Lee Seung-Hong, Kim Mihyang, Jung Kyung Im, Lee Sang-Jae, Park Mi Hwa
Department of Pharmaceutical Engineering, Soonchunhyang University, Asan, Republic of Korea.
Department of Food and Nutrition, College of Medical and Life Science, Silla University, Busan, Republic of Korea.
Cell Biol Int. 2025 Aug;49(8):965-974. doi: 10.1002/cbin.70030. Epub 2025 May 8.
Current osteoporosis treatments are insufficient as they cause a relatively small increase in bone mass and are unable to recover lost bone structures, in addition to having severe side effects. The bone morphogenetic protein (BMP) and Wnt/β-catenin signaling pathways cooperatively modulate bone formation and osteoblast differentiation and therefore may play a role in treating osteoporosis. This study aimed to investigate the effects of Ishophloroglucin A (IPA), a novel phenolic compound isolated from Ishige okamurae, on osteoblast differentiation by activating the BMP and Wnt/β-catenin signaling pathways. According to our findings, IPA significantly promoted the osteogenic proliferation of MC3T3-E1 osteoblastic cells and increased alkaline phosphatase (ALP) activity and calcium nodule formation in MC3T3-E1 cells compared to the untreated control. IPA also upregulated osteogenesis markers such as type 1 collagen, ALP, p-Smad1/5/8, osterix, osteopontin, runt-related transcription factors (Runx2), and BMP2 in MC3T3-E1 cells in a dose-dependent manner. Moreover, IPA activated Wnt3a, LRP5, DVL2, and β-catenin in MC3T3-E1 cells. Overall, our results demonstrate that IPA promotes the differentiation of MC3T3-E1 osteoblastic cells by activating the BMP and Wnt/β-catenin signaling pathways, suggesting that it may be a potential candidate target for treating or preventing osteoporosis.
目前的骨质疏松症治疗方法并不充分,因为它们导致骨量增加相对较少,无法恢复已丢失的骨结构,此外还具有严重的副作用。骨形态发生蛋白(BMP)和Wnt/β-连环蛋白信号通路协同调节骨形成和成骨细胞分化,因此可能在治疗骨质疏松症中发挥作用。本研究旨在探讨从冈村石莼中分离出的一种新型酚类化合物异叶苔素A(IPA)通过激活BMP和Wnt/β-连环蛋白信号通路对成骨细胞分化的影响。根据我们的研究结果,与未处理的对照组相比,IPA显著促进了MC3T3-E1成骨细胞的成骨增殖,并增加了MC3T3-E1细胞中的碱性磷酸酶(ALP)活性和钙结节形成。IPA还以剂量依赖性方式上调了MC3T3-E1细胞中的成骨标志物,如I型胶原、ALP、p-Smad1/5/8、osterix、骨桥蛋白、 runt相关转录因子(Runx2)和BMP2。此外,IPA激活了MC3T3-E1细胞中的Wnt3a、LRP5、DVL2和β-连环蛋白。总体而言,我们的结果表明,IPA通过激活BMP和Wnt/β-连环蛋白信号通路促进MC3T3-E1成骨细胞的分化,表明它可能是治疗或预防骨质疏松症的潜在候选靶点。