Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
PeerJ. 2023 Oct 16;11:e16121. doi: 10.7717/peerj.16121. eCollection 2023.
Postmenopausal osteoporosis and osteoporosis-related fractures are world-wide serious public health problem. Recent studies demonstrated that inhibiting caveolin-1 leads to osteoclastogenesis suppression and protection against OVX-induced osteoporosis. This study aimed to explore the mechanism of caveolin-1 mediating bone loss and the potential therapeutic target.
Thirty C57BL/6 female mice were allocated randomly into three groups: sham or bilateral ovariectomy (OVX) surgeries were performed for mice and subsequently daidzein or vehicle was administrated to animals (control, OVX + vehicle and OVX + daidzein). After 8-week administration, femurs were harvested for Micro-CT scan, histological staining including H&E, immunohistochemistry, immunofluorescence, TRAP. Bone marrow endothelial cells (BMECs) were cultured and treated with inhibitors of caveolin-1 (daidzein) or EGFR (erlotinib) and then scratch wound healing and ki67 assays were performed. In addition, cells were harvested for western blot and PCR analysis.
Micro-CT showed inhibiting caveolin-1with daidzein alleviated OVX-induced osteoporosis and osteogenesis suppression. Further investigations revealed H-type vessels in cancellous bone were decreased in OVX-induced mice, which can be alleviated by daidzein. It was subsequently proved that daidzein improved migration and proliferation of BMECs hence improved H-type vessels formation through inhibiting caveolin-1, which suppressed EGFR/AKT/PI3K signaling in BMECs.
This study demonstrated that daidzein alleviates OVX-induced osteoporosis by promoting H-type vessels formation in cancellous bone, which then promotes bone formation. Activating EGFR/AKT/PI3K signaling could be the critical reason.
绝经后骨质疏松症和与骨质疏松症相关的骨折是全球性严重的公共卫生问题。最近的研究表明，抑制窖蛋白-1 可抑制破骨细胞生成并预防去卵巢诱导的骨质疏松症。本研究旨在探讨窖蛋白-1 介导骨丢失的机制和潜在的治疗靶点。
30 只 C57BL/6 雌性小鼠随机分为 3 组：假手术或双侧卵巢切除术（OVX）后给予大豆苷元或载体（对照组、OVX+载体和 OVX+大豆苷元）。给药 8 周后，采集股骨进行 Micro-CT 扫描、H&E 染色、免疫组织化学、免疫荧光、TRAP 染色。培养骨髓内皮细胞（BMEC），用窖蛋白-1（大豆苷元）或 EGFR（厄洛替尼）抑制剂处理，然后进行划痕愈合和 ki67 检测。此外，还采集细胞进行 Western blot 和 PCR 分析。
Micro-CT 显示，用大豆苷元抑制窖蛋白-1 可缓解 OVX 诱导的骨质疏松症和成骨抑制。进一步研究表明，OVX 诱导的小鼠松质骨中的 H 型血管减少，大豆苷元可缓解这种减少。随后证明，大豆苷元通过抑制窖蛋白-1 改善 BMEC 的迁移和增殖，从而改善 H 型血管形成，从而激活 EGFR/AKT/PI3K 信号通路在 BMECs 中。
本研究表明，大豆苷元通过促进松质骨中 H 型血管形成来缓解 OVX 诱导的骨质疏松症，从而促进骨形成。激活 EGFR/AKT/PI3K 信号通路可能是关键原因。
