Relationship between autophagy and NLRP3 inflammasome during articular cartilage degradation in oestrogen-deficient rats with streptozotocin-induced diabetes

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Autor(es): dc.contributorUniversidade Federal de São Paulo (UNIFESP)-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.creatorFlorencio-Silva, Rinaldo-
Autor(es): dc.creatorSasso, Gisela Rodrigues da Silva-
Autor(es): dc.creatorSasso-Cerri, Estela-
Autor(es): dc.creatorCerri, Paulo Sérgio-
Autor(es): dc.creatorGil, Cristiane Damas-
Autor(es): dc.creatorde Jesus Simões, Manuel-
Data de aceite: dc.date.accessioned2025-08-21T21:36:27Z-
Data de disponibilização: dc.date.available2025-08-21T21:36:27Z-
Data de envio: dc.date.issued2025-04-29-
Data de envio: dc.date.issued2024-12-31-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1016/j.aanat.2024.152318-
Fonte completa do material: dc.identifierhttps://hdl.handle.net/11449/302035-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/302035-
Descrição: dc.descriptionBackground: Estrogen deficiency and Diabetes mellitus (DM) cause joint tissue deterioration, although the mechanisms are uncertain. This study evaluated the immunoexpression of autophagy and NLRP3-inflammasome markers, in rat articular cartilage with estrogen deficiency and DM. Methods: Twenty rats were sham-operated (SHAM) or ovariectomized (OVX) and equally allocated into four groups: SHAM and OVX groups administered with vehicle solution; SHAM and OVX groups treated with 60 mg/kg/body weight of streptozotocin, intraperitoneally, to induce DM (SHAM-DM and OVX-DM groups). After seven weeks, the rats were euthanized, and their joint knees were processed for paraffin embedding. Sections were stained with haematoxylin-eosin, toluidine blue, safranin-O/fast-green or subjected to picrosirius-red-polarisation method; immunohistochemistry to detect beclin-1 and microtubule-associated protein 1B-light chain 3 (autophagy markers), NLRP3 and interleukin-1β (IL-1β) (inflammasome activation markers), along with matrix metalloproteinase-9 (MMP-9), Nuclear factor-kappa B (NFκB), and Vascular endothelial growth factor A (VEGF-A) were performed. Results: Deterioration of articular cartilage and subchondral bone were greater in SHAM-DM and OVX-DM groups. Higher percentages of immunolabeled chondrocytes to NLRP3, IL-1β, MMP-9, NFκB, and VEGF-A, as well as lower percentages of chondrocytes immunolabeled to autophagy markers, were noticed in estrogen-deficient and diabetic groups. These differences were greater in the OVX-DM group. Percentages of immunolabeled chondrocytes showed negative correlation between autophagy markers v.s IL-1β, NLRP-3, MMP-9, NFκB, and VEGF-A, along with positive correlation between VEGF-A vs. MMP-9, NFκB, IL-1β, and NLRP3, and MMP-9 vs. NFκB. Conclusions: In conclusion, autophagy reduction and NLRP3 inflammasome activation in chondrocytes may be implicated in articular cartilage degradation, under estrogen-deficient and DM conditions. Moreover, the combination of estrogen deficiency and DM may potentiate those effects.-
Descrição: dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-
Descrição: dc.descriptionUniversidade Federal de São Paulo - UNIFESP Escola Paulista de Medicina - EPM Departamento de Ginecologia, SP-
Descrição: dc.descriptionUniversidade Federal de São Paulo - UNIFESP Escola Paulista de Medicina - EPM Departamento de Morfologia e Genética Disciplina de Histologia e Biologia Estrutural, SP-
Descrição: dc.descriptionSão Paulo State University (UNESP) School of Dentistry Araraquara - Department of Morphology Genetics Orthodontics and Pediatric Dentistry - Laboratory of Histology and Embryology, SP-
Descrição: dc.descriptionSão Paulo State University (UNESP) School of Dentistry Araraquara - Department of Morphology Genetics Orthodontics and Pediatric Dentistry - Laboratory of Histology and Embryology, SP-
Descrição: dc.descriptionFAPESP: 2020/03565-2-
Descrição: dc.descriptionFAPESP: 2022/02327-6-
Idioma: dc.languageen-
Relação: dc.relationAnnals of Anatomy-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectArticular cartilage-
Palavras-chave: dc.subjectAutophagy-
Palavras-chave: dc.subjectDiabetes mellitus-
Palavras-chave: dc.subjectEstrogen deficiency-
Palavras-chave: dc.subjectNLRP3-inflammasome-
Título: dc.titleRelationship between autophagy and NLRP3 inflammasome during articular cartilage degradation in oestrogen-deficient rats with streptozotocin-induced diabetes-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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