Introduction: Bone morphogenetic proteins (BMPs) are used as key therapeutic agents for the treatment of difficult fractures. While their effects on osteoprogenitors are known, little is known about their effects on the immune system.
Methods: We used permutations of BMP-6 (B), vascular endothelial growth factor (V), and Hedgehog signaling pathway activator smoothened agonist (S), to treat a rat mandibular defect and investigated healing outcomes at week 8, in correlation with the cellular landscape of the immune cells in the fracture callus at week 2.
Results: Maximum recruitment of immune cells to the fracture callus is known to occur at week 2. While the control, S, V, and VS groups remained as nonunions at week 8; all BMP-6 containing groups - B, BV, BS and BVS, showed near-complete to complete healing. This healing pattern was strongly associated with significantly higher ratios of CD4 T (CD45CD3CD4) to putative CD8 T cells (CD45CD3CD4), in groups treated with any permutation of BMP-6. Although, the numbers of putative M1 macrophages (CD45CD3CD11b/cCD38) were significantly lower in BMP-6 containing groups in comparison with S and VS groups, percentages of putative - Th1 cells or M1 macrophages (CD45CD4IFN-γ) and putative - NK, NKT or cytotoxic CD8T cells (CD45CD4IFN-γ) were similar in control and all treatment groups. Further interrogation revealed that the BMP-6 treatment promoted type 2 immune response by significantly increasing the numbers of CD45CD3CD11b/cCD38 putative M2 macrophages, putative - Th2 cells or M2 macrophages (CD45CD4IL-4) cells and putative - mast cells, eosinophils or basophils (CD45CD4IL-4 cells). CD45 non-haematopoietic fractions of cells which encompass all known osteoprogenitor stem cells populations, were similar in control and treatment groups.
Discussion: This study uncovers previously unidentified regulatory functions of BMP-6 and shows that BMP-6 enhances fracture healing by not only acting on osteoprogenitor stem cells but also by promoting type 2 immune response.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9950738 | PMC |
| http://dx.doi.org/10.3389/fimmu.2023.1064238 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Supervised analysis of alternative polyadenylation from single-cell and spatial transcriptomics data with spvAPA.
Brief Bioinform
November 2024
Cancer Institute, Suzhou Medical College, Soochow University, NO. 199 Ren-ai Road, SIP, Suzhou 215000, China.
Alternative polyadenylation (APA) is an important driver of transcriptome diversity that generates messenger RNA isoforms with distinct 3' ends. The rapid development of single-cell and spatial transcriptomic technologies opened up new opportunities for exploring APA data to discover hidden cell subpopulations invisible in conventional gene expression analysis. However, conventional gene-level analysis tools are not fully applicable to APA data, and commonly used unsupervised dimensionality reduction methods often disregard experimentally derived annotations such as cell type identities.
View Article and Find Full Text PDFSpecific recognition mechanism of an antibody to sulfated tyrosine and its potential use in biological research.
J Biol Chem
January 2025
Department of Bioengineering, School of Engineering, The University of Tokyo; Institute of Medical Science, The University of Tokyo; Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo; Medical Device Development and Regulation Research Center, School of Engineering, The University of Tokyo, Japan. Electronic address:
Post-translational modification of proteins is a crucial biological reaction that regulates protein functions by altering molecular properties. The specific detection of such modifications in proteins has made significant contributions to molecular biology research and holds potential for future drug development applications. In HIV research, for example, tyrosine sulfation at the N-terminus of C-C chemokine receptor type 5 (CCR5) is considered to significantly enhance HIV infection efficiency.
View Article and Find Full Text PDFAdvancement in synthetic gene circuits engineering: An alternative strategy for microRNA imaging and disease theranostics.
Biotechnol Adv
January 2025
Department of Urology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China; Institute of Medical Engineering, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an 710061, China; Xianyang Key Laboratory of Molecular Imaging and Drug Synthesis, School of Pharmacy, Shaanxi University of International Trade & Commerce, Xianyang 712046, China. Electronic address:
Gene circuits, which are genetically engineered systems designed to regulate gene expression, are emerging as powerful tools in disease theranostics, especially in mammalian cells. This review explores the latest advances in the design and application of gene circuits for detecting and treating various diseases. Synthetic gene circuits, inspired by electronic systems, offer precise control over therapeutic gene activity, allowing for real-time, user-defined responses to pathological signals.
View Article and Find Full Text PDFDiverse strategies utilized by coronaviruses to evade antiviral responses and suppress pyroptosis.
Int J Biol Macromol
January 2025
Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, China; Institute of Preventive Veterinary Medicine, Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine, Zhejiang University, Hangzhou, China; Key Laboratory of Animal Virology of Ministry of Agriculture, Center for Veterinary Sciences, Zhejiang University, Hangzhou, China; Hainan Institute of Zhejiang University, Sanya, China; Zhejiang University-Xinchang Joint Innovation Centre (TianMu Laboratory), Gaochuang Hi-Tech Park, Xinchang, China. Electronic address:
Viral infections trigger inflammasome-mediated caspase-1 activation. Nevertheless, limited understanding exists regarding how viruses use the active caspase-1 to evade host immune response. Here, we use porcine epidemic diarrhea virus (PEDV) as a model of coronaviruses (CoVs) to illustrate the intricate regulation of CoVs to combat IFN-I signaling and pyroptosis.
View Article and Find Full Text PDFMolecular insights into Parkinson's disease and type 2 diabetes mellitus: Metformin's role and genetic pathways explored.
Exp Neurol
January 2025
Institute for Brain Sciences Research, Center for Translational Neurourology, Huaihe Hospital of Henan University, School of Life Sciences, Henan University, Kaifeng 475004, China. Electronic address:
Article Synopsis
- The study investigates the potential bidirectional relationship between Parkinson's disease (PD) and type 2 diabetes mellitus (T2DM), analyzing shared genetic mechanisms and verifying specific genes involved in the conditions.
- Using Mendelian randomization, researchers found a positive correlation between PD and T2DM, identifying hub genes that are up-regulated in an animal model, which may indicate shared pathogenic processes.
- The research highlights metformin's potential role in treating PD aggravated by T2DM by targeting specific genes and pathways related to inflammation and oxidative stress, with molecular docking analysis confirming the stability of metformin's interaction with key proteins.
Want 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!