The nuclear factor of activated T cells (NFAT) transcription factor NFATp (NFATc2) is a repressor of chondrogenesis
Ranger, Ann M. ; Gerstenfeld, Louis C. ; Wang, Jinxi ; Kon, Tamiyo ; Bae, Hyunsu ; Gravallese, Ellen M. ; Glimcher, Melvin J. ; Glimcher, Laurie H.
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Keywords
Bone Development
Bone and Bones
Cartilage
Cell Differentiation
Cell Division
*Chondrogenesis
DNA-Binding Proteins
Genes, Tumor Suppressor
Mice
Mice, Inbred BALB C
Mice, Knockout
NFATC Transcription Factors
*Nuclear Proteins
Stem Cells
Transcription Factors
cartilage
NFATp
mesenchymal stem cells
chondrosarcoma
differentiation
Cancer Biology
Cell Biology
Cellular and Molecular Physiology
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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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J Exp Med. 2000 Jan 3;191(1):9-22. doi: 10.1084/jem.191.1.9. Link to article on publisher's website
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Notes
At the time of publication, Ellen Gravallese was not yet affiliated with the University of Massachusetts Medical School.