Zinc-Finger Transcription Factor Odd-Skipped Related 2 Is One of the Regulators in Osteoblast Proliferation and Bone Formation

Abstract

We report that Osr2 is one of the regulators of osteoblast function, because dominant-negative Osr2 transgenic mice exhibited decreased osteoblast activity and delayed mineralization in calvarial and tibial bone tissues. Our results indicate that Osr2 functions in regulation of osteoblast proliferation.Introduction: Molecular mechanisms that control bone formation have received attention with increasing knowledge related to genetic control of osteoblast differentiation. The odd-skipped related (Osr) gene is a zinc-finger transcription factor recently suggested to be involved in bone formation, although little is known about its role. Materials and Methods: To elucidate the in vivo function of Osr2, we generated transgenic mice overexpressing dominant-negative Osr2. Results: In this study, N-terminal-deleted Osr2 was found to act as a dominant-negative mutant toward both Osr1 and Osr2. Dominant-negative Osr2 (Osr2⌬N) transgenic mice showed delayed mineralization in calvarial and cortical bone tissues. Furthermore, soft X-ray analysis of transgenic mice bones revealed distinctly increased radiolucency. Examinations of newborn Osr2⌬N transgenic mice skeletons stained with alcian blue and alizarin red showed reduced intensities in the skull and skeletal elements. Morphologically, calvariae and tibias of Osr2⌬N transgenic mice were composed of markedly thinner parietal and cortical bones and lower numbers of osteoblastic cells on bone surfaces, indicating a reduced proliferation of osteoblasts. Furthermore, calvarial osteoblasts obtained from Osr2⌬N transgenic mice showed highly attenuated osteoblast differentiation and proliferation, confirming that Osr2 is needed for osteogenesis. Finally, results of Runx2-deficient cell assays suggested that Osr2 induces alkaline phosphatase (ALP) expression, but to a lesser degree than Runx2-expressing cells. Conclusions: Our genetic observations showed that the Osr2 gene plays a key role in osteoblastic cell proliferation.

Odd-skipped related-1 controls neural crest chondrogenesis during tongue development

“…Although the specific Osr1-binding DNA sequence has not been reported, a previous PCR-based DNA-binding sequence selection study suggested that the mouse Osr2 protein binds to a core DNA sequence similar to that bound by the Drosophila odd-skipped protein (36,37). Osr1 and Osr2 share almost identical DNA-binding domains (11).…”

Effects of thirty elements on bone metabolism

“…Alkaline phosphatase, collagenase, and aminoacyl-tRNA synthetase are some of the zinc-dependent enzymes, which can impact bone metabolism and are likely to be affected by imbalanced zinc levels [64,315,318]. Gli-similar 3 (Glis3) and Odd-skipped related 2 (Osr2) are zinc finger transcription factors that promote osteoblast differentiation [319,320]. Zinc may also affect several aspects of osteoblast differentiation, presumably by modulating gene expression of runtrelated transcription factor 2 (Runx2) [321,322].…”

Theosr1andosr2genes act in the pronephric anlage downstream of retinoic acid signaling and upstream ofwnt2bto maintain pectoral fin development

“…Analysis of mutant lines has indicated that these genes are required for proper formation and/or patterning of the endoderm, the heart, the teeth, the palate, the bones and the synovial joints in the limbs (Gao et al, 2011;Kawai et al, 2007;Lan et al, 2004;Mudumana et al, 2008;Wang et al, 2005;Zhang et al, 2009). Expression studies in mice and chicken indicate that, in the limb, Osr genes are expressed from very early stages in a highly dynamic pattern (Lan et al, 2001;So and Danielian, 1999;Stricker et al, 2006).…”