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

University of Pittsburgh, United States of America
PLoS ONE (Impact Factor: 3.23). 01/2013; 8(1):e54077. DOI: 10.1371/journal.pone.0054077
Source: PubMed


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.
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.
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.
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.

Download full-text


Available from: Jinglong Yan, May 20, 2015
  • Source
    • "CXCR4 -/-knockout mice exhibit impaired hematopoiesis, defects in heart and brain development and defective vascularization, while the CXCR4 -/-CXCL12 -/-double knockout is embryonic lethal (Ma et al. 1998, Ratajczak et al. 2006). Th is indicates that the CXCR4/CXCL12 axis is important for the organogenesis and tissue repair of non-hematopoietic organs, e.g., kidney, brain and bone (Liu et al. 2013). CXCL12 is produced by bone marrow (BM) stromal cells as major chemoattractant for human CD34 ϩ hematopoietic stem and progenitor cells (HSPC) and is involved in homing, retention and exit from other hematopoietic organs (Aiuti et al. 1997). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: Radioresistance of cancer cells remains a fundamental barrier for maximum efficient radiotherapy. Tumor heterogeneity and the existence of distinct cell subpopulations exhibiting different genotypes and biological behaviors raise difficulties to eradicate all tumorigenic cells. Recent evidence indicates that a distinct population of tumor cells, called cancer stem cells (CSC), is involved in tumor initiation and recurrence and is a putative cause of tumor radioresistance. There is an urgent need to identify the intrinsic molecular mechanisms regulating the generation and maintenance of resistance to radiotherapy, especially within the CSC subset. The chemokine C-X-C motif receptor 4 (CXCR4) has been found to be a prognostic marker in various types of cancer, being involved in chemotaxis, stemness and drug resistance. The interaction of CXCR4 with its ligand, the chemokine C-X-C motif ligand 12 (CXCL12), plays an important role in modulating the tumor microenvironment, angiogenesis and CSC niche. Moreover, the therapeutic inhibition of the CXCR4/CXCL12 signaling pathway is sensitizing the malignant cells to conventional anti-cancer therapy. Content: Within this review we are summarizing the role of the CXCR4/CXCL12 axis in the modulation of CSC properties, the regulation of the tumor microenvironment in response to irradiation, therapy resistance and tumor relapse. Conclusion: In light of recent findings, the inhibition of the CXCR4/CXCL12 signaling pathway is a promising therapeutic option to refine radiotherapy.
    Full-text · Article · Mar 2014 · International Journal of Radiation Biology
  • [Show abstract] [Hide abstract]
    ABSTRACT: An accelerated speed of fracture-healing in patients with traumatic brain injury (TBI) is often encountered in clinical practice. However the mechanisms responsible for this phenomenon are remain unclear. After TBI, many cytokines have been reported change their expressions, suggest that the phenomenon of accelerated speed of fracture-healing may be associated with these cytokines. Semaphorin 3A is a secreted cytokine regulated by neural injury, and it is known to guide axon/dendrite growth and neuronal migration. Recent studies suggest that Semaphorin 3A is so far the only molecule that can regulate bone resorption and formation synchronously. However, a Semaphoring 3A which could perhaps induce enhanced osteogenesis under TBI condition has not yet been identified. Therefore, we presume that Semaphoring 3A may play a key role in accelerated fracture-healing under TBI condition, and these will make Sema3A as a promising potential therapeutic target for facilitating fracture healing.
    No preview · Article · Aug 2013 · Medical Hypotheses
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A form of microscopy that utilizes a photonic crystal biosensor surface as a substrate for cell attachment enables label-free, quantitative, submicron resolution, time-resolved imaging of cell-surface interactions without cytotoxic staining agents or temporally-unstable fluorophores. Other forms of microscopy do not provide this direct measurement of live cell-surface attachment localization and strength that includes unique, dynamic morphological signatures critical to the investigation of important biological phenomena such as stem cell differentiation, chemotaxis, apoptosis, and metastasis. Here, we introduce Photonic Crystal Enhanced Microscopy (PCEM), and apply it to the study of murine dental stem cells to image the evolution of cell attachment and morphology during chemotaxis and drug-induced apoptosis. PCEM provides rich, dynamic information about the evolution of cell-surface attachment profiles over biologically relevant time-scales. Critically, this method retains the ability to monitor cell behavior with spatial resolution sufficient for observing both attachment footprints of filopodial extensions and intracellular attachment strength gradients.
    Full-text · Article · Aug 2013 · The Analyst
Show more