Bone mass is regulated by osteoblast-mediated bone formation and osteoclast-mediated bone resorption. Osteoporosis is a bone metabolism disorder in which bone mass decreases due to increased bone resorption rather than bone formation. We focused on the traditional plant Alpinia zerumbet in Okinawa, Japan, and searched for promising compounds for the prevention and treatment of osteoporosis. Pinocembrin isolated from the leaves of A. zerumbet showed enhanced alkaline phosphatase (ALP) activity and mineralization and increased mRNA expression of osteoblast-related genes Alp and Osteocalcin (Ocn) in MC3T3-E1 cells. Pinocembrin increased the mRNA expression of Runx2 and Osterix, which are important transcription factors in osteoblast differentiation, and the mRNA expression of Dlx5 and Msx2, which are enhancers of these transcription factors. The bone morphogenetic protein (BMP) antagonist noggin, its receptor kinase inhibitor LDN-193189 and p38 MAPK inhibitor SB203580 attenuated pinocembrin-promoted ALP activity. Pinocembrin increased the mRNA of Bmp-2 and its target gene Id1. In addition, the estrogen receptor (ER) inhibitor ICI182780 suppressed pinocembrin-stimulated ALP activity. Pinocembrin may increase BMP-2 expression via ER. Then, the BMP-2 promotes osteoblast specific genes expression and mineralization through both Smad-dependent and independent pathway following Runx2 and Osterix induction. Our findings suggest that pinocembrin has bone anabolic effects and may be useful for the prevention and treatment of bone metabolic diseases such as osteoporosis.

骨量受成骨细胞介导的骨形成和破骨细胞介导的骨吸收的调节。骨质疏松症是一种骨代谢紊乱，其中骨量由于骨吸收增加而不是骨形成增加而减少。我们以日本冲绳的传统植物高良姜为研究对象，寻找有前景的化合物用于预防和治疗骨质疏松症。从A.zerumbet叶子中分离的 Pinocembrin 可以增强 MC3T3-E1 细胞中的碱性磷酸酶 (ALP) 活性和矿化作用，并增加成骨细胞相关基因Alp和骨钙素( Ocn ) 的 mRNA 表达。 Pinocembrin 增加了Runx2和Osterix的 mRNA 表达（成骨细胞分化中的重要转录因子）以及Dlx5和Msx2的 mRNA 表达（这些转录因子的增强子）。骨形态发生蛋白 (BMP) 拮抗剂 noggin、其受体激酶抑制剂 LDN-193189 和 p38 MAPK 抑制剂 SB203580 减弱松香素促进的 ALP 活性。 Pinocembrin 增加了Bmp-2及其靶基因Id1的 mRNA。此外，雌激素受体 (ER) 抑制剂 ICI182780 抑制松香素刺激的 ALP 活性。 Pinocembrin 可能通过 ER 增加 BMP-2 的表达。然后，BMP-2 在 Runx2 和 Osterix 诱导后通过 Smad 依赖性和独立途径促进成骨细胞特异性基因表达和矿化。我们的研究结果表明，松柏素具有骨合成代谢作用，可能有助于预防和治疗骨质疏松症等骨代谢疾病。