Extracellular matrix formation by chondrocytes in monolayer culture.

Dessau, Waltraud; Vertel, Barbara M.; Mark, Helga von der; Mark, K von der

doi:10.1083/jcb.90.1.78

Cited by 58 publications

(30 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In culture, chondrocytes synthesize type II collagen (Muller et al, 1977) and accumulate it in the extracellular matrix in the form of short intracellular strands, probably when chondroitin sulphate proteoglycans have been already depostied (Dessau et al, 1981). We (Capasso et al, 1982).…”

Section: Introductionmentioning

confidence: 99%

The low molecular weight collagen synthesized by chick tibial chondrocytes is deposited in the extracellular matrix both in culture and in vivo.

Capasso¹,

Quarto²,

Descalzi-Cancedda³

et al. 1984

The EMBO Journal

View full text Add to dashboard Cite

*To whom reprint requests should be sent Communicated by A. Vaheri The low mol. wt. collagen (64 K) synthesized by chick embryo chondrocytes in culture is deposited in the extracellular matrix; its deposition is strictly dependent upon a correct hydroxylation. In vivo the 64 K collagen has been isolated from the cartilage of tibiae obtained from 17-day-old chick embryos. The turnover of this collagen in the extracellular matrix is very rapid: within a few hours it is matured into a 30-K fragment released in the medium. Also this maturation is dependent upon a correct hydroxylation of the molecule. The underhydroxylated form, synthesized in the absence of ascorbic acid or in the presence of ca-a' dipyridyl, is not deposited in the extracellular matrix and is directly secreted as 64 K collagen in the culture medium. Key words: low molecular weight collagen/chick embryo chondrocytes/extracellular matrix/collagen maturation A still unanswered question is whether the 64 K collagen is deposited in the extracellular matrix. Schmid and Conrad (1982a) have reported that this molecule was not present in the extracellular collagen pool recovered from the matrix of chondrocyte monolayers, but was contained in the extracellular collagen pool recovered in the culture medium.

show abstract

Section: Introductionmentioning

confidence: 99%

The low molecular weight collagen synthesized by chick tibial chondrocytes is deposited in the extracellular matrix both in culture and in vivo.

Capasso¹,

Quarto²,

Descalzi-Cancedda³

et al. 1984

The EMBO Journal

View full text Add to dashboard Cite

show abstract

“…Another common feature of all chondrocytes is the interdependence of cell shape and differentiation status (17)(18)(19)(20). Chondrogenesis is characterized by drastic changes in cell shape from a fibroblastoid to a round or polygonal morphology (21).…”

mentioning

confidence: 99%

RhoA/ROCK Signaling Regulates Sox9 Expression and Actin Organization during Chondrogenesis

Woods¹,

Wang²,

Beier

2005

Journal of Biological Chemistry

265

277

View full text Add to dashboard Cite

Endochondral ossification is initiated by the differentiation of mesenchymal precursor cells to chondrocytes (chondrogenesis). This process is characterized by a strong interdependence of cell shape, cytoskeletal organization, and the onset of chondrogenic gene expression, but the molecular mechanisms mediating these interactions are not known. Here we investigated the role of the RhoA/ROCK pathway, a well characterized regulator of cytoskeletal organization, in chondrogenesis. We show that pharmacological inhibition of ROCK signaling by Y27632 resulted in increased glycosaminoglycan synthesis and elevated expression of the chondrogenic transcription factor Sox9, whereas overexpression of RhoA in the chondrogenic cell line ATDC5 had the opposite effects. Suppression of Sox9 expression by ROCK signaling was achieved through repression of Sox9 promoter activity. These molecular changes were accompanied by reorganization of the actin cytoskeleton, where RhoA/ROCK signaling suppressed cortical actin organization, a hallmark of differentiated chondrocytes. This led us to analyze the regulation of Sox9 expression by drugs affecting cytoskeletal dynamics. Both inhibition of actin polymerization by cytochalasin D and stabilization of existing actin filaments by jasplakinolide resulted in increased Sox9 mRNA levels, whereas inhibition of microtubule polymerization by colchicine completely blocked Sox9 expression. In conclusion, our data suggest that RhoA/ROCK signaling suppresses chondrogenesis through the control of Sox9 expression and actin organization.

show abstract

“…matrix metalloproteinase (MMP) and aggrecanase families (8,9), and subsequent replacement with new protein synthesized by chondrocytes (10,11), resulting in a balance between anabolism and catabolism. With the onset of OA, the balance shifts toward degradation.…”

mentioning

confidence: 99%

Global analyses of gene expression in early experimental osteoarthritis

Appleton¹,

Pitelka²,

Henry³

et al. 2007

Arthritis & Rheumatism

222

224

View full text Add to dashboard Cite

Objective. To analyze genome-wide changes in chondrocyte gene expression in a surgically induced model of early osteoarthritis (OA) in rats, to assess the similarity of this model to human OA, and to identify genes and mechanisms leading to OA pathogenesis.Methods. OA was surgically induced in 5 rats by anterior cruciate ligament transection and partial medial meniscectomy. Sham surgery was performed in 5 additional animals, which were used as controls. Both groups underwent 4 weeks of forced mobilization, 3 times per week. RNA was extracted directly from articular chondrocytes in the OA (operated), contralateral, and sham-operated knees. Affymetrix GeneChip expression arrays were used to assess genome-wide changes in gene expression. Expression patterns of selected dysregulated genes, including Col2a1, Mmp13, Adamts5, Ctsc, Ptges, and Cxcr4, were validated by real-time polymerase chain reaction, immunofluorescence, or immunohistochemistry 2, 4, and 8 weeks after surgery.Results. After normalization, comparison of OA and sham-operated samples showed 1,619 differentially expressed probe sets with changes in their levels of expression >1.5-fold, 722 with changes >2-fold, 135 with changes >4-fold, and 20 with changes of 8-fold. Dysregulated genes known to be involved in human OA included Mmp13, Adamts5, and Ptgs2, among others. Several dysregulated genes (e.g., Reln, Phex, and Ltbp2) had been identified in our earlier microarray study of hypertrophic chondrocyte differentiation. Other genes involved in cytokine and chemokine signaling, including Cxcr4 and Ccl2, were identified. Changes in gene expression were also observed in the contralateral knee, validating the sham operation as the appropriate control.Conclusion. Our results demonstrate that the animal model mimics gene expression changes seen in human OA, supporting the relevance of newly identified genes and pathways to early human OA. We propose new avenues for OA pathogenesis research and potential targets for novel OA treatments, including cathepsins and cytokine, chemokine, and growth factor signaling pathways, in addition to factors controlling the progression of chondrocyte differentiation.

show abstract

Extracellular matrix formation by chondrocytes in monolayer culture.

Cited by 58 publications

References 34 publications

The low molecular weight collagen synthesized by chick tibial chondrocytes is deposited in the extracellular matrix both in culture and in vivo.

The low molecular weight collagen synthesized by chick tibial chondrocytes is deposited in the extracellular matrix both in culture and in vivo.

RhoA/ROCK Signaling Regulates Sox9 Expression and Actin Organization during Chondrogenesis

Global analyses of gene expression in early experimental osteoarthritis

Contact Info

Product

Resources

About