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Impaired bone formation in Pdia3 deficient mice
Yun Wang1, Alexandr Nizkorodov1, Kelsie Riemenschneider1
1Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States of America.
Plos One
|November 19, 2014
Summary
Protein disulfide isomerase family A, member 3 (PDIA3) is essential for skeletal development. PDIA3 deficiency causes embryonic lethality and skeletal abnormalities, suggesting its critical role in bone homeostasis and vitamin D signaling.
Area of Science:
- Molecular Biology
- Developmental Biology
- Endocrinology
Background:
- 1α,25-Dihydroxyvitamin D3 [1α,25(OH)2D3] is vital for skeletal development and bone homeostasis.
- Protein disulfide isomerase family A, member 3 (PDIA3) is known to mediate rapid membrane signaling initiated by 1α,25(OH)2D3.
Purpose of the Study:
- To investigate the role of PDIA3 in skeletal development and bone homeostasis.
- To determine the physiological consequences of Pdia3 gene disruption in mice.
Main Methods:
- Generation of Pdia3-deficient mice (homozygous and heterozygous).
- Analysis of embryonic lethality and skeletal phenotypes using micro-computed tomography (µCT) and histomorphometry.
- Assessment of osteoblastic differentiation in bone marrow cells.
Main Results:
- Targeted disruption of Pdia3 resulted in early embryonic lethality.
- Pdia3 heterozygous mice exhibited expanded growth plates, decreased tether formation, and increased cellularity in the hypertrophic zone.
- Age-dependent reduction in bone volume and trabecular number was observed in Pdia3+/- mice, along with impaired osteoblastic differentiation.
Conclusions:
- PDIA3 is essential for normal skeletal development in vivo.
- PDIA3-mediated rapid membrane signaling may represent an alternative mechanism for 1α,25(OH)2D3's skeletal actions, similar to VDR-mediated pathways.
