Osteoblast-specific expression of Fra-2/AP-1 controls Adiponectin/Osteocalcin expression and affects metabolism

Abstract

SummaryRecent 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.

Terminal epidermal differentiation is regulated by the interaction of Fra-2/AP-1 with Ezh2 and ERK1/2

“…Fra-2 Dep mice were generated by crossing Fra-2 f/f mice with mice expressing Cre recombinase from the K5 promoter (Zenz et al 2005). Control (Cre-negative mice), Fra Fra-2 Ep-tetOFF mice were generated by crossing mice carrying a Flag-tagged Fra-2 cDNA knock-in controlled by a tetracycline operator downstream from the col1a1 gene (col Fra-2 +/KI ) (Bozec et al 2013) to mice expressing tTA from the K5 promoter (Diamond et al 2000). ) were identified by genotyping PCR on tail biopsies.…”

FOSL2 Positively Regulates TGF-β1 Signalling in Non-Small Cell Lung Cancer

“…The various FOS proteins play key roles in distinct developmental, physiological, and pathological processes [6], but these individual roles and the mechanisms involved are not yet clear. FOSL2 exerts a specific function in bone development [7] and appears to have selective physiological and pathological roles in diverse processes, including photoperiodic regulation [8], cancer [9], and fibrosis [10]. Several previous studies have indicated that FOSL2 plays a key role in the regulation of TGF-β pathway.…”

The Expression Level of mRNA, Protein, and DNA Methylation Status of FOSL2 of Uyghur in XinJiang in Type 2 Diabetes

“…The Fos gene family plays an important role in cell differentiation and proliferation [19]. Meanwhile, FOSL2 gene expression has been linked to fat metabolism, cancer, and bone diseases in human and animals [14, 20–22]. …”

“…The Fos gene family is constituted by FOSL2, FOS, FOSB, and FOSI , and FOSL2 has been described in many different tissue types in both animals and humans [13]. Recent studies have found that it plays a crucial role in forming fat cells; meanwhile, some researchers have demonstrated that metabolism can be affected by FOSL2 expression [14, 15]. …”