Jung Dong Ho, Kim Hye Jin, Ryuk Jin Ah, Ko Byoung-Seob, Kim Yong-Bum, Myung Chang-Seon, Im Wan-Jung
KM Convergence Research Division, Korea Institute of Oriental Medicine, 1672 Yuseongdae-ro, Yuseong-gu, Daejeon 34054, Republic of Korea; Department of Pharmacology, College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea.
KM Convergence Research Division, Korea Institute of Oriental Medicine, 1672 Yuseongdae-ro, Yuseong-gu, Daejeon 34054, Republic of Korea.
Biomed Pharmacother. 2025 Aug;189:118294. doi: 10.1016/j.biopha.2025.118294. Epub 2025 Jun 25.
Proper bone development during the growth phase is essential for achieving normal skeletal length, mineral density, and strength, which is regulated by growth hormones, vitamin D, and calcium. Deficiencies in these elements can impair skeletal formation, increasing the risk of disorders such as rickets and osteoporosis. Therefore, natural compounds with bone-supportive effects are of growing interest. Sedum sarmentosum (S. sarmentosum), a plant traditionally used in Korea to treat liver disorders, contains abundant vitamin C and calcium, however, its effects on bone development remain unclear. We found that oral administration of an aqueous extract of S. sarmentosum (SS-Ex) improved trabecular bone structure and bone mineral density in mice fed a calcium- and vitamin D-deficient diet. SS-Ex treated mice showed increased growth plate thickness and elevated serum levels of osteocalcin (Ocn), type I collagen alpha 1 (Col1a1), calcium, and calcitonin. In vitro, SS-Ex enhanced alkaline phosphatase (Alp) activity and promoted mineral deposition in MC3T3-E1 pre-osteoblasts. Additionally, SS-Ex upregulated osteogenic genes including runt-related transcription factor 2, osterix, Ocn, osteopontin, Alp, and Col1a1. Whereas mechanistically, SS-Ex downregulated the expression of dickkopf-related protein 1, a negative regulator of the wingless-type MMTV integration site (Wnt)/β-Catenin pathway, thereby activating Wnt3a/β-Catenin signaling. Moreover, SS-Ex upregulated the expression of bone morphogenetic protein 2 (Bmp2), further enhancing osteogenic signaling. These findings suggest that SS-Ex promotes osteoblast differentiation, supports linear bone growth via growth plate stimulation, and helps maintain calcium balance, indicating its potential as a natural agent for enhancing bone development during growth.
生长阶段的骨骼正常发育对于实现正常的骨骼长度、矿物质密度和强度至关重要，这一过程受生长激素、维生素D和钙的调节。这些元素的缺乏会损害骨骼形成，增加佝偻病和骨质疏松症等疾病的风险。因此，具有骨骼支持作用的天然化合物越来越受到关注。垂盆草是一种在韩国传统上用于治疗肝脏疾病的植物，含有丰富的维生素C和钙，然而，其对骨骼发育的影响尚不清楚。我们发现，口服垂盆草水提取物（SS-Ex）可改善饲喂钙和维生素D缺乏饮食小鼠的小梁骨结构和骨矿物质密度。接受SS-Ex治疗的小鼠生长板厚度增加，血清骨钙素（Ocn）、I型胶原蛋白α1（Col1a1）、钙和降钙素水平升高。在体外，SS-Ex增强了碱性磷酸酶（Alp）活性，并促进了MC3T3-E1前成骨细胞中的矿物质沉积。此外，SS-Ex上调了包括 runt相关转录因子2、osterix、Ocn、骨桥蛋白、Alp和Col1a1在内的成骨基因。从机制上来说，SS-Ex下调了无翅型MMTV整合位点（Wnt）/β-连环蛋白信号通路的负调节因子Dickkopf相关蛋白1的表达，从而激活Wnt3a/β-连环蛋白信号。此外，SS-Ex上调了骨形态发生蛋白2（Bmp2）的表达，进一步增强了成骨信号。这些发现表明，SS-Ex促进成骨细胞分化，通过刺激生长板支持线性骨骼生长，并有助于维持钙平衡，表明其作为促进生长期间骨骼发育的天然药物的潜力。
