Inductive Effect of Palmatine on Apoptosis in RAW 264.7 Cells.
Inductive Effect of Palmatine on Apoptosis in RAW 264.7 Cells.
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DOI：
10.1155/2016/7262054
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Hisamitsu T
中科院分区：
文献类型：
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作者：
Ishikawa S;Tamaki M;Ogawa Y;Kaneki K;Zhang M;Sunagawa M;Hisamitsu T
骨质疏松症是一种严重的公共健康问题，其特征是骨密度降低和骨微结构恶化。目前的治疗选择要么针对破骨细胞吸收，要么针对成骨细胞形成。据报道，黄连素是巴马汀的结构类似物，在骨质疏松症模型中可以抑制骨丢失。本研究采用破骨细胞骨吸收细胞进行体外骨代谢的观察。我们证明了小鼠破骨前细胞系(RAW 264.7)对巴马汀的敏感性高于小鼠成骨细胞系(MC3T3-E1)，40 μM巴马汀使细胞存活率显著下降。随着巴马汀剂量的增加，NO代谢产物NO_2−水平和NO诱导酶的破骨细胞iNOS mRNA表达也增加。此外，人们还认识到，巴马汀引起的细胞活性下降是由细胞凋亡而不是坏死引起的。此外，用NG-硝基-L-精氨酸甲酯盐酸盐(PAN-NOS抑制剂)抑制诱导型一氧化氮合酶时，巴马汀诱导的破骨细胞不发生凋亡。这些结果表明，巴马汀通过一氧化氮合酶系统在破骨细胞的凋亡中发挥重要作用。因此，巴马汀可作为骨质疏松症骨吸收抑制剂的候选药物。
Osteoporosis is a serious public health problem characterized by low bone density and deterioration of the bone microarchitecture. Current treatment options target either osteoclast resorption or osteoblast formation. It has been reported that berberine, a close structural analog of palmatine, inhibited bone loss in an osteoporosis model. In this study, osseous metabolism was observed in vitro with osteoclast bone resorbing cells. We proved that mouse preosteoclastic cell line (RAW 264.7) has a higher sensitivity to palmatine than mouse osteoblastic cell line (MC3T3-E1); the cell survival rates significantly decreased at 40 μM palmatine. The NO2 − level, a metabolic product of nitric monoxide (NO), and iNOS mRNA expression, an osteoclast with NO induced enzyme, also increased with higher dosage of palmatine. Furthermore, it was recognized that the cell viability decrease from palmatine was caused by apoptosis rather than necrosis. Additionally, osteoclast apoptosis from palmatine did not occur when iNOS was inhibited with NG-nitro-L-arginine methyl ester hydrochloride (pan NOS inhibitor). These results indicate that palmatine plays an important role in osteoclast apoptosis via the NOS system. Hence, palmatine could be considered as a viable pharmaceutical candidate for osteoporosis bone resorption inhibitor.