Disruption of Pdia3 gene results in bone abnormality and affects 1α,25-dihydroxy-vitamin D3-induced rapid activation of PKC

Yun Wang, Jiaxuan Chen, Christophe S.D. Lee, Alexandr Nizkorodov, Kelsie Riemenschneider, David Martin, Sharon Hyzy, Zvi Schwartz, Barbara D. Boyan

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

1,25-Dihydroxy-vitamin D3 [1α,25(OH)2D3] is a critical regulator of bone development. Protein disulfide isomerase A3 (Pdia3) is a multifunctional protein that has been associated with rapid membrane-initiated signalling by 1α,25(OH)2D3 in several cell types. To identify the physiological roles of Pdia3 in skeletal development, we generated Pdia3-deficient mice. No homozygous mice were observed at birth, indicating that the targeted disruption of the Pdia3 gene resulted in embryonic lethality. Pdia3 deficiency also resulted in skeletal manifestations as revealed by μCT analysis of femurs from 15-week-old heterozygous mice. The Pdia3+/- mice had increased metaphyseal bone volume and trabeculae compared to Pdia3+/+ mice. In contrast, the area and thickness of cortical bone at the femoral mid-diaphysis of Pdia3+/+ mice significantly exceeded that of Pdia3+/- mice. In vitro studies in osteoblast-like MC3T3-E1 cells showed that silencing of Pdia3 abolished 1α,25(OH)2D3-induced rapid activation of protein kinase C (PKC) while overexpression of Pdia3 resulted in augmentation of PKC activity by 1α,25(OH)2D3. Taken together, these data indicated that Pdia3 plays a crucial role in 1α,25(OH)2D3-regulated bone formation and the Pdia3-PKC signalling pathway might be involved in this process.

Original languageEnglish (US)
Pages (from-to)257-260
Number of pages4
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume121
Issue number1-2
DOIs
StatePublished - Jul 1 2010

Keywords

  • 1α,25(OH)2D3
  • Bone
  • Global knockout
  • Osteoblast
  • Pdia3
  • Vitamin D3

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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    Wang, Y., Chen, J., Lee, C. S. D., Nizkorodov, A., Riemenschneider, K., Martin, D., Hyzy, S., Schwartz, Z., & Boyan, B. D. (2010). Disruption of Pdia3 gene results in bone abnormality and affects 1α,25-dihydroxy-vitamin D3-induced rapid activation of PKC. Journal of Steroid Biochemistry and Molecular Biology, 121(1-2), 257-260. https://doi.org/10.1016/j.jsbmb.2010.05.004