Possible role of annexin A1/FPR2 pathway in COX2/NLRP3 inflammasome regulation in alveolar bone cells of estrogen-deficient female rats with diabetes mellitus

Autor(es)

Sasso, Gisela Rodrigues Da Silva ; Cerri, Paulo Sergio ; Sasso-Cerri, Estela ; Simoes, Manuel Jesus ; Gil, Cristiane Damas ; Florencio-Silva, Rinaldo

• Tipo de documento: Artigo Científico
• Fonte: Journal of Periodontology; v. 95, n. 8, p. 15-pg., 2023-11-21.

Resumo

BackgroundAnnexin A1 (ANXA1) and the NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome play important roles in bone remodeling. However, expression profiles of these factors in bone cells under diabetes mellitus (DM) and estrogen-deficient conditions are poorly understood. This study investigated the immunoexpression of ANXA1 and its formyl peptide receptor 2 (FPR2), as well as NLRP3 inflammasome mediators, during remodeling of the alveolar process in diabetic and estrogen-deficient rats.MethodsTwenty adult female Wistar rats were divided into four groups (n = 5): Sham-operated (SHAM) and ovariectomized (OVX) rats received a vehicle solution, and SHAM and OVX rats were intraperitoneally administered 60 mg/kg/body weight (BW) of streptozotocin (STZ) to induce DM (SHAM-Di and OVX-Di groups). After 7 weeks, the rats were euthanized and their maxillae were fixed in phosphate-buffered 4% formaldehyde and embedded in paraffin. Sections were stained with hematoxylin/eosin (H&E) and picrosirius red or subjected to immunohistochemical detection of ANXA1, FPR2, NLRP3, interleukin-1 beta (IL-1 beta), and cyclooxygenase-2 (COX2).ResultsEstrogen deficiency and DM were associated with deleterious effects in bone tissue, as evidenced by a lower number of osteocytes and higher number of empty lacunae in the SHAM-Di and OVX-Di groups compared to the nondiabetic groups. Both diabetic groups showed a smaller vascular area and weaker collagen fiber birefringence intensity in alveolar bone tissue. A significantly higher number of ANXA1/FPR2-positive osteoblasts, osteocytes, and osteoclasts was accompanied by a significantly higher number of these cells immunolabeled for COX2, NLRP3, and IL-1 beta in the diabetic and OVX groups, especially in both estrogen-deficient and diabetic rats.ConclusionThese results indicate a possible role for the ANXA1/FPR2 pathway as a fine-tuning/anti-inflammatory regulator to counterbalance exacerbated COX2/NLRP3/IL-1 beta activation in bone cells during bone remodeling under estrogen deficiency and DM. (AU)

• Processo FAPESP: 20/03565-2 - Efeito da anexina A1 e de seus peptídeos miméticos em modelos de resposta inflamatória in vitro (2D e 3D) e de toxicidade aguda in vivo
• Beneficiário: Cristiane Damas Gil
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 22/02327-6 - Impacto do tratamento farmacológico com o peptídeo mimético da Anexina A1 em modelo experimental da Doença de Parkinson
• Beneficiário: Cristiane Damas Gil
• Modalidade de apoio: Auxílio à Pesquisa - Regular