CCN3-mediated promotion of sulfated proteoglycan synthesis in rat chondrocytes from developing joint heads

Janune, Danilo; Kubota, Satoshi; Lazar, Noureddine; Perbal, Bernard; Iida, Seiji; Takigawa, Masaharu

doi:10.1007/s12079-011-0135-1

Cited by 8 publications

(11 citation statements)

References 27 publications

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“…The ECM of the articular cartilage in Nov del3 −/− male mice was also significantly different at 6 months, with decreased levels of proteoglycans and increased collagen fibre thickness compared to age and sex-matched littermates. Consistent with this, NOV has been reported to promote sulphated proteoglycan synthesis in chondrocytes isolated from developing rat epiphysis 24 . It would be of interest to determine whether ECM proteins that regulate collagen fibril size and diameter, such as decorin and collagen IX are altered in the Nov del3 −/−mice.…”

Section: Discussionsupporting

confidence: 65%

Targeted mutation of NOV/CCN3 in mice disrupts joint homeostasis and causes osteoarthritis-like disease

Roddy

Boulter

2015

Osteoarthritis and Cartilage

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SummaryObjectiveThe matricellular protein NOV/CCN3, is implicated in osteoarthritis (OA) and targeted mutation of NOV in mice (Novdel3) leads to joint abnormalities. This investigation tested whether NOV is required for joint homeostasis and if its disruption causes joint degeneration.MethodNOV expression in the adult mouse joint was characterized by immunohistochemistry. A detailed comparison of the joints of Novdel3−/− and Novdel3+/+ (wild-type) males and females at 2, 6 and 12 months of age was determined by X-ray, histology and immunohistochemistry.ResultsNOV protein was found in specific cells in articular cartilage, meniscus, synovium and ligament attachment sites in adult knees. Novdel3−/− males exhibited severe OA-like pathology at 12 months (OARSI score 5.0 ± 0.5, P < 0.001), affecting all tissues of the joint: erosion of the articular cartilage, meniscal enlargement, osteophytic outgrowths, ligament degeneration and expansion of fibrocartilage. Subchondral sclerosis and changes in extracellular matrix composition consistent with OA, were also seen. The density of articular cartilage cells in Novdel3+/+ knee joints is maintained at a constant level from 2 to 12 months of age whereas this is not the case in Novdel3−/− mice. Compared with age and sex-matched Novdel3+/+ mice, a significant increase in articular cartilage density was seen in Novdel3−/− males at 2 months, whereas a significant decrease was seen at 6 and 12 months in both Novdel3−/− males and females.ConclusionNOV is required for the maintenance of articular cartilage and for joint homeostasis, with disruption of NOV in ageing Novdel3−/− male mice causing OA-like disease.

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Section: Discussionsupporting

confidence: 65%

Targeted mutation of NOV/CCN3 in mice disrupts joint homeostasis and causes osteoarthritis-like disease

Roddy

Boulter

2015

Osteoarthritis and Cartilage

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“…Interestingly, application of MIA to articular cartilage in vivo results in immediate expenditure of CCN3 in articular cartilage and production of CCN3 in clustering chondrocytes, suggesting its role in cartilage protection (Janune et al 2017). CCN3 is shown to maintain the differentiated phenotype of articular chondrocytes, repressing their proliferation to save energy consumption (Janune et al 2011). Therefore, this metabolic regulation of CCN3 may be of critical significance in the maintenance of articular cartilage, although its precise molecular mechanism is still unclear.…”

Section: Discussionmentioning

confidence: 99%

Metabolic regulation of the CCN family genes by glycolysis in chondrocytes

Akashi

Nishida

El-Seoudi

et al. 2017

J. Cell Commun. Signal.

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The CCN family consists of 6 genes in the mammalian genome and produces multifunctional proteins involved in a variety of biological processes. Recent reports indicate the profound roles of CCN2 in energy metabolism in chondrocytes, and Ccn2 deficiency is known to alter the expression of 2 other family members including Ccn3. However, almost nothing is known concerning the regulation of the CCN family genes by energy metabolism. In order to gain insight into this critical issue, we initially and comprehensively evaluated the effect of inhibition of glycolysis on the expression of all of the CCN family genes in chondrocytic cells. Upon the inhibition of a glycolytic enzyme, repression of CCN2 expression was observed, whereas CCN3 expression was conversely induced. Similar repression of CCN2 was conferred by the inhibition of aerobic ATP production, which, however, did not induce CCN3 expression. In contrast, glucose starvation significantly enhanced the expression of CCN3 in those cells. The results of a reporter gene assay using a molecular construct containing a CCN3 proximal promoter revealed a dose-dependent induction of the CCN3 promoter activity by the glycolytic inhibitor in chondrocytic cells. These results unveiled a critical role of glycolytic activity in the regulation of CCN2 and CCN3, which activity mediated the mutual regulation of these 2 major CCN family members in chondrocytes.

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“…OA, a major clinical problem among the ageing population, is characterized by articular cartilage degeneration and synovial inflammation. CCN3 was highly expressed in articular chondrocytes in the normal rat articular cartilage [ 17 ], but it has an apparent decline in a monoiodoacetic acid- (MIA-) induced osteoarthritic model [ 56 ]. Consistently, another research also confirmed that the CCN3 expression was reduced in the cartilage tissue of OA patients and OA rat models [ 57 ].…”

Section: The Roles Of Ccn3 Protein In Immune-related Diseasesmentioning

confidence: 99%

“…In human early embryonic development, CCN3 is widely expressed in the derivative of all three germ layers [ 15 ]. In adult mammals, high CCN3 expression is observed in endotheliocytes, smooth muscle cells, fibroblasts, and chondrocytes [ 14 , 16 , 17 ]. Besides, Dombrowski et al first discovered that CCN3 can be produced by regulatory T cells (Treg) [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

The Emerging Roles of CCN3 Protein in Immune-Related Diseases

Peng

Wei

Shao

et al. 2021

Mediators of Inflammation

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The CCN proteins are a family of extracellular matrix- (ECM-) associated proteins which currently consist of six secreted proteins (CCN1-6). CCN3 protein, also known as nephroblastoma overexpressed protein (NOV), is a member of the CCN family with multiple biological functions, implicated in major cellular processes such as cell growth, migration, and differentiation. Recently, CCN3 has emerged as a critical regulator in a variety of diseases, including immune-related diseases, including rheumatology arthritis, osteoarthritis, and systemic sclerosis. In this review, we will briefly introduce the structure and function of the CCN3 protein and summarize the roles of CCN3 in immune-related diseases, which is essential to understand the functions of the CCN3 in immune-related diseases.

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CCN3-mediated promotion of sulfated proteoglycan synthesis in rat chondrocytes from developing joint heads

Cited by 8 publications

References 27 publications

Targeted mutation of NOV/CCN3 in mice disrupts joint homeostasis and causes osteoarthritis-like disease

Targeted mutation of NOV/CCN3 in mice disrupts joint homeostasis and causes osteoarthritis-like disease

Metabolic regulation of the CCN family genes by glycolysis in chondrocytes

The Emerging Roles of CCN3 Protein in Immune-Related Diseases

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