Osterix:nlGFP transgenic medaka identify regulatory roles for retinoic acid signaling during osteoblast differentiation in vivo

Abstract

Summary Recent findings suggest that retinoic acid (RA) plays an important role for osteoblast differentiation and function in mammals as well as teleost fish. In this study, we show that treatment of medaka embryos with retinoic acid leads to an over-ossification in the cranial and axial skeleton, while inhibition of endogenous RA synthesis reduces bone ossification. Using transgenic medaka carrying the osterix (osx) promoter to drive osteoblast-specific reporter gene expression, we show that an increase of retinoic acid levels leads to mis-localization of osx expressing osteoblasts and condensed transgenic expression in the axial skeleton, while inhibition of RA synthesis reduces the number of osx positive cells and consequently bone ossification. Our in vivo data suggest that distinct RA levels are necessary to control differentiation of early osteoblasts and promote the mineralizing activity of mature osteoblasts.