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Rescuing mitochondrial dysfunction in macrophages prevents osteonecrosis of the jaw in anti-resorptive therapy

GSE306512 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2026/03/04 Platform GPL24247
Summary
Mitochondria-driven macrophage dysregulation plays a crucial role in the progression of various inflammatory diseases, yet its exact mechanism in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw (BRONJ) remains poorly understood. Here, we demonstrate that zoledronic acid (ZA) impairs mitochondrial bioenergetic function in macrophages, resulting in elevated mitochondrial membrane potential, accumulated mitochondrial reactive oxygen species, and increased expression of HIF-1α, which subsequently promotes a pro-inflammatory transition in macrophages. Importantly, ZA inhibits autophagy-initiating complex via activation of the TLR4-MyD88/PI3K-AKT-mTOR pathway, thereby impeding clearance of dysfunctional mitochondria to sustain superoxide production.
Published in
Rescuing Mitochondrial Dysfunction in Macrophages Prevents Osteonecrosis of the Jaw in Anti-Resorptive Therapy
Zhang H, Shen X, Liu H et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2026 · PMID 41354629 · doi:10.1002/advs.202517586
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Also filed as BioProject PRJNA1311016 and SRA study SRP612753. Searching any of these in the dataset finder brings you back here.

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