Analysis of cartilage maturation using micromass cultures of primary chondrocytes

Kameda, Takashi; Koike, Chika; Saitoh, Koichi; Kuroiwa, Atsushi; Iba, Hideo

doi:10.1046/j.1440-169x.2000.00508.x

Cited by 43 publications

(37 citation statements)

References 19 publications

(60 reference statements)

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“…The resulting increase in the corresponding proteins would further reduce the action of the IGFs, thus contributing to the loss of cartilage matrix in OA (64). Finally, a few studies have implicated BMP-6 as having a role in inducing the differentiation of chondrocytes in the growth plate (67,68).…”

Section: Discussionmentioning

confidence: 99%

Assessment of the gene expression profile of differentiated and dedifferentiated human fetal chondrocytes by microarray analysis

Stokes¹,

Liu²,

Coimbra³

et al. 2002

Arthritis & Rheumatism

152

106

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Objective. To study the changes in patterns of gene expression exhibited by human chondrocytes as they dedifferentiate into fibroblastic cells in culture in order to better understand the mechanisms that control this process and its relationship to the phenotypic changes that occur in chondrocytes during the development of osteoarthritis (OA).Methods. Human fetal epiphyseal chondrocytes (HFCs) were cultured either on poly-(2-hydroxyethyl methacrylate)-coated plates (differentiated HFC cultures) or in plastic tissue culture flasks as monolayers (dedifferentiated HFC cultures). Following 11 days of culture under either condition, poly(A؉) RNA was isolated from the two cell populations and subjected to a gene expression analysis using a microarray containing ϳ5,000 known human genes and ϳ3,000 expressed sequence tags (ESTs).Results. A >2-fold difference in the expression of 62 known genes and 6 ESTs was observed between the two cell types. The differences in expression of several of the genes detected by the microarray hybridization were confirmed by Northern analyses. Two transcription factor genes, TWIST and HIF-1␣, and a cellular adhesion protein gene, cadherin 11, were markedly regulated in response to differentiation and dedifferentiation. Expression of these genes was also detected in adult normal and OA cartilage and chondrocytes. Analysis of the gene expression profile of HFCs revealed a complex pattern of gene expression, including many genes not yet reported to be expressed by chondrocytes.Conclusion. Chondrocytes in monolayer become dedifferentiated, acquiring a fibroblast-like appearance and changing their pattern of gene expression from one of expression of chondrocyte-specific genes to one that resembles a fibroblastic or chondroprogenitor-like pattern. Changes in gene expression associated with the process of dedifferentiation of HFCs in vitro were observed in a wide variety of genes, including genes encoding extracellular matrix proteins, transcription factors, and growth factors. At least 3 of the genes that were regulated in response to dedifferentiation were also found to be expressed in adult normal and OA articular cartilage and chondrocytes.

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Section: Discussionmentioning

confidence: 99%

Assessment of the gene expression profile of differentiated and dedifferentiated human fetal chondrocytes by microarray analysis

Stokes¹,

Liu²,

Coimbra³

et al. 2002

Arthritis & Rheumatism

152

106

View full text Add to dashboard Cite

show abstract

“…HA is an important modulator or co-stimulator of signaling networks that have been implicated as positive regulators of chondrocyte maturation, including the BMP signal transduction pathway (Enomoto-Iwamoto et al, 1998;Volk et al, 1998;Grimsrud et al, 1999;Ito et al, 1999;Kameda et al, 2000;Volk et al, 2000;Bosky et al, 2002;Pogue and Lyons, 2006;Yoon et al, 2006). The upregulation of Has2 expression at the onset of hypertrophic maturation correlates with the upregulation of Bmp2 and Bmp6 and with the activation of the transcriptional mediators of BMP signaling, Smad1, 5 and 8 (Yoon et al, 2006).…”

Section: Development Developmentmentioning

confidence: 99%

Conditional inactivation ofHas2reveals a crucial role for hyaluronan in skeletal growth, patterning, chondrocyte maturation and joint formation in the developing limb

et al. 2009

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The glycosaminoglycan hyaluronan (HA) is a structural component of extracellular matrices and also interacts with cell surface receptors to directly influence cell behavior. To explore functions of HA in limb skeletal development, we conditionally inactivated the gene for HA synthase 2, Has2, in limb bud mesoderm using mice that harbor a floxed allele of Has2 and mice carrying a limb mesoderm-specific Prx1-Cre transgene. The skeletal elements of Has2-deficient limbs are severely shortened, indicating that HA is essential for normal longitudinal growth of all limb skeletal elements. Proximal phalanges are duplicated in Has2 mutant limbs indicating an involvement of HA in patterning specific portions of the digits. The growth plates of Has2-deficient skeletal elements are severely abnormal and disorganized, with a decrease in the deposition of aggrecan in the matrix and a disruption in normal columnar cellular relationships. Furthermore, there is a striking reduction in the number of hypertrophic chondrocytes and in the expression domains of markers of hypertrophic differentiation in the mutant growth plates, indicating that HA is necessary for the normal progression of chondrocyte maturation. In addition, secondary ossification centers do not form in the central regions of Has2 mutant growth plates owing to a failure of hypertrophic differentiation. In addition to skeletal defects, the formation of synovial joint cavities is defective in Has2-deficient limbs. Taken together, our results demonstrate that HA has a crucial role in skeletal growth, patterning, chondrocyte maturation and synovial joint formation in the developing limb.

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“…Another AP-1 family member, ATF-2, also contributes to endochondral ossification; chondrocyte proliferation is reduced in ATF-2-deficient mice, leading to dwarfism and skeletal deformities (17). Additionally, ectopic expression of Jun family members has been shown to perturb chondrocyte maturation (18).…”

mentioning

confidence: 99%

c-Jun/Activator Protein-1 Mediates Interleukin-1β-induced Dedifferentiation but Not Cyclooxygenase-2 Expression in Articular Chondrocytes

Hwang

Poo

et al. 2005

Journal of Biological Chemistry

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Analysis of cartilage maturation using micromass cultures of primary chondrocytes

Abstract: A micromass culture (MM-C)

Cited by 43 publications

References 19 publications

Assessment of the gene expression profile of differentiated and dedifferentiated human fetal chondrocytes by microarray analysis

Assessment of the gene expression profile of differentiated and dedifferentiated human fetal chondrocytes by microarray analysis

Conditional inactivation ofHas2reveals a crucial role for hyaluronan in skeletal growth, patterning, chondrocyte maturation and joint formation in the developing limb

c-Jun/Activator Protein-1 Mediates Interleukin-1β-induced Dedifferentiation but Not Cyclooxygenase-2 Expression in Articular Chondrocytes

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