title: Osteoblast-specific expression of Fra-2/AP-1 controls adiponectin and osteocalcin expression and affects metabolism.
abstract: Recent studies have established that the skeleton functions as an endocrine organ affecting metabolism through the osteoblast-derived hormone osteocalcin (Ocn). However, it is not fully understood how many transcription factors expressed in osteoblasts regulate the endocrine function. Here, we show that mice with osteoblast-specific deletion of Fra-2 (Fosl2) have low bone mass but increased body weight. In contrast, transgenic expression of Fra-2 in osteoblasts leads to increased bone mass and decreased body weight accompanied by reduced serum glucose and insulin levels, improved glucose tolerance and insulin sensitivity. In addition, mice lacking Fra-2 have reduced levels of circulating Ocn, but high adiponectin (Adipoq), whereas Fra-2 transgenic mice exhibit high Ocn and low Adipoq levels. Moreover, we found that Adipoq was expressed in osteoblasts and that this expression was transcriptionally repressed by Fra-2. These results demonstrate that Fra-2 expression in osteoblasts represents a novel paradigm for a transcription factor controlling the endocrine function of the skeleton.
authors.affiliation: Genes, Development and Disease Group, F-BBVA-CNIO Cancer Cell Biology Program, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
authors.forename: Aline
authors.initials: A
authors.lastname: Bozec
authors.forename: Latifa
authors.initials: L
authors.lastname: Bakiri
authors.forename: Maria
authors.initials: M
authors.lastname: Jimenez
authors.forename: Evan D
authors.initials: ED
authors.lastname: Rosen
authors.forename: Philip
authors.initials: P
authors.lastname: Catalá-Lehnen
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schinke
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
authors.forename: Michael
authors.initials: M
authors.lastname: Amling
authors.forename: Erwin F
authors.initials: EF
authors.lastname: Wagner
mesh_terms: D052242:Adiponectin / Q000097:blood / Q000235:genetics*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D051921:Fos-Related Antigen-2 / Q000172:deficiency / Q000235:genetics*; D005786:Gene Expression Regulation; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D015675:Osteocalcin / Q000097:blood / Q000235:genetics*; D015398:Signal Transduction; D012886:Skull / Q000166:cytology / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D051921:Fos-Related Antigen-2; C497873:Fosl2 protein, mouse; D007328:Insulin; D018808:Transcription Factor AP-1; D015675:Osteocalcin
keywords: AP-1; Activator protein 1; Adiponectin; Fosl2; Fra-2; Metabolism; Osteoblasts; Osteocalcin