title: Low-magnitude high-frequency vibration enhanced mesenchymal stem cell recruitment in osteoporotic fracture healing through the SDF-1/CXCR4 pathway.
abstract: Low-magnitude high-frequency vibration (LMHFV) has been proven to promote osteoporotic fracture healing. Mechanical stimulation was reported to enhance SDF-1/CXCR4 signalling in mesenchymal stem cells (MSCs). We hypothesised that LMHFV promoted osteoporotic fracture healing by enhancing MSC migration through the SDF-1/CXCR4 pathway. 152 ovariectomised SD-rats received closed femoral fracture in groups of vibration+MSC (VMG) (20 min/d, 5 d/week), vibration+MSC+AMD3100 (VMAG; AMD, a CXCR4 inhibitor) (1 mg/kg/d, intraperitoneal), MSC (MG) (1 × 106 MSC, intracardiac) or control (CG) for a treatment duration of 2, 4 or 8 weeks. MSC migration was evaluated by ex-vivo green fluorescent protein signal in the callus; and fracture healing was examined by weekly radiographs, endpoint computed-tomography and mechanical test. At week-2 and week-4, ex-vivo callus GFP intensity of VMG was significantly higher than other groups (p < 0.05). From week-2 to week-3, both callus width and callus area in VMG were significantly larger; and from week-7 to week-8, smaller than other groups (p < 0.05). At week-8, high-density bone volume fraction, bone volume fraction, bone mineral density and stiffness in VMG were significantly higher than other 3 groups (p < 0.05). This study demonstrated that LMHFV promoted MSC migration and fracture healing in osteoporotic rats. This effect was attenuated by CXCR4 inhibitor, providing strong evidence that SDF-1-mediated MSC migration was one of the important mechanisms through which LMHFV enhanced fracture healing.
authors.affiliation: General Office, Department of Orthopaedics and Traumatology, 5/F Lui Che Woo Clinical Sciences Building, Prince of Wales Hospital, Shatin, Hong Kong.louis@ort.cuhk.edu.hk.
authors.forename: F Y
authors.initials: FY
authors.lastname: Wei
authors.forename: S K
authors.initials: SK
authors.lastname: Chow
authors.forename: K S
authors.initials: KS
authors.lastname: Leung
authors.forename: J
authors.initials: J
authors.lastname: Qin
authors.forename: A
authors.initials: A
authors.lastname: Guo
authors.forename: O L
authors.initials: OL
authors.lastname: Yu
authors.forename: G
authors.initials: G
authors.lastname: Li
authors.forename: W H
authors.initials: WH
authors.lastname: Cheung
mesh_terms: D000818:Animals; D002146:Bony Callus / Q000473:pathology; D054377:Chemokine CXCL12 / Q000378:metabolism*; D017102:Fracture Healing; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D058866:Osteoporotic Fractures / Q000000981:diagnostic imaging / Q000473:pathology* / Q000628:therapy*; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000378:metabolism*; D015398:Signal Transduction; D014732:Vibration; D055114:X-Ray Microtomography
chemical_list: D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; D049452:Green Fluorescent Proteins