Ishophloroglucin A Isolated From <i>Ishige okamurae</i> Stimulates Osteoblast Differentiation Through Activation of the Bone Morphogenetic Protein and Wnt/β‐Catenin Signaling Pathways in MC3T3‐E1 Cells

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.