The Chondrocyte: Biology and Clinical Application

Lin, Zhen; Willers, Craig; Xu, Jiake; Zheng, Minghao

doi:10.1089/ten.2006.12.1971

Cited by 181 publications

(106 citation statements)

References 134 publications

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“…The cells have been used as a model of normal and osteoarthritis chondrocytes in a number of studies (30,40,51). Of note, CCN2 originally was cloned as a hypertrophic chondrocyte-specific gene product 24 (Hcs24) from HCS-2/8 cells and was demonstrated to function as an endochondral ossification-promoting factor (50).…”

Section: Discussionmentioning

confidence: 99%

Novel Transcription Factor-Like Function of Human Matrix Metalloproteinase 3 Regulating the CTGF/CCN2 Gene

Eguchi¹,

Kubota²,

Kawata³

et al. 2008

Molecular and Cellular Biology

186

235

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Connective tissue growth factor (CTGF/CCN2) is a member of the CCN family of matricellular proteins and also has been designated Hcs24, FISP12, IGFBP8, IGFBP-rP2, ␤IG-M2, and ecogenin. The other CCN proteins include Cyr61/CCN1, NOV/CCN3, WISP1/CCN4, WISP2/CCN5, and WISP3/CCN6 (5, 26, 38, 39) as well, and they are structurally and functionally related glycoproteins involved in cell differentiation, proliferation, adhesion, migration, and the formation of the extracellular matrix. These matricellular functions of CCNs are involved in physiological processes such as wound healing, angiogenesis, morphogenesis, and embryogenesis as well as in pathological states including fibrotic disorders, cancer, and arthritis.Earlier we showed that CCN2 promotes endochondral ossification by acting on chondrocytes, osteoblasts, and endothelial cells (35,37,46). For example, CCN2 promotes physiological chondrocytic proliferation and extracellular matrix (ECM) formation. We also reported the regeneration of defects in articular cartilage in rat knee joints following treatment with recombinant CCN2 (36). Furthermore, ctgf-null mice were dead on delivery and were characterized by defective angiogenesis, the derangement of endochondral ossification, and dysmorphisms that occurred as a result of impaired chondrocyte proliferation and an abnormal ECM composition within the hypertrophic zone (24).Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that are involved in the remodeling and turnover of the ECM in physiological processes such as angiogenesis, wound healing, embryogenesis, and morphogenesis as well as in pathological states including cancers, myocardial infarction, fibrotic disorders, rheumatism, and osteoarthritis (33, 49). Cartilage is a connective tissue that is constructed by chondrocytes embedded within an ECM predominantly composed of collagens and proteoglycans. ECM remodeling is achieved by regulating the production and degradation of specific ECM components. MMPs, which comprise a large family of enzymes with differential abilities to degrade specific ECM components, play a vital role in this process. MMPs also cleave growth factors and their binding proteins, thereby activating or inhibiting specific signaling events (15). Of note, the expression and role of MMP3 have been investigated in the pathological status of articular cartilage, such as in osteoarthritis and rheumatism (1,52).Recent study has demonstrated the existence and functions of intracellular MMPs and tissue inhibitors of metalloproteinases (TIMPs). TIMP-1 accumulates in the cellular nuclei in association with the cell cycle (54). Alternative splicing and promoter usage generate an intracellular MMP11 isoform directly translated as an active MMP (31). MMP2 is found in the nuclei of cardiac myocytes and is capable of cleaving poly-(ADP-ribose) polymerase (PARP) in vitro (28). MMP3 also is detected in the nuclei of hepatocytes and is involved in apop-* Corresponding author. Mailing address:

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Section: Discussionmentioning

confidence: 99%

Novel Transcription Factor-Like Function of Human Matrix Metalloproteinase 3 Regulating the CTGF/CCN2 Gene

Eguchi¹,

Kubota²,

Kawata³

et al. 2008

Molecular and Cellular Biology

186

235

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“…1 Tissue engineering for cartilage reconstruction requires large numbers of cultured chondrocytes. In the case of autologous chondrocyte implantation (ACI), chondrocytes removed from patients are multiplied in vitro by monolayer culture to reach a minimum density of 10 million cells before they are implanted into the cartilage defect.…”

mentioning

confidence: 99%

“…[1][2][3][4][5]20 In this study, the gene expression profiles of normal and OA chondrocytes were compared. Surprisingly, little significant difference was observed between the two groups, suggesting that the in vitro biosynthetic profile of the chondrocyte is influenced more by the culture conditions, than the disease state of the donor cartilage.…”

mentioning

confidence: 99%

Gene expression profiles of human chondrocytes during passaged monolayer cultivation

