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

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.

The study findings demonstrated a significant association between C-reactive protein levels and trabecular bone score : NHANES 2005-2008

“…Several potential mechanisms have been proposed to elucidate this association. Elevated CRP levels in the liver can increase the expression of additional in ammatory markers like interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFα [30], Elevated levels of NLRP3 in ammasome expression can enhance bone resorption [30,31]. Moreover, in ammation can upregulate the production of ROS (reactive oxygen species); excessive ROS can diminish the quantity and capacity of osteoblasts, leading to impaired bone formation and eventual bone fragility [32].…”

Onion (Allium cepa L.) Flavonoid Extract Ameliorates Osteoporosis in Rats Facilitating Osteoblast Proliferation and Differentiation in MG-63 Cells and Inhibiting RANKL-Induced Osteoclastogenesis in RAW 264.7 Cells

“…Blood sample was collected from the retro-orbital vein and centrifuged at 1000× g for 15 min at 4 • C to separate serum, and all serum samples were kept at −80 • C. The femurs were isolated as quickly as possible, and tissue was rinsed with phosphate buffer solution (PBS) and fixed in 4% neutral formaldehyde (pH 7.0) for further experiments. Based on previous studies, 50 mg/kg OFE was selected as the medium dose [45][46][47][48], with a half-dose of the medium dose (25 mg/kg) and a 1.5-fold increase in the high dose (75 mg/kg) [49]. And, based on the human dose of alendronate of 10 mg/day, a dose of 1 mg/kg/day was selected for rats.…”