Rao Leticia G, Krishnadev Nupura, Banasikowska Katharine, Rao A Venket
Division of Endocrinology, St. Michael's Hospital, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
J Med Food. 2003 Summer;6(2):69-78. doi: 10.1089/109662003322233459.
Osteoclasts have been shown to produce reactive oxygen species (ROS) that can stimulate bone resorption. We explored the hypothesis that lycopene, the antioxidant carotenoid from tomatoes, can inhibit mineral resorption by inhibiting osteoclast formation and the production of ROS. Cells from bone marrow prepared from rat femur were plated into 16-well calcium phosphate-coated Osteologic Multi-test Slides and cultured in alpha-minimal essential medium supplemented with dexamethasone, beta-glycerophosphate, and ascorbic acid. The cells were treated with varying doses of lycopene in the absence or presence of parathyroid hormone (PTH) at the start of culture and at each medium change (i.e., every 48 hours). On day 8, mineral resorption pits were quantitated. Similar, parallel experiments were carried out in 12-well plastic dishes to assess tartrate-resistant acid phosphatase (TRAP) activity. Results showed that lycopene inhibited TRAP + formation of multinucleated cells in both vehicle- and PTH-treated cultures. Osteoclasts reduced nitroblue tetrazolium (NBT) to purple-colored formazan, indicating the presence of ROS in these cells. The formazan-staining cells were decreased by treatment with 10(-5) M lycopene, indicating that lycopene inhibited the formation of ROS-secreting osteoclasts. In conclusion, we have shown that lycopene inhibits basal and PTH-stimulated osteoclastic mineral resorption and formation of TRAP + multinucleated osteoclasts, as well as the ROS produced by osteoclasts. These findings are novel and may be important in the pathogenesis, treatment, and prevention of osteoporosis.
破骨细胞已被证明能产生活性氧（ROS），后者可刺激骨吸收。我们探讨了如下假说：番茄中的抗氧化类胡萝卜素番茄红素可通过抑制破骨细胞形成和ROS产生来抑制矿物质吸收。将从大鼠股骨制备的骨髓细胞接种到16孔磷酸钙包被的骨学多测试载玻片上，并在补充了地塞米松、β-甘油磷酸和抗坏血酸的α-最低必需培养基中培养。在培养开始时以及每次更换培养基（即每48小时）时，在不存在或存在甲状旁腺激素（PTH）的情况下，用不同剂量的番茄红素处理细胞。在第8天，对矿物质吸收凹坑进行定量。在12孔塑料培养皿中进行了类似的平行实验，以评估抗酒石酸酸性磷酸酶（TRAP）活性。结果表明，番茄红素在载体处理和PTH处理的培养物中均抑制了多核细胞的TRAP+形成。破骨细胞将硝基蓝四氮唑（NBT）还原为紫色的甲臜，表明这些细胞中存在ROS。用10（-5）M番茄红素处理可减少甲臜染色细胞，表明番茄红素抑制了分泌ROS的破骨细胞的形成。总之，我们已表明番茄红素可抑制基础和PTH刺激的破骨细胞矿物质吸收以及TRAP+多核破骨细胞的形成，以及破骨细胞产生的ROS。这些发现是新颖的，可能在骨质疏松症的发病机制、治疗和预防中具有重要意义。
