Low-intensity pulsed ultrasound accelerates fracture healing by stimulation of recruitment of both local and circulating osteogenic progenitors.
ABSTRACT We investigated the effect of low-intensity pulsed ultrasound (LIPUS) on the homing of circulating osteogenic progenitors to the fracture site. Parabiotic animals were formed by surgically conjoining a green fluorescent protein (GFP) mouse and a syngeneic wild-type mouse. A transverse femoral fracture was made in the contralateral hind limb of the wild-type partner. The fracture site was exposed to daily LIPUS in the treatment group. Animals without LIPUS treatment served as the control group. Radiological assessment showed that the hard callus area was significantly greater in the LIPUS group than in the control group at 2 and 4 weeks post-fracture. Histomorphometric analysis at the fracture site showed a significant increase of GFP cells in the LIPUS group after 2 weeks (7.5%), compared to the control group (2.4%) (p < 0.05). The LIPUS group exhibited a significantly higher percentage of GFP cells expressing alkaline phosphatase (GFP/AP) than the control group at 2 weeks post-fracture (5.9%, 0.3%, respectively, p < 0.05). There was no significant difference in the percentage of GFP/AP cells between the LIPUS group (2.0%) and the control group (1.4%) at 4 weeks post-fracture. Stromal cell derived factor-1 and CXCR4 were immunohistochemically identified at the fracture site in the LIPUS group. These data indicate that LIPUS induced the homing of circulating osteogenic progenitors to the fracture site for possible contribution to new bone formation.
- [show abstract] [hide abstract]
ABSTRACT: Sphingosine-1-phosphate (S1P) has recently been recognized as a crucial coupling molecule of osteoclast and osteoblast activity provoking osteoanabolic effects. Targeting S1P receptors could, therefore, be a potential strategy to support bone formation in osteopenic diseases or in fracture repair. Here we investigated whether systemic treatment with the S1P analog FTY720 (Fingolimod) could improve fracture healing. Twelve-week-old, female C57BL/6 mice received an osteotomy of the femur, which was stabilized using an external fixator. The mice received a daily subcutaneous injection of either FTY720 (6 mg/kg) or vehicle from the third postoperative day. Fracture healing was evaluated after 10 and 21 days using biomechanical testing, µ-computed tomography, and histomorphometry. Because FTY720 is supposed to influence osteoclast recruitment, osteoclasts were identified in the fracture callus by staining for tartrate resistant acid phosphatase (TRAP). There were no significant differences in callus mechanical properties, tissue composition and osteoclast number between the groups, suggesting that systemically applied FTY720 did not influence bone regeneration in this model of regular fracture healing. Even if further studies should test the potency of FTY720 under unfavorable healing conditions, we conclude that the effect of systemically applied FTY720 on fracture healing might be inferior compared to other anabolic treatments. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.Journal of Orthopaedic Research 07/2013; · 2.88 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Low-intensity pulsed ultrasound (LIPUS) acting on induced pluripotent stem cells-derived neural crest stem cells (iPSCs-NCSCs) is considered a promising therapy to improve the efficacy of injured peripheral nerve regeneration. Effects of LIPUS on cell viability, proliferation and neural differentiation of iPSCs-NCSCs were examined respectively in this study. LIPUS at 500 mW cm(-2) enhanced the viability and proliferation of iPSCs-NCSCs after 2 days and, after 4 days, up-regulated gene and protein expressions of NF-M, Tuj1, S100β and GFAP in iPSCs-NCSCs whereas after 7 days expression of only NF-M, S100β and GFAP were up-regulated. LIPUS treatment at an appropriate intensity can, therefore, be an efficient and cost-effective method to enhance cell viability, proliferation and neural differentiation of iPSCs-NCSCs in vitro for peripheral nerve tissue engineering.Biotechnology Letters 09/2013; · 1.85 Impact Factor