SDF-1 Promotes Endochondral Bone Repair during Fracture Healing at the Traumatic Brain Injury Condition

Abstract

PurposesThe 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.Materials and MethodsReal-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.ResultsThe 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.ConclusionThe SDF-1/CXCR4 axis plays a crucial role in the accelerating fracture healing under the condition of TBI and contributes to endochondral bone repair.

High glucose microenvironments inhibit the proliferation and migration of bone mesenchymal stem cells by activating GSK3β

“…The expression of CXCR-4 could help MSCs migrate to the sites of bone injury where SDF-1 is upregulated [18][19][20][21], which are necessary for tissue-specific organ repair or regeneration [41][42][43]. So SDF-1 is upregulated at sites of injury and serves as a potent chemoattractant to recruit circulating or resident CXCR4-expressing MSCs.…”

“…Inhibition of GSK3β by LiCl led to increased levels of β-catenin, LEF-1, cyclin D1, and CXCR-4 expression. Our data indicate that GSK3β plays an important role in regulating the ischemic injury SDF-1 modulates cell differentiation into mature reparative cells [15][16][17][18][19][20]. GSK3β is a serine/threonine kinase involved in glucose metabolism and this kinase has, therefore, been proposed to affect cell differentiation, growth, motility, and apoptosis [21,22].…”

“…Recent studies have demonstrated that CXCR-4 could help MSCs migrate to the site of bone injury and for bone repair where the SDF-1 is upregulated [18][19][20][21]. Therefore, we postulated that high glucose microenvironments would affect the SDF-1/CXCR-4 axis during the BMSCs migration process.…”

Stromal cell-derived factor-1 mediates changes of bone marrow stem cells during the bone repair process

“…The intraperitoneal administration of AMD3100 (5 mg/kg) or saline (control) was performed at 1 h before and 8 h after the bone damage procedure (24).…”

Growth factor therapy sequesters inflammation in affording neuroprotection in cerebrovascular diseases

“…SDF-1α acts in a classic chemokine role by attracting T cells and monocytes that are CXCR4+ to the sites of inflammation and aiding in adhesion [70]. It is also critical for the migration of neuroblasts to damaged areas in the brain, and of hematopoetic stem cells to a desired location in the body [72]. …”