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

• DOI: 10.1002/cbin.70030
• Publication Date: 2025-05-08T13:49:48Z
• Authors: Seung‐Hong Lee; Mihyang Kim; Kyung Im Jung; Sang‐Jae Lee; Mi Hwa Park

ABSTRACTCurrent 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.