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Osteoporosis is a common disease characterized by reduced bone mass, microstructural deterioration, fragility and consequent fragility fractures and is particularly prevalent among the elderly population. Although glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have positive effects on bones, their role in the prevention of osteoporotic fractures remains to be elucidated. The present study assigned female Sprague Dawley rats with osteoporotic fractures into variectomized osteoporosis (OVX), OVX + liraglutide (LIRA) (50 µg/kg/day subcutaneous LIRA) and control groups. At 3 and 6 weeks postoperatively, X-ray, tartrate-resistant acid phosphatase (TRAP) staining, histological and biomechanical assays and assessment of femoral bone mineral density (BMD) were performed. Compared with the OVX group, GLP-1 RA treatment improved the formation of calluses and osseous union. TRAP staining showed significantly fewer osteoclasts in the OVX + LIRA group compared with the OVX group. In the osteoporotically fractured rats, LIRA improved bone strength at the femoral diaphysis, stiffness, ultimate load and femoral trabecular BMD Compared with the OVX group. GLP-1 RA treatment inhibited osteoclast formation and improved trabecular bone architecture and mass in osteoporotic fracture model rats, leading to improved biomechanical strength. GLP-1 RAs may be used as novel anti-osteoporotic fracture agents. [ABSTRACT FROM AUTHOR]

Severe trauma can lead to numerous serious complications, threating the well-being and vitality of the afflicted. The quantity and functionality of PMNs undergo rapid transformations in response to severe trauma, playing a pivotal role in the trauma response. The absence of CCAAT/enhancer-binding protein ε (C/EBPε) profoundly impairs the functionality of polymorphonuclear neutrophils (PMNs), a function of paramount importance in trauma. In this study, by generating mice with C/EBPε knocked out or overexpressed, we substantiate that C/EBPε ensures the restoration of PMN function, enhancing the expression of antimicrobial proteins and thereby promoting trauma recovery. Furthermore, diminished expression of C/EBPε is observed in trauma patients, with levels displaying a negative correlation with ISS and APACHE II scores, suggesting its potential as a prognostic indicator for clinical treatment. Mechanistically, we uncover the upregulation of SIRT1 and the inhibition of P300 participating in the suppression of C/EBPε acetylation, consequently reducing the resilience of mice to trauma. As therapeutic interventions, whether through the sole administration of PMN, NAM treatment, or their combination, all result in an increased survival rate in traumatic mice. In conclusion, our study elucidates the role of C/EBPε in enhancing the resilience to trauma and identifies C/EBPε acetylation as a critical regulatory mechanism, offering potential therapeutic approaches involving PMN transfusion and NAM treatment., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)