Short-chain fatty acids, acetate and propionate, directly upregulate osteoblastic differentiation

Short-chain fatty acids, including acetate, propionate, and butyrate are metabolites of dietary fibre produced by microbiota in the large intestine, have been proposed to contribute to effects on bone homeostasis. However, it is unclear whether they are used in osteoblasts and directly affect bone formation. We investigated whether short-chain fatty acids are absorbed in osteoblast cells and influence early osteoblastic differentiation using MC3T3-E1 cells. Acetate and propionate upregulated alkaline phosphatase activity, which is an osteoblast differentiation marker, and acetate upregulated alkaline phosphatase mRNA expression after treatment for 9 days, whereas butyrate did not in MC3T3-E1 cells. Butyrate was absorbed more rapidly and to a greater extent than acetate and propionate. These results indicate that short-chain fatty acids were used in osteoblastic cells, and particularly acetate and propionate directly upregulated differentiation in primary osteoblasts. Therefore, acetate and propionate might be useful for maintaining a positive balance of bone turnover.