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

Autor: Florencio-Silva R; Universidade Federal de São Paulo - UNIFESP, Escola Paulista de Medicina - EPM, Departamento de Ginecologia, São Paulo, SP, Brazil; Universidade Federal de São Paulo - UNIFESP, Escola Paulista de Medicina - EPM, Departamento de Morfologia e Genética, Disciplina de Histologia e Biologia Estrutural, São Paulo, SP, Brazil. Electronic address: silva05@unifesp.br., Sasso GRDS; Universidade Federal de São Paulo - UNIFESP, Escola Paulista de Medicina - EPM, Departamento de Morfologia e Genética, Disciplina de Histologia e Biologia Estrutural, São Paulo, SP, Brazil., Sasso-Cerri E; São Paulo State University (UNESP), School of Dentistry, Araraquara - Department of Morphology, Genetics, Orthodontics and Pediatric Dentistry - Laboratory of Histology and Embryology, Araraquara, SP, Brazil., Cerri PS; São Paulo State University (UNESP), School of Dentistry, Araraquara - Department of Morphology, Genetics, Orthodontics and Pediatric Dentistry - Laboratory of Histology and Embryology, Araraquara, SP, Brazil., Gil CD; Universidade Federal de São Paulo - UNIFESP, Escola Paulista de Medicina - EPM, Departamento de Morfologia e Genética, Disciplina de Histologia e Biologia Estrutural, São Paulo, SP, Brazil., de Jesus Simões M; Universidade Federal de São Paulo - UNIFESP, Escola Paulista de Medicina - EPM, Departamento de Ginecologia, São Paulo, SP, Brazil; Universidade Federal de São Paulo - UNIFESP, Escola Paulista de Medicina - EPM, Departamento de Morfologia e Genética, Disciplina de Histologia e Biologia Estrutural, São Paulo, SP, Brazil.
Jazyk: angličtina
Zdroj: Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft [Ann Anat] 2025 Jan; Vol. 257, pp. 152318. Date of Electronic Publication: 2024 Aug 30.
DOI: 10.1016/j.aanat.2024.152318
Abstrakt: Background: 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.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier GmbH. All rights reserved.)
Databáze: MEDLINE
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