Low concentration of 3-carene stimulates the differentiation of mouse osteoblastic MC3T3-E1 subclone 4 cells

Recently, natural products have gained more interest as alternative treatments for metabolic bone disorders and for the maintenance of bone health. In this study, the anabolic activities of 89 natural compounds were evaluated by measuring the amount of newly synthesized calcium in the differentiation process of mouse osteoblastic MC3T3-E1 subclone 4 cells. Of these compounds, a low concentration (up to 5 microm) of 3-carene, which is a bicyclic monoterpene in essential oils extracted from pine trees, was shown to stimulate significantly the activity and expression of alkaline phosphatase, an early phase marker of osteoblastic differentiation, on differentiation day 9. On day 15, it dramatically promoted the induction of calcium in a dose-dependent manner. The stimulatory effect of 3-carene on mineralization might be associated with its potential to induce the protein expression/activation of the mitogen-activated protein kinases and the transcript levels of osteoblast mineralization-related genes such as osteopontin and type I collagen. Further studies are needed to determine the precise mechanism, but the anabolic activity of 3-carene in bone metabolism suggested that the use of natural additives to the diet including essential oils could have a beneficial effect on bone health.