Structural characterization and osteogenic potential of polysaccharide purified from Sanghuangporus vaninii

Sanghuangporus vaninii (S. vaninii) is a fungus of considerable medicinal properties. Nevertheless, the specific effects of polysaccharides derived from S. vaninii on bone tissues and their underlying mechanisms remain underexplored. In this research, we purified polysaccharide (SVP-a2) from S. vaninii and systematically explored its structural composition and the anti-osteoporotic characteristics via promoting bone formation. SVP-a2 is a novel neutral polysaccharide exhibiting a molecular weight of 23.593 kDa, predominantly constituted by →6)-α-Galp-(1→. The substitutions are observed at specific C-2 positions, involving the α-Manp-(1 → or α-Manp-(1 → 2)-α-Fucp-(1→. In the dexamethasone-induced osteoporosis (OP) mice model, SVP-a2 significantly restored the bone microstructure, enhanced bone density and trabecular connectivity, and markedly promoted the osteogenic differentiation in the bone tissue. Through the combined analysis of serum metabolomics, bone tissue proteomics and biological assays, SVP-a2 was found to modulate bone metabolism by regulating mineral absorption. SVP-a2 activated the fibroblast growth factor 2/Wnt signaling pathway, inhibited glycogen synthase kinase-3β phosphorylation, promoted osteogenic differentiation, enhanced bone formation, and thereby exerted an anti-OP effect. This research furnishes a therapeutic approach for using SVP-a2 as a functional constituent in the clinical adjunctive therapy of OP, and presents an innovative theoretical foundation for the development of polysaccharide-based bone metabolism regulator.