Quercetin suppresses ovariectomy-induced osteoporosis in rat mandibles by regulating autophagy and the NLRP3 pathway.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
ACS Applied Bio Materials Pub Date : 2023-12-01 Epub Date: 2024-01-19 DOI:10.1177/15353702231211977
Yue Xiong, Cheng-Wei Huang, Chao Shi, Liang Peng, Yu-Ting Cheng, Wei Hong, Jian Liao
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Abstract

With the aging population and the popularity of implant prostheses, an increasing number of postmenopausal osteoporosis (PMOP) patients require implant restorations; however, poor bone condition affects the long-term stability of implant prostheses. This study aimed to investigate the therapeutic effect of quercetin (QR) compared with alendronate (ALN), the primary treatment for PMOP, on mandibular osteoporosis (OP) induced by ovariectomy (OVX) in female rats. Adult female rats were treated with QR (50 mg/kg/day), ALN (6.25 mg/kg/week) by gavage for 8 weeks, chloroquine (CQ, 10 mg/kg/twice a week), and cytokine release inhibitory drug 3 (MCC950, 10 mg/kg/three times a week) by intraperitoneal injection for 8 weeks after bilateral OVX. Blood samples were collected prior to euthanasia; the mandibles were harvested and subjected to micro-computed tomography (micro-CT) and pathological analysis. QR administration controlled weight gain and significantly improved the bone microstructure in OVX rats, increasing bone mass, and bone mineral density (BMD), reducing bone trabecular spacing, and decreasing osteoclast numbers. Western blotting, real-time quantitative PCR (RT-qPCR), and serum markers confirmed that QR inhibited interleukin- 1β (IL-1β) and interleukin-18 (IL-18) on the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) protein 3 (NLRP3) pathway thereby inhibiting osteoclast differentiation, immunofluorescence and western blotting also confirmed that QR inhibited autophagy in OVX rats and suppressed the number of tartrate-resistant acid phosphatase (TRAP)-stained positive osteoclasts. The findings suggest that QR may protect the bone structure and prevent bone loss in osteoporotic rats by inhibiting the NLRP3 pathway and autophagy in osteoclasts with comparable effects to ALN, thus QR may have the potential to be a promising alternative supplement for the preventive and therapeutic treatment of PMOP.

槲皮素通过调节自噬和NLRP3通路抑制卵巢切除术诱发的大鼠下颌骨骨质疏松症
随着人口老龄化和种植修复体的普及,越来越多的绝经后骨质疏松症(PMOP)患者需要进行种植修复;然而,骨质状况不佳会影响种植修复体的长期稳定性。本研究旨在探讨槲皮素(QR)与阿仑膦酸钠(ALN)(PMOP 的主要治疗药物)相比,对卵巢切除术(OVX)诱导的雌性大鼠下颌骨骨质疏松症(OP)的治疗效果。成年雌性大鼠在双侧卵巢切除术后接受QR(50毫克/千克/天)、ALN(6.25毫克/千克/周)灌胃治疗8周,氯喹(CQ,10毫克/千克/每周两次)和细胞因子释放抑制药物3(MCC950,10毫克/千克/每周三次)腹腔注射治疗8周。安乐死前采集血液样本;收获下颌骨并进行显微计算机断层扫描(micro-CT)和病理分析。服用QR可控制OVX大鼠的体重增加,并显著改善其骨骼微观结构,增加骨量和骨矿物质密度(BMD),缩小骨小梁间距,减少破骨细胞数量。Western印迹、实时定量 PCR(RT-qPCR)和血清标记证实,QR 可抑制核苷酸结合寡聚域(NOD)样受体(NLR)蛋白 3(NLRP3)通路上的白细胞介素 1β (IL-1β)和白细胞介素 18(IL-18),从而抑制破骨细胞分化、免疫荧光和免疫印迹还证实,QR 可抑制 OVX 大鼠的自噬,并抑制抗酒石酸磷酸酶(TRAP)染色阳性破骨细胞的数量。研究结果表明,QR可通过抑制破骨细胞的NLRP3通路和自噬作用来保护骨质疏松症大鼠的骨结构并防止骨质流失,其效果与ALN相当,因此QR有可能成为预防和治疗PMOP的一种有前途的替代性补充剂。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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