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Exenatide, a glucagon-like peptide-1 receptor agonist, may negatively impact bone healing in rats: histopathological, biochemical, and in silico findings.    
Yazarlar (9)
Doç. Dr. Fatih UĞUR Doç. Dr. Fatih UĞUR
Kastamonu Üniversitesi, Türkiye
Ibrahim Yilmaz
T.C. Sağlık Bakanlığı,, Türkiye
Ersin Guner
Ankara Numune Education And Research Hospital, Türkiye
Mehmet Albayrak
Istanbul Rumeli University, Türkiye
Dr. Öğr. Üyesi Recep TAŞKİN Dr. Öğr. Üyesi Recep TAŞKİN
Kastamonu Üniversitesi, Türkiye
Dr. Öğr. Üyesi Nurtaç SARIKAŞ Dr. Öğr. Üyesi Nurtaç SARIKAŞ
Kastamonu Üniversitesi, Türkiye
Dr. Öğr. Üyesi Mehmet Akif BİLDİRİCİ Dr. Öğr. Üyesi Mehmet Akif BİLDİRİCİ
Kastamonu Üniversitesi, Türkiye
Dr. Öğr. Üyesi Ayşe Başak DELLALBAŞI Dr. Öğr. Üyesi Ayşe Başak DELLALBAŞI
Kastamonu Üniversitesi, Türkiye
Dr. Öğr. Üyesi Candemir ÖZCAN Dr. Öğr. Üyesi Candemir ÖZCAN
Kastamonu Üniversitesi, Türkiye
Devamını Göster
Özet
This study evaluates the effects of exenatide (EXE), a glucagon-like peptide-1 (GLP-1) receptor agonist, on bone healing in rats using a single radius cortical defect model and histopathological, biochemical, and in silico methods. Forty-two male Sprague-Dawley rats, excluding controls, were divided into 7 groups after receiving a standard radius defect. The serum levels of total protein (TP), calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), osteocalcin (OC), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) in each specimen were measured. Radius samples were examined histopathologically using hematoxylin and eosin (H&E) and Masson's trichrome staining. Molecular docking analyses were used to assess EXE interactions with the GLP-1 receptor and osteogenic transcription factors. Statistical significance was set at p < 0.05. Changes in the selected serum markers were observed in the blood samples obtained from the specimens; however, these changes may not have been due to EXE administration. No significant negative effect on bone healing was observed in the groups that received subcutaneous EXE after the bone defect was created. By contrast, it was observed that for the treatment group that received EXE for 7 consecutive days before the bone defect was created on Day 7, bone healing progressed more slowly than in the groups treated with saline. Regarding the binding of EXE to the other target receptors, root mean square deviation (RMSD) values were low, bruised surface area (BSA) was high, and electrostatic interactions were strong, indicating that the ligand (i.e., EXE) binds to the selected receptor surfaces. Although the data obtained from the in vitro analyses in this study were verified using molecular docking, it should be noted that its design is preclinical. Given the widespread clinical use of GLP-1 receptor agonists in the management of type 2 diabetes mellitus (T2DM), our research findings may have translational relevance. Although derived from an experimental animal model, these results suggest that GLP-1 agonists such as EXE can exert additional effects on bone healing and inflammatory processes, thus warranting further studies, including controlled clinical investigations, to elucidate the potential implications for patient care.
Anahtar Kelimeler
Bone regeneration | Exenatide | GLP-1 receptor agonist | Inflammatory cytokines | Molecular docking
Makale Türü Özgün Makale
Makale Alt Türü Uluslararası alan indekslerindeki dergilerde yayınlanan tam makale
Dergi Adı Journal of orthopaedic surgery and research
Dergi ISSN 1749-799X Wos Dergi Scopus Dergi
Makale Dili İngilizce
Basım Tarihi 10-2025
Cilt No 20
Sayı 1
Sayfalar 883 / 0
Doi Numarası 10.1186/s13018-025-06300-2