Abstract
Stromal cell-derived factor-1α (SDF-1α) is a key stem cell homing factor that is crucial for recruitment of stem cells to many diseased organs. However, the therapeutic activity of SDF-1α is potentially limited by N-terminal cleavage at position-2 proline by a cell surface protein CD26/dipeptidyl peptidase-IV (DPP-IV). Parathyroid hormone (PTH) is a DPP-IV inhibitor and has been suggested as a promising agent for periodontal tissue repair. The purpose of this study was to explore the effects of a cell-free system comprising SDF-1α and scaffold plus PTH systemic application on periodontal tissue regeneration in vivo. The results showed that PTH/SDF-1α cotherapy improved the quantity of regenerated bone and resulted in better organization of ligament interface. We further investigated the possible mechanisms, and found that PTH/SDF-1α cotherapy enhanced CD90+CD34− stromal cells migration in vivo, increased the number of CXCR4 + cells in periodontal defects, induced early bone osteoclastogenesis and enhanced the expression of runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and collagen I (Col I) in newly formed bone tissue. In conclusion, this cell-free tissue engineering system with local administration of SDF-1α and systemic application of PTH could be employed to induce CD90+CD34− stromal cells recruitment and promote periodontal tissue regeneration.
Highlights
Has been recognized as the most important chemokine for the recruitment and homing of bone marrow-derived mesenchymal stem cells (BMSCs) throughout the mammalian system[14]
In order to investigate the potential of endogenous stromal cell recruitment for periodontal tissue regeneration, an in situ tissue engineering system composed of collagen membrane scaffold loaded with SDF-1αand systemic application of parathyroid hormone (PTH) was developed in this study
The results demonstrated that periodontal tissue regeneration was significantly promoted by collagen membrane loaded with SDF-1αand with systemic injection of PTH
Summary
Has been recognized as the most important chemokine for the recruitment and homing of bone marrow-derived mesenchymal stem cells (BMSCs) throughout the mammalian system[14]. Our previous study demonstrated that local administration of SDF-1αcould recruit stem cells to the periodontal defect, reduce inflammatory responses during the early phase of wound repair, and promote the quantity and quality of newly formed bone[22]. The extent and length of MSCs recruitment depends heavily on the duration and the concentration of SDF-1αrelease, application of exogenous SDF-1αmay be a promising strategy to recruit circulating stem cells and precursor cells to periodontal defect and to promote tissue repair and regeneration. Topical and intermittent administration of PTH recovered alveolar bone loss in rat experimental periodontitis and similar findings were obtained from a randomized clinical-trial in 40 patients with severe periodontitis[30,31] These observations provide credence to the anabolic potential of intermittent application of PTH and its possible relation to reparative process occurring in the periodontium. The purpose of this study was to explore the effects of a cell-free tissue engineering system comprising SDF-1αand scaffold plus PTH systemic application on the recruitment of CD90+CD34− stromal cells and periodontal tissue regeneration in vivo
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