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.
Author keywords
Cartilage; Chondrosarcoma; Differentiation; Mesenchymal stem cells; NFATp
Indexed keywords
EMTREE drug terms: nuclear factor; transcription factor
EMTREE medical terms: animal cell; animal experiment; animal tissue; article; articular cartilage; cartilage cell; cell differentiation; chondrogenesis; controlled study; enchondral ossification; gene expression regulation; mesenchyme; mouse; nonhuman; priority journal; repressor gene; stem cell; T lymphocyte activation; tumor suppressor gene
MeSH: Animals; Bone and Bones; Bone Development; 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
Medline is the source for the MeSH terms of this document.
Chemicals and CAS Registry Numbers: DNA-Binding Proteins; NFATC Transcription Factors; Nfatc2 protein, mouse; Nuclear Proteins; Transcription Factors