{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:18:33Z","timestamp":1790252313307,"version":"4.1.0"},"reference-count":51,"publisher":"The Company of Biologists","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,5,1]]},"abstract":"<jats:p>A shift from osteoblastogenesis to adipogenesis is one of the underlying mechanisms of decreased bone mass and increased fat during aging. We now uncover a new role for the transcription factor Fra-1 in suppressing adipogenesis. Indeed, Fra1 (Fosl1) transgenic (Fra1tg) mice, which developed progressive osteosclerosis as a result of accelerated osteoblast differentiation, also developed a severe general lipodystrophy. The residual fat of these mice appeared immature and expressed lower levels of adipogenic markers, including the fatty acid transporter Cd36 and the CCAAT\/enhancer binding protein Cebpa. Consequently accumulation of triglycerides and free fatty acids were detected in the serum of fasting Fra1tg mice. Fra-1 acts cell autonomously because the adipogenic differentiation of Fra1 transgenic primary osteoblasts was drastically reduced, and overexpression of Fra-1 in an adipogenic cell line blocked their differentiation into adipocytes. Strikingly, Cebpa was downregulated in the Fra-1-overexpressing cells and Fra-1 could bind to the Cebpa promoter and directly suppress its activity. Thus, our data add to the known common systemic control of fat and bone mass, a new cell-autonomous level of control of cell fate decision by which the osteogenic transcription factor Fra-1 opposes adipocyte differentiation by inhibiting C\/EBP\u03b1.<\/jats:p>","DOI":"10.1242\/jcs.079855","type":"journal-article","created":{"date-parts":[[2011,4,13]],"date-time":"2011-04-13T02:22:58Z","timestamp":1302661378000},"page":"1465-1476","source":"Crossref","is-referenced-by-count":47,"title":["Elevated Fra-1 expression causes severe lipodystrophy"],"prefix":"10.1242","volume":"124","author":[{"given":"Julia","family":"Luther","sequence":"first","affiliation":[{"name":"Department of Internal Medicine 3, Rheumatology and Immunology, University of Erlangen-Nuremberg, D91054 Erlangen, Germany"},{"name":"Group Bone Cell Differentiation, Deutsches Rheuma-Forschungszentrum (DRFZ), D10117 Berlin, 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