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Systems Approaches to Diabetic Complications

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 20 August 2026 | Viewed by 645

Special Issue Editor


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Guest Editor
Department of Precision and Regenerative Medicine and Ionian Area, University of Bari Aldo Moro, Piazza Giulio Cesare n. 11, 70124 Bari, Italy
Interests: genomics; transcriptomics; diabetic nephropathy; kidney transplantation
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Special Issue Information

Dear Colleagues,

Diabetes and its complications, including microvascular (retinopathy, nephropathy, neuropathy) and macrovascular (cardiovascular disease, stroke, peripheral artery disease), represent complex, multifactorial challenges across molecular, cellular, and systemic levels. This Special Issue invites multidisciplinary contributions deploying system-level approaches to explore the complex interactions driving the onset and progression of these complications. We welcome submissions that incorporate omics technologies (genomics, transcriptomics, proteomics, metabolomics and pathomics), advanced cellular and animal models, computational modeling, and cutting-edge tools such as machine learning and artificial intelligence. These approaches can help elucidate the molecular networks connecting hyperglycemia, inflammation, endothelial dysfunction, fibrosis, and metabolic imbalance to disease pathogenesis and treatment response.

Original research, reviews, and commentaries focused on mechanistic insights, biomarker discovery, and translational applications are encouraged. We particularly value studies that bridge high-throughput data with experimental or clinical validation, supporting precision medicine in diabetic complications.

I am pleased to invite you to participate to this Special Issue.

Dr. Paola Pontrelli
Guest Editor

Manuscript Submission Information

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Keywords

  • diabetes
  • diabetic complications
  • molecular mechanisms
  • precision medicine

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Published Papers (1 paper)

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Research

21 pages, 5841 KB  
Article
Upregulation of Parathyroid Hormone Receptor 1 (PTH1R) in Non-Mechanostimulated Osteocytes Under High-Glucose Conditions Promotes a Macrophage Pro-Inflammatory and Osteoclastogenic Phenotype via IL-6 Secretion
by Irene Tirado-Cabrera, Joan Pizarro-Gomez, Eduardo Martin-Guerrero, Celia Méndez-Rodríguez, Teresita Bellido, Arancha R. Gortazar and Juan A. Ardura
Int. J. Mol. Sci. 2026, 27(4), 1677; https://doi.org/10.3390/ijms27041677 - 9 Feb 2026
Viewed by 375
Abstract
Diabetes mellitus disrupts bone homeostasis, inducing bone fragility, through mechanisms involving chronic inflammation and altered cellular signaling. Osteocytes, the primary mechanosensory cells in bone, play a pivotal role in regulating bone remodeling via the secretion of factors that influence both osteoclast and osteoblast [...] Read more.
Diabetes mellitus disrupts bone homeostasis, inducing bone fragility, through mechanisms involving chronic inflammation and altered cellular signaling. Osteocytes, the primary mechanosensory cells in bone, play a pivotal role in regulating bone remodeling via the secretion of factors that influence both osteoclast and osteoblast activity. We investigated the impact of high glucose on osteocytic parathyroid hormone receptor type 1 (PTH1R) expression and its downstream effects on interleukin-6 (IL-6) secretion, macrophage polarization, and osteoclastogenesis. Using both in vitro and ex vivo bone models, we demonstrate that elevated glucose levels in static conditions without mechanical stimulation induce the overexpression of PTH1R in osteocytes. PTH1R upregulation in turn enhances osteocytic IL-6 secretion associated with the promotion of a pro-inflammatory macrophage M1 phenotype (increased tumor necrosis factor (TNF)-α/CD206 and inducible nitric oxide synthase (iNOS)/CD206 ratios) and the upregulation of the pro-osteoclastogenic markers tartrate-resistant acid phosphatase (TRAP) and receptor activator of nuclear factor kappa-Β (RANK). Neutralization of IL-6 in the osteocytic secretome attenuated macrophage inflammatory gene overexpression, underscoring IL-6’s critical role in this regulatory axis. Our findings reveal that a high-glucose environment triggers osteocytic dysregulation of PTH1R-mediated signaling pathways, amplifying inflammatory and osteoclastogenic activity in bone via IL-6. This osteocyte–macrophage crosstalk may contribute to the increased bone resorption and impaired regeneration observed in diabetic bone disease. Targeting PTH1R upregulation and the IL-6 signaling pathway in osteocytes could represent a novel therapeutic approach to mitigating bone complications associated with diabetes. Full article
(This article belongs to the Special Issue Systems Approaches to Diabetic Complications)
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