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The nuclear factor of activated T cells (NFAT) transcription factor NFATp (NFATc2) is a repressor of chondrogenesis.

Ranger AM, Gerstenfeld LC, Wang J, Kon T, Bae H, Gravallese EM, Glimcher MJ, Glimcher LH - J. Exp. Med. (2000)

Bottom Line: Consistent with these data, NFATp expression is regulated in mesenchymal stem cells induced to differentiate along a chondrogenic pathway.Lack of NFATp in articular cartilage cells results in increased expression of cartilage markers, whereas overexpression of NFATp in cartilage cell lines extinguishes the cartilage phenotype.Thus, NFATp is a repressor of cartilage cell growth and differentiation and also has the properties of a tumor suppressor.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.

ABSTRACT
Nuclear factor of activated T cells (NFAT) transcription factors regulate gene expression in lymphocytes and control cardiac valve formation. Here, we report that NFATp regulates chondrogenesis in the adult animal. In mice lacking NFATp, resident cells in the extraarticular connective tissues spontaneously differentiate to cartilage. These cartilage cells progressively differentiate and the tissue undergoes endochondral ossification, recapitulating the development of endochondral bone. Proliferation of already existing articular cartilage cells also occurs in some older animals. At both sites, neoplastic changes in the cartilage cells occur. Consistent with these data, NFATp expression is regulated in mesenchymal stem cells induced to differentiate along a chondrogenic pathway. Lack of NFATp in articular cartilage cells results in increased expression of cartilage markers, whereas overexpression of NFATp in cartilage cell lines extinguishes the cartilage phenotype. Thus, NFATp is a repressor of cartilage cell growth and differentiation and also has the properties of a tumor suppressor.

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Absence of NFATp enhances, whereas overexpression of NFATp represses the cartilage phenotype. (A) RT-PCR analysis of mature cartilage gene expression in primary wt and NFATp−/− articular chondrocytes using types II and X collagen and HPRT primers. (B) Western blot analysis of S12 and EA control (Rep) and NFATp transfectants with anti-NFATp antibody. (C) RT-PCR analysis of mature cartilage gene expression of S12 and EA control and NFATp transfectants using type II collagen, type X collagen, CDMP-1, and actin primers (references 36–38).
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Figure 5: Absence of NFATp enhances, whereas overexpression of NFATp represses the cartilage phenotype. (A) RT-PCR analysis of mature cartilage gene expression in primary wt and NFATp−/− articular chondrocytes using types II and X collagen and HPRT primers. (B) Western blot analysis of S12 and EA control (Rep) and NFATp transfectants with anti-NFATp antibody. (C) RT-PCR analysis of mature cartilage gene expression of S12 and EA control and NFATp transfectants using type II collagen, type X collagen, CDMP-1, and actin primers (references 36–38).

Mentions: The uncontrolled proliferation of resident connective tissue cells and their differentiation to cartilage cells and the proliferation of existing articular cartilage cells, coupled with the regulated expression of NFATp in MSC cultures, suggested that NFATp represses the chondrogenic program. To further investigate this possibility, we took two approaches. First, we compared the levels of transcripts for type II and X collagen by semiquantitative RT-PCR in primary articular chondrocytes established from wt and NFATp−/− femoral heads. Fig. 5 A demonstrates that articular chondrocytes lacking NFATp have much higher (at least eightfold) levels of both type II and X collagen mRNA than wt articular cartilage cells.


The nuclear factor of activated T cells (NFAT) transcription factor NFATp (NFATc2) is a repressor of chondrogenesis.

Ranger AM, Gerstenfeld LC, Wang J, Kon T, Bae H, Gravallese EM, Glimcher MJ, Glimcher LH - J. Exp. Med. (2000)

Absence of NFATp enhances, whereas overexpression of NFATp represses the cartilage phenotype. (A) RT-PCR analysis of mature cartilage gene expression in primary wt and NFATp−/− articular chondrocytes using types II and X collagen and HPRT primers. (B) Western blot analysis of S12 and EA control (Rep) and NFATp transfectants with anti-NFATp antibody. (C) RT-PCR analysis of mature cartilage gene expression of S12 and EA control and NFATp transfectants using type II collagen, type X collagen, CDMP-1, and actin primers (references 36–38).
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2195796&req=5

Figure 5: Absence of NFATp enhances, whereas overexpression of NFATp represses the cartilage phenotype. (A) RT-PCR analysis of mature cartilage gene expression in primary wt and NFATp−/− articular chondrocytes using types II and X collagen and HPRT primers. (B) Western blot analysis of S12 and EA control (Rep) and NFATp transfectants with anti-NFATp antibody. (C) RT-PCR analysis of mature cartilage gene expression of S12 and EA control and NFATp transfectants using type II collagen, type X collagen, CDMP-1, and actin primers (references 36–38).
Mentions: The uncontrolled proliferation of resident connective tissue cells and their differentiation to cartilage cells and the proliferation of existing articular cartilage cells, coupled with the regulated expression of NFATp in MSC cultures, suggested that NFATp represses the chondrogenic program. To further investigate this possibility, we took two approaches. First, we compared the levels of transcripts for type II and X collagen by semiquantitative RT-PCR in primary articular chondrocytes established from wt and NFATp−/− femoral heads. Fig. 5 A demonstrates that articular chondrocytes lacking NFATp have much higher (at least eightfold) levels of both type II and X collagen mRNA than wt articular cartilage cells.

Bottom Line: Consistent with these data, NFATp expression is regulated in mesenchymal stem cells induced to differentiate along a chondrogenic pathway.Lack of NFATp in articular cartilage cells results in increased expression of cartilage markers, whereas overexpression of NFATp in cartilage cell lines extinguishes the cartilage phenotype.Thus, NFATp is a repressor of cartilage cell growth and differentiation and also has the properties of a tumor suppressor.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.

ABSTRACT
Nuclear factor of activated T cells (NFAT) transcription factors regulate gene expression in lymphocytes and control cardiac valve formation. Here, we report that NFATp regulates chondrogenesis in the adult animal. In mice lacking NFATp, resident cells in the extraarticular connective tissues spontaneously differentiate to cartilage. These cartilage cells progressively differentiate and the tissue undergoes endochondral ossification, recapitulating the development of endochondral bone. Proliferation of already existing articular cartilage cells also occurs in some older animals. At both sites, neoplastic changes in the cartilage cells occur. Consistent with these data, NFATp expression is regulated in mesenchymal stem cells induced to differentiate along a chondrogenic pathway. Lack of NFATp in articular cartilage cells results in increased expression of cartilage markers, whereas overexpression of NFATp in cartilage cell lines extinguishes the cartilage phenotype. Thus, NFATp is a repressor of cartilage cell growth and differentiation and also has the properties of a tumor suppressor.

Show MeSH
Related in: MedlinePlus