Panax Notoginseng Saponins Stimulate Angiogenesis‐Mediated Bone Formation in Trauma‐Induced Osteonecrosis of the Femoral Head via the PDGF ‐ BB / PDGFR Pathway

Trauma-induced osteonecrosis of the femoral head (TIONFH) is a complex, enigmatic, and rapidly deteriorating orthopedic disease. Many scholars are striving to find noninvasive treatments to stop or reverse TIONFH. Blood vessels in bone tissues, especially the type-H vessels, play an important role in bone remodeling. Panax notoginseng saponins (PNS), also known as the Xuesaitong capsule, are a traditional Chinese medicine widely used in the treatment of ischemia-related diseases. This trial is to explore the effect of PNS on angiogenesis-mediated bone formation in TIONFH. The main components of PNS were identified using UPLC-Q-Orbitrap mass spectrometry. The TIONFH model was surgically established in SD rats, which were subsequently treated with PNS. Four weeks after treatment, the vascularization within the femoral head and the repair of osteonecrosis were evaluated. Rat endothelial progenitor cells (EPCs) were cultured in vitro to examine the effects of PNS on EPCs' proliferation, migration, angiogenesis, and the PDGF-BB/PDGFR pathway. Additionally, EPCs and osteoblasts were co-cultured to analyze the impact of EPC-derived angiogenic-osteogenic factors on osteoblasts' function. Eleven components were identified in PNS through UPLC-Q-Orbitrap mass spectrometry, with saponin being the most predominant among them. In vivo, we observed the presence of type-H vessels within the femoral heads of rats and discovered that PNS could dose-dependently increase the bone mass, type-H vessels' number, PDGF-BB/PDGFR pathway-related factors of rats with the TIONFH. In vitro, PNS-containing serum intervention significantly increased cell viability, migration, angiogenesis, and phosphorylation level of PDGF-BB/PDGFR pathway-related proteins in EPCs. Meanwhile, PNS-containing serum could also reverse the inhibitory effect of PDGFR inhibitor (AG1296) on the EPCs' function. Furthermore, the coculture results of EPCs-osteoblasts confirmed that VEGF derived from EPCs under PNS treatment significantly stimulated the proliferation and mineralization of osteoblasts. In conclusion, PNS could promote angiogenesis-mediated osteogenesis repair in rats with the TIONFH in a dose-dependent manner, which was partly related to the activation and phosphorylation of the PDGF-BB/PDGFR signaling pathway in EPCs.