ABSTRACT:d
‐pinitol, a naturally occurring inositol derivative found in legumes and soy‐based foods, has shown various biological effects, including anti‐inflammatory and insulin‐sensitizing activities. However, its role in osteoblast differentiation under inflammatory conditions remains unclear. In this study, we investigated whether
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‐pinitol alleviates tumor necrosis factor‐alpha (TNF‐α)‐induced suppression of osteogenic gene expression in MC3T3‐E1 pre‐osteoblasts. Using RT‐PCR, real‐time PCR, and Western blot analyses, we found that
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‐pinitol significantly restored the expression of osteogenic markers inhibited by TNF‐α. Mechanistically,
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‐pinitol treatment markedly suppressed TNF‐α‐mediated upregulation of CREBH and Smurf1, negative regulators of osteoblast differentiation. Importantly,
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‐pinitol strongly induced the expression of β‐galactoside α‐2,6‐sialyltransferase 1 (ST6Gal‐1), and overexpression of ST6Gal‐1 alone also decreased CREBH and Smurf1 expression. Furthermore, both
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‐pinitol and ST6Gal‐1 overexpression attenuated TNF‐α‐induced endoplasmic reticulum (ER) stress markers, including ATF4, ATF6, EDEM, and BiP. These findings collectively suggest that
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‐pinitol promotes osteoblast differentiation under inflammatory stress by inducing ST6Gal‐1 expression, thereby suppressing the CREBH–Smurf1 signaling axis and ER stress pathways. Our results highlight the potential therapeutic implications of
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‐pinitol in managing inflammatory bone diseases.