OASIS, an endoplasmic reticulum stress transducer, is involved in bone formation

Abstract

OASIS (Old Astrocyte Specifically Induced Substance) is a bZIP transcription factor of the CREB/ATF family with a transmembrane domain. OASIS is cleaved at the membrane in response to endoplasmic reticulum (ER) stress. Its cleaved cytoplasmic domain translocates into the nucleus where it activates the transcription of target genes. OASIS is selectively expressed in some types of cells such as astrocytes and osteoblasts. Previously, we demonstrated that OASIS activates the transcription of the gene for type I collagen, Col1a1, and contributes to the secretion of bone matrix proteins in osteoblasts. OASIS−/− mice exhibit severe osteopenia and growth retardation. The osteopenia resulted from a decrease in type I collagen in the bone matrix and a dysfunction of osteoblasts, which show abnormal expansion of the ER with the accumulation of bone matrix proteins. To examine whether the phenotypes of OASIS−/− mice are rescued by OASIS transgene in osteoblasts, we generated transgenic mice that express exogenous OASIS specifically in osteoblasts (obOASIS mice). Introduction of exogenous OASIS in osteoblasts rescued severe osteopenia observed in OASIS−/− mice. In contrast, that could not improve the growth retardation in OASIS−/− mice. These results indicated that the growth retardation observed in OASIS−/− mice could be caused by other mechanisms different from osteoblast dysfunction.