Quercetin alleviates osteoporosis in rat mandibles induced by ovariectomy through modulation of autophagy and inhibition of NLRP3 pathway

Abstract

Abstract Background With the aging population and the popularity of implant prostheses, more and more postmenopausal patients with osteoporosis (PMOP) have a need for implant restorations, but poor bone condition affects the long-term stability of their implant prostheses. The aim of this study was to investigate the therapeutic effect of quercetin (QR) compared to alendronate (ALN), the primary treatment for PMOP, on mandibular OP induced by ovariectomy in female rats (OVA). Methods 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 MCC950 (10 mg/kg/three times a week) by intraperitoneal injection for 8 weeks after bilateral ovariectomy. Blood samples were collected prior to euthanasia; the mandibles were harvested and subjected to MicroCT and pathological analysis. Results The results showed that QR administration controlled weight gain and significantly improved bone microstructure in OVA rats, increasing bone mass, and Bone mineral density (BMD), reducing bone trabecular spacing, and decreasing osteoclast numbers. WB, rt-qPCR, and serum markers confirmed that QR inhibited the differentiation of osteoclasts on the NLRP3 pathway that promotes osteoclast differentiation of IL-1β, IL-18, Immunofluorescence, WB also confirmed that QR inhibited autophagy in OVA rats and suppressed the number of Trap-stained positive osteoclasts. Conclusion QR may protect the skeleton and prevent bone loss in osteoporotic rats by inhibiting the NLRP3 pathway and autophagy in osteoclasts with comparable effects to ALN, thus QR has the potential to be a promising alternative supplement for the preventive and therapeutic treatment of postmenopausal osteoporosis.