Abstract
Bone marrow adiposity has been associated with several metabolic syndromes such as diabetes and osteoporosis. Imbalance in adipogenic and osteoblastogenic differentiation of human bone marrow mesenchymal stromal cells (hBM-MSCs) was suggested to be the cause of elevated bone marrow adiposity. There are several drugs, of both natural and synthetic origin, to treat bone loss. In this study, as a part of a recent trend to discover natural products with more biocompatibility and fewer side effects to treat bone loss, the effect of hyunganol II (HNG), a coumarin isolated from Corydalis heterocarpa, on hBM-MSC adipogenesis was investigated. Cells treated with HNG showed decreased lipid accumulation indicating a diminished adipocyte phenotype. Treatment with HNG also suppressed the mRNA and protein expressions of PPARγ, C/EBPα, and SREBP1c, and three adipogenic marker genes. Further analysis of MAPK signaling pathway exhibited that HNG treatment elevated ERK activation and suppressed the JNK-mediated cFos and cJun phosphorylation, which inhibits PPARγ transcriptional activity. Taken together, HNG treatment was shown to inhibit adipogenesis via suppressed PPARγ expression as a result of altered MAPK signaling. Therefore, it was suggested that HNG might prevent bone marrow adiposity by inhibiting hBM-MSC adipogenesis and can be utilized as a drug or nutraceutical with beneficial effects on bone. Thus, further studies should be conducted to analyze its effect in vivo.