Zinc-finger transcription factor Odd-skipped related 1 regulates cranial bone formation

• Published in: Journal of bone and mineral metabolism Vol. 36; no. 6; pp. 640 - 647
• Main Authors: Kawai, Shinji, Yamauchi, Masashi, Amano, Atsuo
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.11.2018; Springer Nature B.V
• Subjects: Alkaline phosphatase; Animals; Bone growth; Bone morphogenetic protein 2; Bone Morphogenetic Protein 2 - pharmacology; Cell Differentiation - drug effects; Cell Differentiation - genetics; Cell Line; Cell proliferation; Cell Proliferation - drug effects; Cell Proliferation - genetics; Cells, Cultured; Chondrocytes; Embryogenesis; Gene Expression Regulation - drug effects; Genetic control; Medicine; Medicine & Public Health; Mesenchyme; Metabolic Diseases; Mice, Transgenic; Molecular modelling; Original Article; Orthopedics; Osteoblasts; Osteocalcin; Osteogenesis; Osteogenesis - drug effects; Osteogenesis - genetics; Phenotype; siRNA; Skull; Skull - growth & development; Skull - metabolism; Transcription Factors - metabolism; Transgenic animals; Transgenic mice; Zinc finger proteins; Zinc Fingers; Osteoblast; Cranium; Bone formation; Transcription factor; Transgenic mice
• ISSN: 0914-8779; 1435-5604
• DOI: 10.1007/s00774-017-0885-9

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.