Department of Medicine, Division of Rheumatology
Animals; 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
Cancer Biology | Cell Biology | Cellular and Molecular Physiology
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.
cartilage, NFATp, mesenchymal stem cells, chondrosarcoma, differentiation
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DOI of Published Version
J Exp Med. 2000 Jan 3;191(1):9-22. doi: 10.1084/jem.191.1.9. Link to article on publisher's website
The Journal of experimental medicine
Ranger, Ann M.; Gerstenfeld, Louis C.; Wang, Jinxi; Kon, Tamiyo; Bae, Hyunsu; Gravallese, Ellen M.; Glimcher, Melvin J.; and Glimcher, Laurie H., "The nuclear factor of activated T cells (NFAT) transcription factor NFATp (NFATc2) is a repressor of chondrogenesis" (2000). Rheumatology Publications and Presentations. 26.
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This work is licensed under a Creative Commons Attribution-Noncommercial 3.0 License