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Osthole has been found to restore bone mass in preclinical osteoporotic models. In the present study, we investigated the effects of osthole on bone fracture repair in mice. Adult C57BL/6 mice were subjected to transverse femoral fractures and administrated orally with 20 mg/kg osthole and vehicle solvent daily from week 1 post-operation. Fracture callus were analyzed by plain radiography, micro-computed tomography, histology, molecular imaging and immunohistochemistry and tartrate-resistant acid phosphatase staining. Results demonstrated that osthole treatment enhanced removal of cartilage and bony union during reparative stage without significant interfering on remodeling process. In vivo molecular imaging showed bone formation rate of the treatment group was almost twofold of control group at week 2 post-operation. Osthole augmented the expression of alkaline phosphatase and collagen type X in hypertrophic chondrocytes as well as expression of bone morphogenetic protein-2, osteocalcin and alkaline phosphatase in osteoblastic cells, indicating it promoted mineralization of hypertrophic cartilage and woven bone growth simultaneously during endochondral healing. In summary, osthole promotes endochondral ossification via upregulation of maturation osteogenic marker genes in chondrocytes and subsequently accelerates fracture repair and bony fusion. [ABSTRACT FROM AUTHOR]

Abstract: Computed radiography (CR) and a combined ultrasound (US) approach involving two-dimensional (2-D) and three-dimensional (3-D) ultrasonography with ultrasonometry were employed to evaluate their respective efficacies in monitoring bone regeneration during rabbit tibial distraction osteogenesis (DO). Results demonstrated that 2-D and 3-D ultrasonography depicted bone callus growth changes during distraction while CR could not. Evaluation of callus speed of sound, acoustic reflection and attenuation showed significant linear changes over time during early DO stage (p < 0.05). However, surrogate measure of callus density by CR only showed such significant linear changes during consolidation (p < 0.05). Also, callus speed of sound and acoustic reflection during early DO stage showed strong predictions to the bone mineral density and microstructural properties (adjusted-R2 = 0.43–0.67) of consolidated bone callus measured at the treatment end-point by microcomputed tomography. Findings of the present study indicated a preferred use of the combined US approach over CR in the early monitoring of bone regeneration during DO treatment. [Copyright &y& Elsevier]