3,3′-Diindolylmethane promotes bone formation – A assessment in MC3T3-E1 cells and zebrafish

• Published in: Biochemical pharmacology 2024-12, Vol.230 (Pt 3), p.116618, Article 116618
• Main Authors: Ma, Ying, Zhu, Yin, Wang, Feng, Zhao, Guoyang, Huang, Lianlian, Lu, Rongzhu, Wang, Dongxu, Tian, Xinyu, Ye, Yang
• Format: Article
• Language: English
• Subjects: 3,3′-Diindolylmethane; 3T3 Cells; Animals; BAP1; Cell Differentiation - drug effects; Cell Line; Dose-Response Relationship, Drug; Indoles - pharmacology; IP3R; Mice; Osteoblasts - drug effects; Osteoblasts - metabolism; Osteogenesis - drug effects; Osteoporosis; Osteoporosis - drug therapy; Osteoporosis - metabolism; Store-operated calcium entry; Zebrafish
• ISSN: 0006-2952; 1873-2968; 1873-2968
• DOI: 10.1016/j.bcp.2024.116618

[Display omitted] Osteoporosis is a common degenerative bone disease in middle-aged and elderly people. The current drugs used to treat osteoporosis have many side effects and low patient compliance. Phytochemotherapy may be safer and more effective. 3,3′-diindolemethane (DIM) is the digestive product of indole-3-methanol in cruciferous vegetables in the stomach, which is a kind of anti-tumor and anti-oxidation phytochemical. However, the effects of DIM on osteoblasts and the mechanism by which DIM regulates bone formation are not fully understood. The aim of this study was to investigate the effects of DIM on the bone formation of mouse preosteoblasts MC3T3-E1 and zebrafish. DIM promotes proliferation and osteogenic differentiation of MC3T3-E1 cells in vitro, and also plays a bone promoting role by increasing the interaction between BRCA1-Associated Protein 1(BAP1) and Inositol 1,4,5-Trisphosphate Receptor(IP3R), up-regulating the expression of BAP1 and IP3R and downstream storage operation calcium entry (SOCE) related protein Recombinant Stromal Interaction Molecule 1(STIM1). The effect of DIM on osteoporosis was confirmed in zebrafish osteoporosis model, and its molecular mechanism may be related to BAP1/IP3R/SOCE signaling pathway. These findings highlight the potential therapeutic value of DIM in the prevention and treatment of osteoporosis.