Bisphosphonate-related osteonecrosis induced change in alveolar bone architecture in rats with participation of Wnt signaling.

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.

journal_name

Clin Oral Investig

authors

de Sousa Ferreira VC,Lopes AP,Alves NM,Sousa FRN,Pereira KMA,Gondim DV,Girão VCC,Leitão RFC,Goes P

doi

10.1007/s00784-020-03551-7

subject

Has Abstract

pub_date

2021-02-01 00:00:00

pages

673-682

issue

2

eissn

1432-6981

issn

1436-3771

pii

10.1007/s00784-020-03551-7

journal_volume

25

pub_type

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