Chen Shuqing, Wang Yongqian, Yang Yubin, Xiang Ting, Liu Jiahui, Zhou Houming, Wu Xinlin
Department of Traditional Chinese Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
Department of Musculoskeletal Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
Biomed Res Int. 2017;2017:3524307. doi: 10.1155/2017/3524307. Epub 2017 Mar 2.
Osteoporosis is a common disease causing fracture in older populations. Abnormal apoptosis of osteoblasts contributes to the genesis of osteoporosis. Inhibiting apoptosis of osteoblasts provides a promising strategy to prevent osteoporosis. The proliferation of osteoblasts isolated from osteoporotic patients or healthy subjects was determined by MTT assay. Apoptosis was determined by Annexin V/PI assay. Protein expression was measured by western blot. The proliferation of osteoblasts isolated from osteoporotic patients was inhibited and the apoptosis level of these cells was higher than the osteoblasts from healthy subjects. Incubation with psoralen or estradiol significantly enhanced the proliferation and decreased the apoptosis level of osteoporotic osteoblasts. Western blot demonstrated that psoralen or estradiol treatment downregulated the expression of IRE1, p-ASK, p-JNK, and Bax. Meanwhile, expression of Bcl-2 was upregulated. Pretreatment by IRE1 agonist tunicamycin or JNK agonist anisomycin attenuated the effect of psoralen on osteoporotic osteoblasts. Psoralen inhibited apoptosis of osteoporotic osteoblasts by regulating IRE1-ASK1-JNK pathway.
骨质疏松症是一种在老年人群中导致骨折的常见疾病。成骨细胞的异常凋亡促成了骨质疏松症的发生。抑制成骨细胞凋亡为预防骨质疏松症提供了一种有前景的策略。通过MTT法测定从骨质疏松症患者或健康受试者分离出的成骨细胞的增殖情况。通过Annexin V/PI法测定细胞凋亡情况。通过蛋白质印迹法检测蛋白质表达。从骨质疏松症患者分离出的成骨细胞的增殖受到抑制,且这些细胞的凋亡水平高于来自健康受试者的成骨细胞。用补骨脂素或雌二醇孵育可显著增强骨质疏松症成骨细胞的增殖并降低其凋亡水平。蛋白质印迹显示,补骨脂素或雌二醇处理下调了IRE1、p-ASK、p-JNK和Bax的表达。同时,Bcl-2的表达上调。用IRE1激动剂衣霉素或JNK激动剂茴香霉素预处理可减弱补骨脂素对骨质疏松症成骨细胞的作用。补骨脂素通过调节IRE1-ASK1-JNK通路抑制骨质疏松症成骨细胞的凋亡。