Anti-vascular endothelial growth factor antibody monotherapy causes destructive advanced periodontitis in rice rats (Oryzomys palustris).

Autor: Messer JG; Department of Physiological Sciences, University of Florida (UF), Gainesville, FL, United States of America. Electronic address: jgmesser@ufl.edu., Castillo EJ; Department of Physiological Sciences, University of Florida (UF), Gainesville, FL, United States of America. Electronic address: evelynjcastillo@ufl.edu., Abraham AM; Department of Physiological Sciences, University of Florida (UF), Gainesville, FL, United States of America. Electronic address: abelabra@ufl.edu., Jiron JM; Department of Physiological Sciences, University of Florida (UF), Gainesville, FL, United States of America. Electronic address: jjiron@ufl.edu., Israel R; Department of Physiological Sciences, University of Florida (UF), Gainesville, FL, United States of America. Electronic address: ronniei@ufl.edu., Yarrow JF; Research Service, VA Medical Center, Gainesville, FL, United States of America; Division of Endocrinology, Diabetes, and Metabolism, University of Florida College of Medicine, Gainesville, FL, United States of America. Electronic address: Joshua.yarrow@medicine.ufl.edu., Thomas S; Department of Physiological Sciences, University of Florida (UF), Gainesville, FL, United States of America. Electronic address: sthomas101@ufl.edu., Reynolds MC; Research Service, VA Medical Center, Gainesville, FL, United States of America., Wnek RD; Research Service, VA Medical Center, Gainesville, FL, United States of America., Jorgensen M; Department of Pediatrics, College of Medicine, UF, United States of America. Electronic address: marda@ufl.edu., Wanionok N; Department of Physiological Sciences, University of Florida (UF), Gainesville, FL, United States of America., Van Poznak C; University of Michigan, Ann Arbor, MI, United States of America. Electronic address: cvanpoz@med.umich.edu., Bhattacharyya I; Department of Oral & Maxillofacial Diagnostic Sciences, College of Dentistry, UF, United States of America. Electronic address: IBHATTACHARYYA@dental.ufl.edu., Kimmel DB; Department of Physiological Sciences, University of Florida (UF), Gainesville, FL, United States of America. Electronic address: kimmeldb@comcast.net., Aguirre JI; Department of Physiological Sciences, University of Florida (UF), Gainesville, FL, United States of America. Electronic address: aguirrej@ufl.edu.
Jazyk: angličtina
Zdroj: Bone [Bone] 2020 Jan; Vol. 130, pp. 115141. Date of Electronic Publication: 2019 Nov 07.
DOI: 10.1016/j.bone.2019.115141
Abstrakt: Objective: Angiogenesis inhibitors (AgI) are commonly used in combination chemotherapy protocols to treat cancer, and have been linked to osteonecrosis of the jaw (ONJ). However, it is unknown if AgI therapy alone is sufficient to induce ONJ. We have previously established an ONJ model in rice rats with localized periodontitis that receive zoledronic acid (ZOL). The purpose of this study was to use this model to determine the role of anti-vascular endothelial growth factor A (anti-VEGF) antibody treatment of rice rats with localized maxillary periodontitis. We hypothesized that rice rats with localized maxillary periodontitis given anti-VEGF monotherapy will develop oral lesions that resemble ONJ, defined by exposed, necrotic alveolar bone.
Methods: At age 4 weeks, 45 male rice rats were randomized into three groups (n = 15): 1) VEH (saline), 2) ZOL (80 μg/kg body weight, intravenously once monthly), and 3) anti-VEGF (5 mg B20-4.1.1/kg body weight, subcutaneously twice weekly). After 24 weeks, rats were euthanized, jaws were excised and a high-resolution photograph of each quadrant was taken to assign a severity grade based on gross appearance. Jaws were then fixed, scanned by MicroCT, decalcified and sectioned for histopathologic and immunohistochemical analyses.
Results: 40-80% of the rats in the three groups developed gross oral lesions. 50% of ZOL rats developed ONJ. In contrast, 80% of the anti-VEGF rats developed destructive advanced periodontitis that was characterized by extreme alveolar bone loss and fibrosis. Anti-VEGF rats never developed exposed, necrotic bone. Furthermore, only anti-VEGF rats developed mild to severe mandibular periodontitis. Compared to VEH rats, more T-cells were found in periodontal lesions of anti-VEGF rats and more cells of the monocyte lineage were found in ONJ lesions of ZOL rats.
Conclusions: Anti-VEGF monotherapy administered to a validated rodent model of ONJ caused a destructive advanced form of periodontitis that differed significantly from ONJ.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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