UNLABELLED: 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 (Osr2DeltaN) 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 Osr2DeltaN transgenic mice skeletons stained with alcian blue and alizarin red showed reduced intensities in the skull and skeletal elements. Morphologically, calvariae and tibias of Osr2DeltaN 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 Osr2DeltaN 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.
UNLABELLED: We report that Osr2 is one of the regulators of osteoblast function, because dominant-negative Osr2transgenic 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 (Osr2DeltaN) 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 Osr2DeltaNtransgenic mice skeletons stained with alcian blue and alizarin red showed reduced intensities in the skull and skeletal elements. Morphologically, calvariae and tibias of Osr2DeltaNtransgenic 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 Osr2DeltaNtransgenic 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.
Authors: Joel L Frandsen; Bronwyn Gunn; Selen Muratoglu; Nancy Fossett; Stuart J Newfeld Journal: Proc Natl Acad Sci U S A Date: 2008-09-24 Impact factor: 11.205
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