showed that [[CCN2]] can induce cellular senescence in fibroblasts both in vitro and in vivo, whereupon senescent cells express an anti-fibrotic "senescence-associated secretory phenotype" (SASP) that includes upregulation of matrix metalloproteinases and downregulation of collagen. Mechanistically, [[CCN2]] induces fibroblast senescence through integrin α β -mediated accumulation of reactive oxygen species, leading to activation of p53 and induction of p16 . In cutaneous wound healing, Ccn2 expression is highly elevated only during the initial inflammatory phase and quickly declines thereafter to a low level during the proliferation and maturation phases of healing when myofibroblasts play a major role. Consistent with this expression kinetics, knockdown of Ccn2 has little effect on the rate of wound closure, formation of senescent cells, or collagen content of the wounds. However, application of purified [[CCN2]] protein on cutaneous wounds leads to induction of senescent cells, expression of SASP, and reduction of collagen content. These results show that [[CCN2]] can induce cellular senescence in fibroblasts and is capable of exerting an anti-fibrotic effect in a context-dependent manner.

|keywords=* CCN1/CYR61
* CCN2/CTGF
* Cellular senescence
* Integrins
* Wound healing
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5362572
}}
{{medline-entry
|title=Generation and Analysis of Cartilage-Specific [[CCN2]] Overexpression in Transgenic Mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27734391
|abstract=Recent progress in gene-editing technology has provided a strong impact for improved our understanding of molecular functions in living organisms. Here we describe our method to generate transgene-overexpressing mouse models, which method involves the use of tissue-specific promoters for analyzing a certain molecule (s) in special tissues. The protocol described in this chapter uses the Col2a1 promoter-enhancer, which is known for driving specific and strong transgene expression in cartilage and is based on several of our studies showing a positive role of the connective tissue growth factor ([[CCN2]]) in cartilage-bone development and maintenance of articular cartilage. These mice show strongly accelerated endochondral ossification resulting in enhanced bone elongation, as well as resistance to age-related articular degeneration. This protocol also describes how to analyze the molecular mechanisms of these phenomena by use of chondrocytes isolated from [[CCN2]]-overexpressing cartilage.
|mesh-terms=* Animals
* Cartilage, Articular
* Chondrocytes
* Chondrogenesis
* Connective Tissue Growth Factor
* Gene Expression
* Gene Order
* Genes, Reporter
* Genetic Vectors
* Genotype
* Mice
* Mice, Transgenic
* Organ Specificity
* Promoter Regions, Genetic
* beta-Galactosidase
|keywords=* Aging
* Cartilage
* Col2a1 promoter-enhancer
* Development
* Endochondral ossification
* Histochemistry
* IGF
* LacZ staining
* Skeletal preparation
* Transgenic
|full-text-url=https://sci-hub.do/10.1007/978-1-4939-6430-7_32
}}
{{medline-entry
|title=CCN family member 2/connective tissue growth factor ([[CCN2]]/C[[TG]]F) has anti-aging effects that protect articular cartilage from age-related degenerative changes.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23951098
|abstract=To examine the role of connective tissue growth factor [[CCN2]]/C[[TG]]F ([[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. 
|mesh-terms=* Aging
* Animals
* Cartilage, Articular
* Cell Proliferation
* Chondrocytes
* Chondrogenesis
* Collagen Type II
* Connective Tissue Growth Factor
* Disease Models, Animal
* Female
* Gene Expression
* Gene Expression Regulation
* Knee Joint
* Male
* Matrix Metalloproteinase 13
* Mice
* Mice, Transgenic
* Osteoarthritis
* Proteoglycans
* Radiography
* Stress, Mechanical

