CTGF/Hcs24, a hypertrophic chondrocyte‐specific gene product, stimulates proliferation and differentiation, but not hypertrophy of cultured articular chondrocytes

Nishida, Takashi; Kubota, Satoshi; Nakanishi, Tohru; Kuboki, Takuo; Yosimichi, Gen; Kondo, Seiji; Takigawa, Masaharu

doi:10.1002/jcp.10113

Cited by 109 publications

(123 citation statements)

References 27 publications

Supporting

Mentioning

111

Contrasting

Order By: Relevance

“…Furthermore, the rCTGF/Hcs24 effectively stimulated the gene expression of collagen type X, a marker of chondrocyte hypertrophy, in RGC cells in overconfluent culture where the cells were in the prehypertrophic stage . Moreover, the rCTGF/Hcs24 stimulated ALPase activity, a marker of calcification, and indeed induced matrix calcification of RGC cells in culture (Nishida et al, 2002b). These results indicate that CTGF/Hcs24 directly promotes the proliferation and differentiation of growth cartilage cells toward endochondral ossification (Fig.…”

Section: Roles Of Ctgf/hcs24 In the Proliferation And Differentiationmentioning

confidence: 57%

“…Although the rCTGF/Hcs24 stimulated the gene expression of type II collagen and aggrecan core protein, which are markers of chondrocyte maturation, in both RGC and RAC cells, the gene expression of type X collagen, a marker of hypertrophic chondrocytes, was stimulated by rCTGF/Hcs24 only in RGC cells, but not in RAC cells (Nishida et al, 2002b). Oppositely, gene expression of tenascin-C, a marker of articular chondrocytes, was stimulated by rCTGF/Hcs24 in RAC cells, not in RGC cells (Nishida et al, 2002b). Moreover, rCTGF/Hcs24 effectively increased both ALPase activity and matrix calcification of RGC cells, but not those of RAC cells (Nishida et al, 2002b).…”

Section: Roles Of Ctgf/hcs24 In the Proliferation And Differentiationmentioning

confidence: 92%

“…Also, rCTGF/Hcs24 (20-50 ng/ml) increased DNA and proteoglycan syntheses in RAC cells (Nishida et al, 2002b). Although the rCTGF/Hcs24 stimulated the gene expression of type II collagen and aggrecan core protein, which are markers of chondrocyte maturation, in both RGC and RAC cells, the gene expression of type X collagen, a marker of hypertrophic chondrocytes, was stimulated by rCTGF/Hcs24 only in RGC cells, but not in RAC cells (Nishida et al, 2002b). Oppositely, gene expression of tenascin-C, a marker of articular chondrocytes, was stimulated by rCTGF/Hcs24 in RAC cells, not in RGC cells (Nishida et al, 2002b).…”

Section: Roles Of Ctgf/hcs24 In the Proliferation And Differentiationmentioning

confidence: 94%

“…Like RGC cells, rabbit articular cartilage (RAC) cells transfected with recombinant adenoviruses generating mRNA for CTGF/Hcs24 synthesized more proteoglycan than the control cells (Nishida et al, 2002b). Also, rCTGF/Hcs24 (20-50 ng/ml) increased DNA and proteoglycan syntheses in RAC cells (Nishida et al, 2002b).…”

Section: Roles Of Ctgf/hcs24 In the Proliferation And Differentiationmentioning

confidence: 99%

See 3 more Smart Citations

Role of CTGF/HCS24/ecogenin in skeletal growth control

Takigawa¹,

Nakanishi²,

Kubota³

et al. 2003

Journal Cellular Physiology

Self Cite

171

185

View full text Add to dashboard Cite

Connective tissue growth factor/hypertrophic chondrocyte-specific gene product 24 (CTGF/Hcs24) is a multifunctional growth factor for chondrocytes, osteoblasts, and vascular endothelial cells. CTGF/Hcs24 promotes the proliferation and maturation of growth cartilage cells and articular cartilage cells in culture and hypertrophy of growth cartilage cells in culture. The factor also stimulates the proliferation and differentiation of cultured osteoblastic cells. Moreover, CTGF/ Hcs24 promotes the adhesion, proliferation, and migration of vascular endothelial cells, as well as induces tube formation by the cells and strong angiogenesis in vivo. Because angiogenesis is critical for the replacement of cartilage with bone at the final stage of endochondral ossification and because gene expression of CTGF/ Hcs24 predominates in hypertrophic chondrocytes in the physiological state, a major physiological role for this factor should be the promotion of the entire process of endochondral ossification, with the factor acting on the above three types of cells as a paracrine factor. Thus, CTGF/Hcs24 should be called ''ecogenin: endochondral ossification genetic factor.'' In addition to hypertrophic chondrocytes, osteoblasts activated by various stimuli including wounding also express a significantly high level of CTGF/Hcs24. These findings in conjunction with in vitro findings about osteoblasts mentioned above suggest the involvement of CTGF/Hcs24 in intramembranous ossification and bone modeling/remodeling. Because angiogenesis is also critical for intramembranous ossification and bone remodeling, CTGF/ Hcs24 expressed in endothelial cells activated by various stimuli including wounding may also play important roles in direct bone formation. In conclusion, although the most important physiological role of CTGF/Hcs24 is ecogenin action, the factors also play important roles in skeletal growth and modeling/remodeling via its direct action on osteoblasts under both physiological and pathological conditions.

