Limonene attenuates methylglyoxal-induced dysfunction in MC3T3-E1 osteoblastic cells

Abstract

ABSTRACTLimonene is a common natural terpene with powerful antioxidative properties. This study investigated the effects of limonene, a terpene found in citrus fruits, on the function of the murine pre-osteoblast cell line, MC3T3-E1 cells. The results showed that limonene treatment significantly elevated collagen synthesis, alkaline phosphatase activity, osteocalcin synthesis, and mineralization in osteoblastic cells. Methylglyoxal (MG), a highly reactive dicarbonyl metabolite, is a major precursor of advanced glycation end products, which are involved in the pathogenesis of diabetic osteopathy. We therefore investigated the effects of limonene on MG-induced cytotoxicity. Pre-treatment of MC3T3-E1 cells with limonene prevented MG-induced cell death and apoptosis. Limonene also reduced MG-triggered endoplasmic reticulum (ER) stress, as indicated by decreases in the levels of the ER-localized transmembrane signal transducers ATF-6 and IRE1. Furthermore, limonene treatment significantly reduced MG-induced autophagic activity and reactive oxygen species release. These results suggest that limonene may prevent the development of diabetic osteopathy.