Advertisement

Journal of Bone and Mineral Metabolism

, Volume 36, Issue 6, pp 640–647 | Cite as

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

  • Shinji Kawai
  • Masashi Yamauchi
  • Atsuo Amano
Original Article

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.

Keywords

Osteoblast Bone formation Transcription factor Cranium Transgenic mice 

Notes

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.

Conflict of interest

All authors declare that they have no competing interests.

References

  1. 1.
    Coulter DE, Swaykus EA, Beran-Koehn MA, Goldberg D, Wieschaus E et al (1990) Molecular analysis of odd-skipped, a zinc finger encoding segmentation gene with a novel pair-rule expression pattern. EMBO J 9:3795–3804CrossRefGoogle Scholar
  2. 2.
    So PL, Danielian PS (1999) Cloning and expression analysis of a mouse gene related to Drosophila odd-skipped. Mech Dev 84:157–160CrossRefGoogle Scholar
  3. 3.
    Katoh M (2002) Molecular cloning and characterization of OSR1 on human chromosome 2p24. Int J Mol Med 10:221–225PubMedGoogle Scholar
  4. 4.
    Kawai S, Michikami I, Kitagaki J, Hashino E, Amano A (2013) Expression pattern of zinc-finger transcription factor Odd-skipped related 2 in murine development and neonatal stage. Gene Expr Patterns 13:372–376CrossRefGoogle Scholar
  5. 5.
    Wang Q, Lan Y, Cho ES, Maltby KM, Jiang R (2005) Odd-skipped related 1 (Odd 1) is an essential regulator of heart and urogenital development. Dev Biol 288:582–594CrossRefGoogle Scholar
  6. 6.
    Kawai S, Yamauchi M, Wakisaka S, Ooshima T, Amano A (2007) Zinc-finger transcription factor odd-skipped related 2 is one of the regulators in osteoblast proliferation and bone formation. J Bone Miner Res 22:1362–1372CrossRefGoogle Scholar
  7. 7.
    Yamauchi M, Kawai S, Kato T, Ooshima T, Amano A (2008) Odd-skipped related 1 gene expression is regulated by Runx2 and Ikzf1 transcription factors. Gene 426:81–90CrossRefGoogle Scholar
  8. 8.
    Deng ZL, Sharff KA, Tang N, Song WX, Luo J et al (2008) Regulation of osteogenic differentiation during skeletal development. Front Biosci 13:2001–2021CrossRefGoogle Scholar
  9. 9.
    Gordon JW, Scangos GA, Plotkin DJ, Barbosa JA, Ruddle FH (1980) Genetic transformation of mouse embryos by microinjection of purified DNA. Proc Natl Acad Sci USA 77:7380–7384CrossRefGoogle Scholar
  10. 10.
    McLeod MJ (1980) Differential staining of cartilage and bone in whole mouse fetuses by alcian blue and alizarin red S. Teratology 22:299–301CrossRefGoogle Scholar
  11. 11.
    Lyle HM (1947) An improved tissue technique with hematoxylin-eosin stain. Am J Med Technol 13:178–181PubMedGoogle Scholar
  12. 12.
    Farley JR, Tarbaux NM, Hall SL, Linkhart TA, Baylink DJ (1988) The anti-bone-resorptive agent calcitonin also acts in vitro to directly increase bone formation and bone cell proliferation. Endocrinology 123:159–167CrossRefGoogle Scholar
  13. 13.
    Rawadi G, Vayssiere B, Dunn F, Baron R, Roman-Roman S (2003) BMP-2 controls alkaline phosphatase expression and osteoblast mineralization by a Wnt autocrine loop. J Bone Miner Res 18:1842–1853CrossRefGoogle Scholar
  14. 14.
    Barrell WB, Szabo-Rogers HL, Liu KJ (2012) Novel reporter alleles of GSK-3alpha and GSK-3beta. PLoS One 7:e50422CrossRefGoogle Scholar
  15. 15.
    Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K et al (1997) Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 89:755–764CrossRefGoogle Scholar
  16. 16.
    Liu YH, Kundu R, Wu L, Luo W, Ignelzi MA Jr et al (1995) Premature suture closure and ectopic cranial bone in mice expressing Msx2 transgenes in the developing skull. Proc Natl Acad Sci USA 92:6137–6141CrossRefGoogle Scholar
  17. 17.
    Atsawasuwan P, Lu X, Ito Y, Zhang Y, Evans CA et al (2013) Ameloblastin inhibits cranial suture closure by modulating MSX2 expression and proliferation. PLoS One 8:e52800CrossRefGoogle Scholar
  18. 18.
    Park MH, Shin HI, Choi JY, Nam SH, Kim YJ et al (2001) Differential expression patterns of Runx2 isoforms in cranial suture morphogenesis. J Bone Miner Res 16:885–892CrossRefGoogle Scholar
  19. 19.
    Otto F, Kanegane H, Mundlos S (2002) Mutations in the RUNX2 gene in patients with cleidocranial dysplasia. Hum Mutat 19:209–216CrossRefGoogle Scholar
  20. 20.
    James RG, Schultheiss TM (2005) Bmp signaling promotes intermediate mesoderm gene expression in a dose-dependent, cell-autonomous and translation-dependent manner. Dev Biol 288:113–125CrossRefGoogle Scholar
  21. 21.
    James RG, Kamei CN, Wang Q, Jiang R, Schultheiss TM (2006) Odd-skipped related 1 is required for development of the metanephric kidney and regulates formation and differentiation of kidney precursor cells. Development 133:2995–3004CrossRefGoogle Scholar
  22. 22.
    Zhang Z, Iglesias D, Eliopoulos N, El Kares R, Chu L et al (2011) A variant OSR1 allele which disturbs OSR1 mRNA expression in renal progenitor cells is associated with reduction of newborn kidney size and function. Hum Mol Genet 20:4167–4174CrossRefGoogle Scholar

Copyright information

© The Japanese Society for Bone and Mineral Research and Springer Japan KK, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Challenge to Intractable Oral Diseases, Center for Frontier Oral ScienceOsaka University Graduate School of DentistrySuitaJapan
  2. 2.Department of Pediatric DentistryOsaka University Graduate School of DentistryOsakaJapan
  3. 3.Department of Preventive DentistryOsaka University Graduate School of DentistryOsakaJapan

Personalised recommendations