Platelet-rich plasma promotes bone formation, restrains adipogenesis and accelerates vascularization to relieve steroids-induced osteonecrosis of the femoral head.

Steroid-associated necrosis of the femoral head (SANFH) is one of the most common and refractory chronic diseases with increasing incidence. The typical pathological changes of SANFH include decreased osteogenic differentiation, enhanced intramedullary adipocytes deposition and impaired osseous circulation. In this study, we investigated the effects and potential mechanisms of Platelet-rich plasma (PRP) on SANFH. Sixty Sprague-Dawley rats were randomly divided into the control, PRP donor, model, and PRP groups. Compared to the model group, PRP treatment significantly increased the hemorheological indexes and serum levels of bone gla-protein (BGP) and vascular endothelial growth factor (VEGF), while decreased the levels of triglyceride (TG) and total cholesterol (TC). Meanwhile, Micro-CT and histopathological stain (Hematoxylin-eosin and Alcian blue-hematoxylin/orange G staining) were performed on the femoral head for morphological and histopathological evaluation, indicating that bone trabecular microstructure and bone mineral density (BMD) were significantly improved after PRP treatment. Immunohistochemical analysis revealed that PRP remarkably up-regulated the expression of osteogenic markers including ß-catenin and alkaline phosphatase (ALP), angiogenic markers containing VEGF and platelet endothelial cell adhesion molecule-1 (CD31), while down-regulated adipogenic markers involving fatty acid-binding protein (FABP-4), and peroxisome proliferator-activated receptor gamma (PPAR-γ) in SANFH rat models. In summary, for the first time, PRP was demonstrated to prevent the development of SANFH through stimulating bone formation and vascularization as well as retarding adipogenesis.

Predication of the underlying mechanism of Bushenhuoxue formula acting on knee osteoarthritis via network pharmacology-based analyses combined with experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Knee osteoarthritis (KOA) is the most common chronic joint disorder worldwide, which is also a principle consideration for disability. The Bushenhuoxue formula (BSHXF) is a traditional herbal formula which widely applied to the treatment of KOA. However, its pharmacological mechanisms of action have not been clarified. AIMS OF THE STUDY: The study aimed to identify the potential targets and mechanisms of BSHXF in the treatment of KOA through pharmacology-based analyses and experimental validation. MATERIALS AND METHODS: The TCMSP database was applied to obtain the chemical compounds and targets of BSHXF, while the protein targets in KOA were determined through GeneCards and OMIM databases. The herb-compound-target and protein-protein interaction (PPI) networks were constructed for topological analyses and hub-targets screening. GO and KEGG enrichment analyses were performed on these core nodes to identify the critical biological processes and signaling pathways. Then destabilization of medial meniscus (DMM)-induced C57BL/6J mice model was established to detect the level of apoptosis via TUNEL assessment, while the expressions of CASP3, CASP8 and CASP9 were determined by immunohistochemistry. RESULTS: A total of 154 active compounds and 58 targets were predicted. DAVID, ClueGO and Metascape enrichment analyses all proved that BSHXF plays an essential role in regulating apoptosis. Moreover, 3 central nodes of BSHXF are recognized as the active factors involved in the main biological functions, suggesting a potential mechanism of BSHXF for KOA treatment. In vivo experiment revealed that BSHXF significantly inhibited apoptosis and down-regulated the expressions of CASP3, CASP8 and CASP9. CONCLUSION: Based on network pharmacology and experimental validation, our study indicated that BSHXF exerted anti-apoptosis effect through inhibiting the expressions of CASP3, CASP8 and CASP9, which could be considered as an effective method for KOA treatment.