Protein disulfide isomerase (PDI) is an oxidoreductase responsible for the formation, reduction and isomerization of disulfide bonds of nascent proteins in endoplasmic reticulum (ER). So far, the role of PDI in bone biology has never been characterized using genetically-modified animal models. In this study we generated osteoblast- specific PDI-deficient mice by crossing PDI-floxed (PDI) mice with Osx-Cre mice. Compared with their littermate control PDI mice, homozygous osteoblast-knockout mice (Osx-Cre/PDI) were embryonically lethal, but heterozygous knockout mice (Osx-Cre/PDI) displayed significantly pronounced growth retardation and reduced bone length. Besides, the decreases in bone density, osteoblast and osteoclast numbers, collagen fiber content and bone formation rate were observed in Osx-Cre/PDI mice. Osteoblast precursors isolated from PDI mice were infected with Cre recombinant adenovirus to produce PDI-deficient osteoblasts, followed by induction of differentiation. Osteoblasts deficient of PDI had decreased alkaline phosphatase activity, mineralizing capacity, and differentiation. Quantitative protein mass spectrometry analysis and immunoblotting showed that PDI deficiency markedly decreased the expression of the α-subunits of collagen prolyl 4-hydroxylase (C-P4H), including P4HA1, P4HA2 and P4HA3. These results demonstrate that PDI plays an essential role in osteoblast differentiation and bone formation and is required for the expression of the α-subunit of C-P4H in osteoblasts.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/s42003-025-07824-3 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Protein disulfide isomerase is essential for osteoblast differentiation in mice.
Commun Biol
March 2025
Cyrus Tang Medical Institute, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow University, Suzhou, 215123, China.
Protein disulfide isomerase (PDI) is an oxidoreductase responsible for the formation, reduction and isomerization of disulfide bonds of nascent proteins in endoplasmic reticulum (ER). So far, the role of PDI in bone biology has never been characterized using genetically-modified animal models. In this study we generated osteoblast- specific PDI-deficient mice by crossing PDI-floxed (PDI) mice with Osx-Cre mice.
View Article and Find Full Text PDFProtein disulfide isomerase integrates toll-like receptor 4 and P2X7 receptor signaling pathways during lipopolysaccharide-induced neuroinflammation.
Sci Rep
March 2025
Department of Anatomy and Neurobiology, College of Medicine, Hallym University, Chuncheon, 24252, Korea.
P2X7 receptor (P2X7R) augments lipopolysaccharide (LPS)-toll-like receptor 4 (TLR4)-mediated neuroinflammation. These roles of P2X7R in neuroinflammation are relevant to nitrosative stress through nuclear factor-κB (NF-κB)-inducible nitric oxide synthase (iNOS) pathway, while the underlying mechanisms are largely unknown. In the present study, we investigated whether protein disulfide isomerase (PDI) is involved in the integration of TLR4-P2X7R functions in response to LPS in vivo.
View Article and Find Full Text PDFThe combination of flaxseed lignans and PD-1/ PD-L1 inhibitor inhibits breast cancer growth via modulating gut microbiome and host immunity.
Drug Resist Updat
February 2025
Heilongjiang Clinical Research Center for Breast Cancer, Harbin Medical University Cancer Hospital, Harbin, China; Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China. Electronic address:
Background: Patients with breast cancer (BC) who benefit from the PD-1/PD-L1 inhibitor (PDi) is limited, necessitating novel strategies to improve immunotherapy efficacy of BC. Here we aimed to investigate the inhibitory effects of flaxseed lignans (FL) on the biological behaviors of BC and evaluate the roles of FL in enhancing the anticancer effects of PDi.
Methods: HPLC was used to detect the content of enterolactone (ENL), the bacterial transformation product of FL.
Cascade-recharged macrophage-biomimetic ruthenium-based nanobattery for enhanced photodynamic-induced immunotherapy.
J Nanobiotechnology
March 2025
Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, 830017, China.
Photodynamic-induced immunotherapy (PDI) is often hampered by low reactive oxygen species (ROS) yield, intra-tumor hypoxia, high glutathione (GSH) concentration, and immunosuppressive microenvironment. In view of this, a ruthenium (Ru)-based nanobattery (termed as IRD) with cascade-charged oxygen (O), ROS, and photodynamic-induced immunotherapy by coordination-driven self-assembly of transition-metal Ru, photosensitizer indocyanine green (ICG), and organic ligand dithiobispropionic acid (DTPA). Then, IRD is camouflaged with macrophage membranes to obtain a nanobattery (termed as IRD@M) with targeting and immune evasion capabilities.
View Article and Find Full Text PDFRole of HNF4A-AS1/HNRNPC-mediated HNF4A ubiquitination protection against ritonavir-induced hepatotoxicity.
Mol Pharmacol
February 2025
Department of Pharmacology, School of Basic Medical Sciences, Open and Key Laboratory for Pharmacogenomics at Henan Universities, Zhengzhou University, Zhengzhou, China. Electronic address:
Ritonavir (RTV) is an important drug for anti-human immunodeficiency virus treatment and is mainly metabolized by cytochrome P450 (CYP) 3A4. Clinically, the most common side effect of RTV treatment is hepatoxicity. We previously showed that the long noncoding RNA hepatocyte nuclear factor 4 alpha (HNF4A) antisense 1 (HNF4A-AS1) negatively regulated CYP3A4 expression and participated in RTV-induced hepatotoxicity in vitro, but the mechanism has not been well understood.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!