show abstract

Section: Roles Of Ctgf/hcs24 In the Proliferation And Differentiationmentioning

confidence: 57%

Section: Roles Of Ctgf/hcs24 In the Proliferation And Differentiationmentioning

confidence: 92%

Section: Roles Of Ctgf/hcs24 In the Proliferation And Differentiationmentioning

confidence: 94%

Section: Roles Of Ctgf/hcs24 In the Proliferation And Differentiationmentioning

confidence: 99%

See 2 more Smart Citations

Role of CTGF/HCS24/ecogenin in skeletal growth control

Takigawa¹,

Nakanishi²,

Kubota³

et al. 2003

Journal Cellular Physiology

Self Cite

171

185

View full text Add to dashboard Cite

show abstract

“…59 Similar results have been observed following transfer of human telomerase 60 and connective tissue growth factor/hypertrophic chondrocyte-specific gene product 24 (CTGF/Hcs24) into chondrocyte cultures. 61 From accumulating reports in the literature, it appears that the act of genetic modification either virally or nonvirally does not, in and of itself, adversely affect the physiology of the chondrocyte. Research emphasis has then shifted toward exploring the use of tissue engineering to deliver genetically modified chondrocytes.…”

Section: Chondrocytes As Targets For Gene Deliverymentioning

confidence: 99%

Gene-based approaches for the repair of articular cartilage

2004

View full text Add to dashboard Cite

WISP3‐dependent regulation of type II collagen and aggrecan production in chondrocytes

Sen¹,

Cheng²,

Goldring³

et al. 2004

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. WISP3 (Wnt-1-inducible secreted protein 3) is a member of the CCN (connective tissue growth factor, cysteine-rich 61, nephroblastoma overexpressed) family of connective tissue growth factors. WISP3 mutations have been linked to progressive pseudorheumatoid dysplasia (PPRD). The present study was conducted to investigate whether WISP3 is responsible for the expression of cartilage-specific molecules.Methods. WISP3 expression in human cartilage was assessed by immunostaining with anti-WISP3 antibody. The effect of WISP3 on chondrocyte-specific gene regulation was determined by transfecting human chondrocyte lines C-28/I2 and T/C-28a2 with a WISP3 expression vector. Alterations in WISP3-mediated messenger RNA and protein expression of cartilage-specific molecules were assessed by reverse transcriptasepolymerase chain reaction and immunoblotting.Results. Immunohistochemistry experiments demonstrated that WISP3 protein is expressed in the midzone chondrocytes of normal adult articular cartilage, in chondrocyte clusters of osteoarthritic cartilage, and in the zone of proliferating chondrocytes of fetal growth cartilage. Human chondrocyte lines C-28/I2 and T/C-28a2 transfected with a WISP3 expression vector produced increased amounts of the cartilage-specific matrix molecules type II collagen and aggrecan, in part via activation of the sex-determining region Y-type high mobility group box (SOX) family of transcription factors. In contrast, a mutant WISP3, previously found to be associated with PPRD, had impaired effects on cartilage-specific gene expression.Conclusion. Our experimental results suggest that WISP3 supports cartilage integrity by regulating the expression of type II collagen and aggrecan, and mutations linked with PPRD can compromise this function and produce cartilage loss.

show abstract

CTGF/Hcs24, a hypertrophic chondrocyte‐specific gene product, stimulates proliferation and differentiation, but not hypertrophy of cultured articular chondrocytes

Cited by 109 publications

References 27 publications

Role of CTGF/HCS24/ecogenin in skeletal growth control

Role of CTGF/HCS24/ecogenin in skeletal growth control

Gene-based approaches for the repair of articular cartilage

WISP3‐dependent regulation of type II collagen and aggrecan production in chondrocytes

Contact Info

Product

Resources

About