UMMS Affiliation

Department of Medicine, Division of Rheumatology

Publication Date

2000-01-03

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.

Beginning six months after publication, RUP grants the public the non-exclusive right to copy, distribute, or display the Work under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license

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

Comments

At the time of publication, Ellen Gravallese was not yet affiliated with the University of Massachusetts Medical School.

Related Resources

Link to Article in PubMed

PubMed ID

10620601

Creative Commons License

Creative Commons Attribution-Noncommercial 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial 3.0 License

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