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3741357
}}
{{medline-entry
|title=Impaired intervertebral disc development and premature disc degeneration in mice with notochord-specific deletion of [[CCN2]].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23839921
|abstract=Currently, our ability to treat intervertebral disc ([[IVD]]) degeneration is hampered by an incomplete understanding of disc development and aging. The specific function of matricellular proteins, including [[CCN2]], during these processes remains an enigma. The aim of this study was to determine the tissue-specific localization of CCN proteins and to characterize their role in [[IVD]] tissues during embryonic development and age-related degeneration by using a mouse model of notochord-specific [[CCN2]] deletion. Expression of CCN proteins was assessed in [[IVD]] tissues from wild-type mice beginning on embryonic day 15.5 to 17 months of age. Given the enrichment of [[CCN2]] in notochord-derived tissues, we generated notochord-specific [[CCN2]]-null mice to assess the impact on the [[IVD]] structure and extracellular matrix composition. Using a combination of histologic evaluation and magnetic resonance imaging (MRI), [[IVD]] health was assessed. Loss of the [[CCN2]] gene in notochord-derived cells disrupted the formation of [[IVD]]s in embryonic and newborn mice, resulting in decreased levels of aggrecan and type II collagen and concomitantly increased levels of type I collagen within the nucleus pulposus. [[CCN2]]-knockout mice also had altered expression of [[CCN1]] (Cyr61) and [[CCN3]] (Nov). Mirroring its role during early development, notochord-specific [[CCN2]] deletion accelerated age-associated degeneration of [[IVD]]s. Using a notochord-specific gene targeting strategy, this study demonstrates that [[CCN2]] expression by nucleus pulposus cells is essential to the regulation of [[IVD]] development and age-associated tissue maintenance. The ability of [[CCN2]] to regulate the composition of the intervertebral disc suggests that it may represent an intriguing clinical target for the treatment of disc degeneration.
|mesh-terms=* Aggrecans
* Aging
* Animals
* Collagen Type I
* Collagen Type II
* Connective Tissue Growth Factor
* Disease Models, Animal
* Embryonic Development
* Female
* Intervertebral Disc
* Intervertebral Disc Degeneration
* Magnetic Resonance Imaging
* Male
* Mice
* Mice, Inbred C57BL
* Mice, Knockout
* Notochord

|full-text-url=https://sci-hub.do/10.1002/art.38075
}}
{{medline-entry
|title=Novel chondrogenic and chondroprotective effects of the natural compound harmine.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23116713
|abstract=A significant number of natural compounds have been shown to regulate the behavior of the cells, in collaboration with cellular proteins. [[CCN2]]/connective tissue growth factor (CTGF) has been reported to have essential roles in cartilage development, chondrocyte proliferation and differentiation as well as regulation of the extracellular matrix metabolism. Previous studies demonstrated the capability of [[CCN2]] to regenerate surgical defects in articular cartilage of rat knee. Also, transgenic mice over-expressing cartilage-specific [[CCN2]] were shown to be more resistant to aging-related cartilage degradation. We hypothesized that small molecules that induce [[CCN2]] in chondrocytes could be novel candidates to increase the resistance to aging-related cartilage degradation, or even to correct cartilage degenerative changes incurred in OA. Therefore, this study screened a compound library and identified the β-carboline alkaloid harmine as a novel inducer of [[CCN2]] in human chondrocytic HCS-2/8 cells and osteoarthritic articular chondrocytes. Harmine increased the expression of the cartilage markers aggrecan and COL2α1, as well as that of the master regulator of chondrogenesis, SOX-9. Moreover, harmine notably induced chondrogenesis of prechondrocytic ATDC5 cells in micromass cultures. The chondroprotective effect of harmine was investigated under inflammatory condition by stimulation with TNFα, and harmine was shown to ameliorate TNFα-induced decrease in expression of [[CCN2]] and cartilage markers. These findings uncover novel chondrogenic effects of harmine and indicate harmine as a potential drug for prevention and/or repair of cartilage degradation.
|mesh-terms=* Aggrecans
* Aging
* Anti-Inflammatory Agents, Non-Steroidal
* Biomarkers
* Cartilage, Articular
* Cell Differentiation
* Cells, Cultured
* Chondrocytes
* Chondrogenesis
* Collagen Type II
* Connective Tissue Growth Factor
* Extracellular Matrix
* Gene Expression
* Harmine
* Humans
* Osteoarthritis
* Protective Agents
* SOX9 Transcription Factor
* Small Molecule Libraries
* Tumor Necrosis Factor-alpha

|full-text-url=https://sci-hub.do/10.1016/j.biochi.2012.10.016
}}