Bisphosphonate-related osteonecrosis induced change in alveolar bone architecture in rats with participation of Wnt sign
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ORIGINAL ARTICLE
Bisphosphonate-related osteonecrosis induced change in alveolar bone architecture in rats with participation of Wnt signaling Vanessa Costa de Sousa Ferreira 1,2 & Amanda Pimentel Lopes 1,2 & Nicholas Militão Alves 1,2 & Fatima Regina Nunes Sousa 1 & Karuza Maria Alves Pereira 1,2 & Delane Viana Gondim 1,2 & Vírginia Claúdia Carneiro Girão 1 & Renata Ferreira Carvalho Leitão 1 & Paula Goes 3,2,4 Received: 30 April 2020 / Accepted: 25 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Objective This work aimed to study the role of inflammation in medication-related osteonecrosis of the jaw (MRONJ) in rats with focus on Wnt signaling. Methods A total of 36 female Wistar rats (12 weeks ± 200 g) were divided into 2 groups (n = 6) in 3 experiments: saline (SAL) and zoledronic acid (ZOL). For MRONJ induction, rats received 0.1 mg/kg of ZOL (ip) 3×/week for 9 weeks. Animals from the SAL group received 0.1 mg/kg of 0.9% SAL, ip 3×/week for 9 weeks. On the 8th week, 3 left upper molars were extracted, and on the 11th week, they were euthanized. Maxillae were evaluated by macroscopic and histopathological analyses; scanning electron microscopy (SEM); immunohistochemistry for DKK-1, Wnt 10b, and caspase-3; and Raman spectrometry. Gingiva was also collected for TNF-α e IL-1β quantification. Results Bone necrosis was confirmed by healing impairment, reduced number of viable osteocytes, increased caspase-3 immunoexpression, and increased number of empty lacunae (p < 0.05). ZOL enhanced inflammation and increased gingival levels of IL-1β and TNF-α (p < 0.05). Irregular indentations were seen on bone after ZOL administration. Bone necrosis was marked by reduced amount of total and type I collagen. ZOL reduced the mineral/matrix ratio and increased carbonate/phosphate ratio. It was observed a significant reduction on Wnt10b and beta-catenin immunolabeling in the bone tissue of ZOL group. Conclusion In summary, MRONJ model caused bone necrosis due to intense inflammation. Wnt signaling seems to play an important role in this process. Clinical relevance New therapeutic strategies focusing on Wnt pathway can provide an interesting approach for future treatments. Keywords Osteonecrosis . Bisphosphonates . Zoledronic acid . Bone architecture . Inflammation . Wnt signaling
Introduction Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00784-020-03551-7) contains supplementary material, which is available to authorized users. * Paula Goes [email protected] 1
Department of Morphology, Medical School, Federal University of Ceará, Fortaleza, CE, Brazil
2
Nucleus of Study and Research in Pain, Inflammation and Osteoimmunology (NEPDIO), Medical School, Federal University of Ceará, Fortaleza, CE, Brazil
3
Department of Pathology and Legal Medicine, Medical School, Federal University of Ceará, Fortaleza, CE, Brazil
4
Departamento de Patologia e Medicina Legal, Faculdade de Medicina, Universidade Federal do Ceará, Rua Monsenhor Furtado
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