Department of Biotechnology, School of Engineering, Daegu University, Gyeongsan 38453, Republic of Korea.
Research Institute of Anti-Aging, Daegu University, Gyeongsan 38453, Republic of Korea.
Cells. 2023 Jul 15;12(14):1863. doi: 10.3390/cells12141863.
Policosanol is known as a hypocholesterolemic compound and is derived from plants such as sugar cane and corn. Policosanol can lower blood pressure or inhibit adipogenesis, but its effect on osteogenic differentiation and the molecular mechanism is unclear. This study aims to investigate the effect of policosanol on osteogenic differentiation in MC3T3-E1 cells and zebrafish models. Administration of policosanol into MC3T3-E1 induced the expression of the osteogenic genes such as distal-less homeobox 5 (Dlx5) and runt-related transcription factor 2 (Runx2). Alkaline phosphatase activity and extracellular mineralization also increased. Policosanol promoted activation of adenosine monophosphate-activated protein kinase (AMPK) and insulin-induced genes (INSIGs) expression and regulation of INSIGs modulated osteoblast differentiation. AMPK activation through transfection of the constitutively active form of AMPK (CA-AMPK) increased INSIGs expression, whereas policosanol-induced INSIGs expression was suppressed by inhibitor of AMPK (Com. C). Furthermore, the osteogenic effects of policosanol were verified in zebrafish. Amputated caudal fin rays were regenerated by policosanol treatment. Taken together, these results show that policosanol increases osteogenic differentiation and contributes to fin regeneration in zebrafish via AMPK-mediated INSIGs expression, suggesting that policosanol has potential as an osteogenic agent.
植物醇是一种降胆固醇化合物，来源于甘蔗和玉米等植物。植物醇可以降低血压或抑制脂肪生成，但它对成骨分化的影响及其分子机制尚不清楚。本研究旨在探讨植物醇对 MC3T3-E1 细胞和成鱼模型成骨分化的影响。植物醇处理 MC3T3-E1 可诱导成骨基因如远侧同源盒 5（Dlx5）和 runt 相关转录因子 2（Runx2）的表达。碱性磷酸酶活性和细胞外矿化也增加。植物醇促进了腺苷单磷酸激活蛋白激酶（AMPK）和胰岛素诱导基因（INSIGs）的表达，调节 INSIGs 可调节成骨细胞分化。通过转染 AMPK 的组成型激活形式（CA-AMPK）激活 AMPK 增加了 INSIGs 的表达，而抑制剂 AMPK（Com.C）抑制了植物醇诱导的 INSIGs 表达。此外，还在斑马鱼中验证了植物醇的成骨作用。植物醇处理可再生截尾的尾鳍。综上所述，这些结果表明，植物醇通过 AMPK 介导的 INSIGs 表达增加成骨分化，并有助于斑马鱼的鳍再生，表明植物醇具有作为成骨剂的潜力。
