title: Effect of SDF-1/Cxcr4 Signaling Antagonist AMD3100 on Bone Mineralization in Distraction Osteogenesis.
abstract: Distraction osteogenesis (DO) is a widely applied technique in orthopedics surgery, which involves rapid stem cell migration, homing, and differentiation. Interactions between the chemokine receptor Cxcr4 and its ligand, stromal derived factor-1 (SDF-1), regulate hematopoietic stem cell trafficking to the ischemic area and induce their subsequent differentiation. Here, we examined SDF-1 expression and further investigated the role of SDF-1/Cxcr4 signaling antagonist AMD3100 during bone regeneration in rat DO model. The results showed that expression levels of SDF-1 and osteogenic genes were higher in DO zones than in the fracture zones, and SDF-1 expression level was the highest at the termination of the distraction phase. Radiological, mechanical, and histological analyses demonstrated that the local administration of AMD3100 (400 μM) to DO rats significantly inhibited new bone formation. In the rat bone marrow mesenchymal stem cells culture, comparing to the group treated with osteogenic induction medium, AMD3100 supplement led to a considerable decrease in the expression of alkaline phosphatase and early osteogenic marker genes. However, the amount of calcium deposits in rat MSCs did not differ between the groups. Therefore, our study demonstrated that the DO process induced higher expression of SDF-1, which collated to rapid induction of callus formation. Local application of SDF-1/Cxcr4 signaling antagonist AMD3100 significantly inhibited bone mineralization and osteogenesis in DO, which may represent a potential therapeutic approach to the enhancement of bone consolidation in patients undergoing DO.
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China.
authors.forename: Jia
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Orthopaedics & Traumatology, Stem Cells and Regeneration Laboratory, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Room 904, 9/F, Shatin, Hong Kong Sar, People's Republic of China.|Institute of Orthopedic Diseases and Department of Orthopedics, the First Affiliated Hospital, Jinan University, Guangzhou, People's Republic of China.
authors.forename: Yuanfeng
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Orthopaedics & Traumatology, Stem Cells and Regeneration Laboratory, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Room 904, 9/F, Shatin, Hong Kong Sar, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics & Traumatology, Stem Cells and Regeneration Laboratory, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Room 904, 9/F, Shatin, Hong Kong Sar, People's Republic of China.
authors.forename: Jinfang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China.
authors.forename: Qinglin
authors.initials: Q
authors.lastname: Kang
authors.affiliation: Department of Orthopaedics & Traumatology, Stem Cells and Regeneration Laboratory, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Room 904, 9/F, Shatin, Hong Kong Sar, People's Republic of China.
authors.forename: Kiwai
authors.initials: K
authors.lastname: Ho
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China. ymchai@sjtu.edu.cn.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Chai
authors.affiliation: Department of Orthopaedics & Traumatology, Stem Cells and Regeneration Laboratory, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Room 904, 9/F, Shatin, Hong Kong Sar, People's Republic of China. gangli@cuhk.edu.hk.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
mesh_terms: D000818:Animals; D001596:Benzylamines; D001861:Bone Regeneration; D001842:Bone and Bones / Q000378:metabolism; D002113:Calcification, Physiologic; D002454:Cell Differentiation / Q000502:physiology; D054377:Chemokine CXCL12 / Q000378:metabolism*; D000080027:Cyclams; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology; D010012:Osteogenesis / Q000187:drug effects*; D019857:Osteogenesis, Distraction; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D001596:Benzylamines; C575935:CXCL12 protein, rat; D054377:Chemokine CXCL12; C486264:Cxcr4 protein, rat; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; C088327:plerixafor
keywords: AMD3100; Bone regeneration; Distraction osteogenesis; Fracture; Stromal cell-derived factor-1