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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
by
Sarikas, Nurtac
, Taskin, Recep
, Guner, Ersin
, Yilmaz, Ibrahim
, Ozcan, Candemir
, Albayrak, Mehmet
, Dellalbasi, Ayse Basak
, Ugur, Fatih
, Bildirici, Mehmet Akif
in
Animals
/ Bone regeneration
/ Exenatide
/ Exenatide - pharmacology
/ Fracture Healing - drug effects
/ Fracture Healing - physiology
/ GLP-1 receptor agonist
/ Glucagon
/ Glucagon-Like Peptide-1 Receptor - metabolism
/ Glucagon-Like Peptide-1 Receptor Agonists
/ Hypoglycemic Agents - pharmacology
/ Inflammatory cytokines
/ Interleukins
/ Male
/ Medicine
/ Medicine & Public Health
/ Molecular docking
/ Molecular Docking Simulation - methods
/ Orthopedics
/ Peptides - pharmacology
/ Phosphatases
/ Rats
/ Rats, Sprague-Dawley
/ Surgical Orthopedics
/ Tumor necrosis factor
/ Type 2 diabetes
2025
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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
by
Sarikas, Nurtac
, Taskin, Recep
, Guner, Ersin
, Yilmaz, Ibrahim
, Ozcan, Candemir
, Albayrak, Mehmet
, Dellalbasi, Ayse Basak
, Ugur, Fatih
, Bildirici, Mehmet Akif
in
Animals
/ Bone regeneration
/ Exenatide
/ Exenatide - pharmacology
/ Fracture Healing - drug effects
/ Fracture Healing - physiology
/ GLP-1 receptor agonist
/ Glucagon
/ Glucagon-Like Peptide-1 Receptor - metabolism
/ Glucagon-Like Peptide-1 Receptor Agonists
/ Hypoglycemic Agents - pharmacology
/ Inflammatory cytokines
/ Interleukins
/ Male
/ Medicine
/ Medicine & Public Health
/ Molecular docking
/ Molecular Docking Simulation - methods
/ Orthopedics
/ Peptides - pharmacology
/ Phosphatases
/ Rats
/ Rats, Sprague-Dawley
/ Surgical Orthopedics
/ Tumor necrosis factor
/ Type 2 diabetes
2025
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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
by
Sarikas, Nurtac
, Taskin, Recep
, Guner, Ersin
, Yilmaz, Ibrahim
, Ozcan, Candemir
, Albayrak, Mehmet
, Dellalbasi, Ayse Basak
, Ugur, Fatih
, Bildirici, Mehmet Akif
in
Animals
/ Bone regeneration
/ Exenatide
/ Exenatide - pharmacology
/ Fracture Healing - drug effects
/ Fracture Healing - physiology
/ GLP-1 receptor agonist
/ Glucagon
/ Glucagon-Like Peptide-1 Receptor - metabolism
/ Glucagon-Like Peptide-1 Receptor Agonists
/ Hypoglycemic Agents - pharmacology
/ Inflammatory cytokines
/ Interleukins
/ Male
/ Medicine
/ Medicine & Public Health
/ Molecular docking
/ Molecular Docking Simulation - methods
/ Orthopedics
/ Peptides - pharmacology
/ Phosphatases
/ Rats
/ Rats, Sprague-Dawley
/ Surgical Orthopedics
/ Tumor necrosis factor
/ Type 2 diabetes
2025
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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
Journal Article
Exenatide, a glucagon-like peptide-1 receptor agonist, may negatively impact bone healing in rats: histopathological, biochemical, and in silico findings
2025
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Overview
Background
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.
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
2+
), 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.
Results
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.
Conclusion
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.
Publisher
BioMed Central,BioMed Central Ltd,BMC
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