Lin

Fitzgerald

et al. 2008

Journal Orthopaedic Research

Self Cite

178

148

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Chondrocyte phenotype has been shown to dedifferentiate during passaged monolayer cultivation. Hence, we have investigated the expression profile of 27 chondrocyte-associated genes from both osteoarthritic cartilage tissue and healthy passaged human articular chondrocytes by quantitative real-time PCR. Our results indicate that the gene expression levels of matrix proteins and proteases in chondrocytes from monolayer culture decrease compared with those from cartilage tissue, while monolayer cultured chondrocytes from normal and osteoarthritic cartilage exhibit similar gene expression patterns. However, chondrocytic gene expression profiles were differentially altered at various stages of passage. The expression of the matrix proteins aggrecan, type II collagen, and fibromodulin inversely correlated with increasing passage number, while fibronectin and link protein exhibited a marked increase with passage. The expression of matrix proteinases MMP-3/9/13 and ADAMTS-4/5 decreased with passage, whereas proteinase inhibitors TIMP-2/3 were elevated. The cytokine IL-1 also showed increased expression with monolayer chondrocyte culture, while IGF-1 expression levels were diminished. No significant changes in TGF-b, or the chondrogenic transcription factors Sox-9, c-fos, or c-jun were observed. Our data indicates that cultured chondrocytes undergo dedifferentiation during monolayer culture, although the gene expression level of transcription factors necessary for chondrogenesis remains unchanged. This data may prove important for the future development of more specific and efficacious cultivation techniques for human articular chondrocyte-based therapies. ß

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“…Strongly characteristic peaks of polyethylene glycol and polyethylenimine residues at approximately 3.65 ppm (peak B) and about 2.65 ppm (peaks D and E), respectively, were observed. 1 H-NMR spectroscopy further demonstrated that polyethylenimine was conjugated to the polyethylene glycol chains. The graft density of polyethylene glycol onto polyethylenimine was thus calculated to be four from the integral values of peak B and peaks D and E, using the known molecular weights of polyethylene glycol (2 kDa) and polyethylenimine (25 kDa).…”

Section: Thementioning

confidence: 98%

Plasmid-encapsulated polyethylene glycol-grafted polyethylenimine nanoparticles for gene delivery into rat mesenchymal stem cells

Chen

Zhang²,

He³

et al. 2011

IJN

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Background: Mesenchymal stem cell transplantation is a promising method in regenerative medicine. Gene-modified mesenchymal stem cells possess superior characteristics of specific tissue differentiation, resistance to apoptosis, and directional migration. Viral vectors have the disadvantages of potential immunogenicity, carcinogenicity, and complicated synthetic procedures. Polyethylene glycol-grafted polyethylenimine (PEG-PEI) holds promise in gene delivery because of easy preparation and potentially targeting modification. Methods: A PEG8k-PEI25k graft copolymer was synthesized. Agarose gel retardation assay and dynamic light scattering were used to determine the properties of the nanoparticles. MTT reduction, wound and healing, and differentiation assays were used to test the cytobiological characteristics of rat mesenchymal stem cells, fluorescence microscopy and flow cytometry were used to determine transfection efficiency, and atomic force microscopy was used to evaluate the interaction between PEG-PEI/plasmid nanoparticles and mesenchymal stem cells. Results: After incubation with the copolymer, the bionomics of mesenchymal stem cells showed no significant change. The mesenchymal stem cells still maintained high viability, resettled the wound area, and differentiated into adipocytes and osteoblasts. The PEG-PEI completely packed plasmid and condensed plasmid into stable nanoparticles of 100–150 nm diameter. After optimizing the N/P ratio, the PEG-PEI/plasmid microcapsules delivered plasmid into mesenchymal stem cells and obtained an optimum transfection efficiency of 15%–21%, which was higher than for cationic liposomes. Conclusion: These data indicate that PEG-PEI is a valid gene delivery agent and has better transfection efficiency than cationic liposomes in mesenchymal stem cells.

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The Chondrocyte: Biology and Clinical Application

Cited by 181 publications

References 134 publications

Novel Transcription Factor-Like Function of Human Matrix Metalloproteinase 3 Regulating the CTGF/CCN2 Gene

Novel Transcription Factor-Like Function of Human Matrix Metalloproteinase 3 Regulating the CTGF/CCN2 Gene

Gene expression profiles of human chondrocytes during passaged monolayer cultivation

Plasmid-encapsulated polyethylene glycol-grafted polyethylenimine nanoparticles for gene delivery into rat mesenchymal stem cells

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