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The aim of this study was to investigate whether arachidonic acid (AA) and docosahexaenoic acid (DHA) affect osteogenesis in osteoblasts and the transdifferentiation into adipocytes. Results from this study show that long\u2010term exposure to AA inhibited alkaline phosphatase (ALP) activity in these cells, which might be prostaglandin E<jats:sub>2<\/jats:sub> (PGE<jats:sub>2<\/jats:sub>)\u2010mediated. DHA exposure also inhibited ALP activity which was evident after both short\u2010 and long\u2010term exposures. The mechanism whereby DHA inhibits ALP activity is not clear and needs to be investigated. Although long\u2010term exposure to PUFAs inhibited ALP activity, the mineralizing properties of these cells were not compromised. Furthermore, PUFA exposure did not induce adipocyte\u2010like features in these cells as evidenced by the lack of cytoplasmic triacylglycerol accummulation. More research is required to elucidate the cellular mechanisms of action of PUFAs on bone. 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