The nuclear factor of activated T cells (NFAT) transcription factor NFATp (NFATc2) is a repressor of chondrogenesis

Nuclear factor of activated T cells (NFAT) transcription factors regulate g ene expression in lymphocytes and control cardiac valve formation. Here, we report that NFATp regulates chondrogenesis in the adult animal. In mice la cking NFATp, resident cells in the extraarticular connective tissues sponta neously differentiate to cartilage. These cartilage cells progressively dif ferentiate and the tissue undergoes endochondral ossification, recapitulati ng 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 dat a, NFATp expression is regulated in mesenchymal stem cells induced to diffe rentiate along a chondrogenic pathway. Lack of NFATp in articular cartilage cells results in increased expression of cartilage markers, whereas overex pression of NFATp in cartilage cell lines extinguishes the cartilage phenot ype. Thus, NFATp is a repressor of cartilage cell growth and differentiatio n and also has the properties of a tumor suppressor.