Molecular mediators involved in Ferulago campestris essential oil effects on osteoblast metabolism

This study was performed to investigate the effects of the essential oil obtained from fruits of Ferulago campestris (FC) on primary calvarial mouse osteoblasts (COBs). The composition of the oil was dominated by monoterpene hydrocarbons (78.8-80.3%), with myrcene (33.4-39.7%), α-pinene (22.7-23.0%), and γ-terpinene (8.1-10.9%) as the major components. Owing to their lipophilic properties, these compounds easily cross cell membranes and affect bone cell function by stimulating or inhibiting specific molecular pathways. We demonstrated, for the first time, that FC oil increased osteoblast proliferation by MAP kinase activation; in addition, oils enhanced the protein kinase AKT, which is known to be critical for control of cell survival, also in presence of the MEK-1 inhibitor PD98059, and this effect was accompanied with a down-regulation of pro-apototic molecules such as Bax and caspases. Interestingly, FC oil significantly increased Runx2 (Runx2/Pebp2αA/AML3) and phospho-Smad1/5/8 protein level, the master regulators of osteoblast differentiation, and their nuclear localization. PD98059 pre-treatment further improved Runx2/phospho-Smads up-regulation. Thus, FC oils influence osteoblast metabolism probably using alternative signaling pathways depending also on the maturation stage of the cells. Taken together our data delineate a positive function of FC oil on osteoblast metabolism, suggesting its possible use as a dietetic integrator in the prevention or in the therapy of pathologies due to impaired bone remodeling.