Wang Da, Zhang Hongyu, Cao Xiangheng, Li Dongning, Qiu Ruiyang, Zhao Mengge
College of Food Science and Engineering, Northwest A&F University, Xianyang, Shaanxi, China.
J Food Sci. 2025 Aug;90(8):e70450. doi: 10.1111/1750-3841.70450.
Long-term glucocorticoid therapy is known to induce osteoporosis by disrupting bone metabolism and altering gut microbiota. In this study, C57BL/6J mice were used to establish a glucocorticoid-induced osteoporosis (GIOP) model by intramuscular injection of dexamethasone. The mice were then divided into control, GIOP, and experimental groups; the experimental group was orally administered selenium-enriched egg white protein (Se-EWP) in order to evaluate its bone-protective effects and potential mechanisms. The results showed that Se-EWP significantly improved bone strength, trabecular microstructure, and bone mineral density in GIOP mice; enhanced the expression of bone synthesis-related proteins, such as osterix and osteocalcin; and decreased the expression of bone catabolism-related proteins, such as tartrate-resistant acid phosphatase, receptor activator of nuclear factor-κB ligand, and cathepsin K. In addition, Se-EWP was found to alleviate glucocorticoid-induced gut microflora dysbiosis by increasing beneficial bacteria and microbial diversity. Se-EWP significantly modulated the 5-hydroxytryptamine receptor 1B (Htr1b) pathway, which is crucial for bone homeostasis and gut-bone communication. The modulation of the Htr1b pathway suggests that Se-EWP may exert its anti-osteoporotic effects through this mechanism. These effects were statistically significant (p < 0.05). Correlation analysis revealed significant associations between changes in the intestinal microbiota and bone metabolism parameters, further supporting the hypothesis that Se-EWP exerts its effects through the gut-bone axis. This suggests a novel therapeutic mechanism of action for Se-EWP through the gut-bone axis. In conclusion, this study provides strong evidence supporting the application of Se-EWP in the prevention and treatment of GIOP.
长期糖皮质激素治疗会通过破坏骨代谢和改变肠道微生物群来诱发骨质疏松症。在本研究中，使用C57BL/6J小鼠通过肌肉注射地塞米松建立糖皮质激素诱导的骨质疏松症（GIOP）模型。然后将小鼠分为对照组、GIOP组和实验组；对实验组口服富硒蛋清蛋白（Se-EWP），以评估其对骨骼的保护作用和潜在机制。结果表明，Se-EWP显著改善了GIOP小鼠的骨强度、小梁微观结构和骨密度；增强了骨合成相关蛋白（如osterix和骨钙素）的表达；并降低了骨分解代谢相关蛋白（如抗酒石酸酸性磷酸酶、核因子κB受体激活剂配体和组织蛋白酶K）的表达。此外，发现Se-EWP通过增加有益细菌和微生物多样性来减轻糖皮质激素诱导的肠道微生物群失调。Se-EWP显著调节5-羟色胺受体1B（Htr1b）途径，该途径对骨稳态和肠-骨通讯至关重要。对Htr1b途径的调节表明，Se-EWP可能通过该机制发挥其抗骨质疏松作用。这些效应具有统计学意义（p < 0.05）。相关性分析揭示了肠道微生物群变化与骨代谢参数之间存在显著关联，进一步支持了Se-EWP通过肠-骨轴发挥作用的假设。这表明Se-EWP通过肠-骨轴有了一种新的治疗作用机制。总之，本研究提供了有力证据支持Se-EWP在GIOP预防和治疗中的应用。
