Suffruticosol A elevates osteoblast differentiation targeting BMP2-Smad/1/5/8-RUNX2 in pre-osteoblasts.

The Paeonia suffruticosa ANDR. (P. suffruticosa) is commonly used in traditional medicine for various purposes. Suffruticosol A (Suf-A), isolated from P. suffruticosa, is a beneficial compound with antibiofilm, antivirulence, and anti-inflammatory properties. The aim of the present study was to investigate the biological effects of Suf-A on osteogenic processes in pre-osteoblasts. It was determined here in that Suf-A (>98.02%), isolated from P. suffruticosa, showed no cytotoxicity at 0.1-30 μM; however, it induced cytotoxicity at 50-100 μM in pre-osteoblasts. Suf-A increased osteogenic alkaline phosphatase activity and expression levels of noncollagenous proteins. Adhesion and trans-migration on the extracellular matrix were potentiated by Suf-A, but not by wound-healing migration. Suf-A did not affect autophagy or necroptosis during osteoblast differentiation. We found that Suf-A increased runt-related transcription factor 2 (RUNX2) levels and mineralized matrix formation. RUNX2 expression was mediated by Suf-A-induced BMP2-Smad1/5/8 and mitogen-activated protein kinase signaling, as demonstrated by Noggin, a BMP2 inhibitor. These results suggest that Suf-A is a potential natural osteogenic compound.