Abstract
Knowledge of the molecular mechanisms of bone formation has been advanced by novel findings related to genetic control. Odd-skipped related 1 (Osr1) is known to play important roles in embryonic, heart, and urogenital development. To elucidate the in vivo function of Osr1 in bone formation, we generated transgenic mice overexpressing full-length Osr1 under control of its 2.8-kb promoter, which were smaller than their wild-type littermates. Notably, abnormalities in the skull of Osr1 transgenic mice were revealed by analysis of X-ray, skeletal preparation, and morphological findings, including round skull and cranial dysraphism. Furthermore, primary calvarial cells obtained from these mice showed increased proliferation and expression of chondrocyte markers, while expression of osteoblast markers was decreased. BMP2 reduced Osr1 expression and Osr1 knockdown by siRNA-induced alkaline phosphatase and osteocalcin expression in mesenchymal and osteoblastic cells. Together, our results suggest that Osr1 plays a coordinating role in appropriate skull closure and cranial bone formation by negative regulation.
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Acknowledgements
We thank all the members of the Challenge to Intractable Oral Diseases and Center for Frontier Oral Science for their assistance and encouragement, as well as Mark Benton for their comments regarding our manuscript. This work was supported by Grants-in-Aid for Scientific Research from the Japanese Society for the Promotion of Science (KAKENHI no. C21592356, C24592796), and by special funds for Challenge to Intractable Oral Diseases.
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Kawai, S., Yamauchi, M. & Amano, A. Zinc-finger transcription factor Odd-skipped related 1 regulates cranial bone formation. J Bone Miner Metab 36, 640–647 (2018). https://doi.org/10.1007/s00774-017-0885-9
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DOI: https://doi.org/10.1007/s00774-017-0885-9