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The action of retinol and carotenoids on bone cells was investigation in vitro by evaluating cell growth, alkaline phosphatase activity and the mRNA expression of a differentiation marker protein of osteoblastic cells. The clonal osteogenic cell line MC3T3-E1, established from newborn mouse calvaria, has a capacity of differentiation into osteoblast and mineralization in vitro. Retinol and beta-carotene inhibited the proliferation of MC3T3-E1 cells as well as DNA synthesis of the cells in a dose-dependent manner. Retinol induced differentiation of the MC3T3-E1 cells, by increasing alkaline phosphatase activity dose dependently, in a range from 1 to 100nm. Beta-carotene increased alkaline phosphatase activity is a dose-related manner in a range from 0.1 to 5 microM. Osteopontin is one of the matrix proteins which osteoblasts produce. Retinol increased the expression of osteopontin mRNA in a range from 1 to 100 nm. Beta-carotene also increased osteopontin mRNA expression, reaching a plateau at 1 microM. The induction of differentiation of MC3T3-E11 cells by beta-carotene was dose-dependent but was two orders of magnitude less active than that produced by retinoids. Within the MC3T3-E1 cells, part of the beta-carotene was effectively converted into retinol. Alpha-carotene, canthaxanthin and lycopene also inhibited cell proliferation at 1 microM and increased alkaline phosphatase activity and osteopontin mRNA expression, but less potently so than beta-carotene. Retinol and carotenoids were concluded to have a direct stimulatory effect on the differentiation of osteoblasts at the physiological concentration.

Vitamin A and Carotenoids Stimulate Differentiation of Mouse Osteoblastic Cells.