Radix Salviae miltiorrhizae improves bone microstructure and strength through Wnt/β-catenin and osteoprotegerin/receptor activator for nuclear factor-κB ligand/cathepsin K signaling in ovariectomized rats

Although radix Salviae miltiorrhizae (RSM) is reported to exhibit the antiosteoporotic effect in preclinical study, the underlying mechanism is unclear. To this end, ovariectomized (OVX) rats were employed with administration of RSM (5 g/kg) for 14 weeks. The disturbed serum levels of alkaline phosphatase (ALP), osteoprotegerin (OPG), tartrate-resistant acid phosphatase, and receptor activator of nuclear factor-κB ligand (RANKL) in OVX rats were improved by RSM treatment. Furthermore, supplement of RSM to OVX rats resulted in an increase in femoral bone mineral density and bone strength as well as an improvement in bone microstructures. Moreover, the decreased expression of phosphor (p)-LRP6, insulin-like growth factor-1(IGF-1), ALP, and OPG, as well as increased expression of RANKL and cathepsin K in the tibias and femurs of OVX rats were shifted by RSM treatment. Additionally, RSM reversed the decreased ratio of p-glycogen synthase kinase 3β (GSK3β) to GSK3β and increased ratio of p-β-catenin to β-catenin in OVX rats. Altogether, it is suggestive that RSM improves bone quantity and quality by favoring Wnt/β-catenin and OPG/RANKL/cathepsin K signaling pathways in OVX rats thereby suggesting the potential of this herb to be a novel source of antiosteoporosis drugs.