Department of Orthopedics, YangPu Hospital, TongJi University School of Medicine, Shanghai, 200090, People's Republic of China.
Department of Orthopedics, YangPu Hospital, TongJi University School of Medicine, Shanghai, 200090, People's Republic of China.
J Pharmacol Sci. 2016 Apr;130(4):204-11. doi: 10.1016/j.jphs.2016.02.001. Epub 2016 Feb 8.
Notwithstanding compelling contribution of NF-κB to the progression of osteoporosis has been reported, little is known regarding direct inhibition of NF-κB benefiting osteoporosis. In this study, therefore, we evaluated the role of celastrol, an NF-κB inhibitor, in a mouse model of secondary osteoporosis. Animals were divided into three groups as Sham (control), SO (secondary osteoporosis) and SO + CA (secondary osteoporosis treated with celastrol). Significant decreases in body weight and body fat were observed following celastrol treatment in SO group, but leptin levels were much higher. Celastrol also exhibited a significant decrease in urinary calcium excretion. Moreover, other important events were observed after celastrol treatment, covering substantial decrements in serum concentrations of PTH, TRAP-5b, CTX and DPD, improved structure of articular cartilage and cancellous bone (revealed by H&E and safranin-O staining), and significant decline in levels of NF-κB (P65), MMP-1, and MMP-9. These findings demonstrated that celastrol treatment not only improved abnormal lipid metabolism and hypercalciuria in mice subjected to secondary osteoporosis, but also ameliorated articular cartilage lesions. Our results provided evidence of targeted therapy for NF-κB in the clinical treatment of secondary osteoporosis.
尽管已有研究报道 NF-κB 对骨质疏松症的进展有重要作用，但关于直接抑制 NF-κB 对骨质疏松有益的研究还很少。因此，在本研究中，我们评估了 NF-κB 抑制剂雷公藤红素在继发性骨质疏松症小鼠模型中的作用。动物分为三组：假手术组（对照组）、SO 组（继发性骨质疏松症）和 SO+CA 组（用雷公藤红素治疗的继发性骨质疏松症）。在 SO 组中，用雷公藤红素治疗后，体重和体脂明显下降，但瘦素水平更高。雷公藤红素还显著降低了尿钙排泄。此外，在雷公藤红素治疗后还观察到其他重要事件，包括血清甲状旁腺激素（PTH）、TRAP-5b、CTX 和 DPD 浓度显著降低，关节软骨和松质骨结构改善（通过 H&E 和番红 O 染色显示），NF-κB（P65）、MMP-1 和 MMP-9 水平显著下降。这些发现表明，雷公藤红素治疗不仅改善了继发性骨质疏松症小鼠的异常脂质代谢和高钙尿症，还改善了关节软骨损伤。我们的研究结果为 NF-κB 在继发性骨质疏松症的临床治疗中的靶向治疗提供了证据。
