SDF-1 promotes endochondral bone repair during fracture healing at the traumatic brain injury condition.
OBJECTIVE
The objective of this study was to investigate the role of stromal cell-derived factor-1 (SDF-1) and its receptor, CXCR4, on bone healing and whether SDF-1 contributes to accelerating bone repair in traumatic brain injury (TBI)/fracture model.


METHODS
Real-time polymerase chain reaction and immunohistochemical analysis were used to detect the expression of SDF-1 during the repair of femoral bone in TBI/fracture model. The TBI/fracture model was treated with anti-SDF-1 neutralizing antibody or AMD3100, an antagonist for CXCR4, and evaluated by histomorphometry. In vitro and in vivo migration assays were used to evaluate the functional effect of SDF-1 on primary mesenchymal stem cells.


RESULTS
The expression of SDF1 and CXCR4 messenger RNA was increased during the bone healing in TBI/fracture model but was less increased in fracture only model. High expression of SDF-1 protein was observed in the surrounding tissue of the damaged bone. Treated with anti-SDF-1 antibody or AMD3100 could inhibit new bone formation. SDF-1 increased mesenchymal stem cell chemotaxis in vitro in a dose-dependent manner. The in vivo migration study demonstrated that mesenchymal stem cells recruited by SDF-1 participate in endochondral bone repair.


CONCLUSIONS
The SDF-1/CXCR4 axis plays a crucial role in the accelerating fracture healing under the condition of TBI and contributes to endochondral bone repair.
Department of Orthopedic Surgery, The First Affiliated Hospital, Harbin Medical University, Harbin, P.R. China.
Xiaoqi
X
Liu
Changlong
C
Zhou
Yanjing
Y
Li
Ye
Y
Ji
Gongping
G
Xu
Xintao
X
Wang
Jinglong
J
Yan
D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000494:pharmacology; D001596:Benzylamines; D001930:Brain Injuries / Q000235:genetics* / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects; D000080027:Cyclams; D005269:Femur / Q000187:drug effects / Q000293:injuries / Q000378:metabolism; D017102:Fracture Healing / Q000187:drug effects / Q000235:genetics*; D015870:Gene Expression; D006571:Heterocyclic Compounds / Q000494:pharmacology; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D057134:Antibodies, Neutralizing; D001596:Benzylamines; D054377:Chemokine CXCL12; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; D011994:Recombinant Proteins; C088327:plerixafor