UMMS Affiliation
Department of Medicine, Division of Rheumatology
Publication Date
1-3-2000
Document Type
Article
Subjects
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
Disciplines
Cancer Biology | Cell Biology | Cellular and Molecular Physiology
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.
Keywords
cartilage, NFATp, mesenchymal stem cells, chondrosarcoma, differentiation
Rights and Permissions
Publisher PDF posted as allowed by the publisher's author rights policy at http://www.rupress.org/site/subscriptions/terms.xhtml.
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DOI of Published Version
10.1084/jem.191.1.9
Source
J Exp Med. 2000 Jan 3;191(1):9-22. doi: 10.1084/jem.191.1.9. Link to article on publisher's website
Journal/Book/Conference Title
The Journal of experimental medicine
Related Resources
PubMed ID
10620601
Repository Citation
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.
https://escholarship.umassmed.edu/rheumatology_pubs/26
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 3.0 License
Comments
At the time of publication, Ellen Gravallese was not yet affiliated with the University of Massachusetts Medical School.