title: Osthole Promotes Endochondral Ossification and Accelerates Fracture Healing in Mice.
abstract: 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.
authors.affiliation: School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
authors.forename: Zhongrong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
authors.forename: Wing Nang
authors.initials: WN
authors.lastname: Leung
authors.affiliation: Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China.
authors.forename: Yau Ming
authors.initials: YM
authors.lastname: Lai
authors.affiliation: School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China. fcwchan@cuhk.edu.hk.
authors.forename: Chun Wai
authors.initials: CW
authors.lastname: Chan
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D003374:Coumarins / Q000494:pharmacology*; D017102:Fracture Healing / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010012:Osteogenesis / Q000187:drug effects*
chemical_list: D000276:Adjuvants, Immunologic; D003374:Coumarins; C046627:osthol
keywords: Bone mineral density; Endochondral ossification; Fracture healing; Molecular imaging; Osthole