Pulsed electromagnetic field (PEMF) has been successfully applied to accelerate fracture repair since 1979. Recent studies suggest that PEMF might be used as a nonoperative treatment for the early stages of osteonecrosis. However, PEMF treatment requires a minimum of ten hours per day for the duration of the treatment. In this study, we modified the protocol of the single-pulsed electromagnetic field (SPEMF) that only requires a 3-minute daily treatment. In the in vitro study, cell proliferation and osteogenic differentiation was evaluated in the hBMSCs. In the in vivo study, new bone formation and revascularization were evaluated in the necrotic bone graft. Results from the in vitro study showed no significant cytotoxic effects on the hBMSCs after 5 days of SPEMF treatment (1 Tesla, 30 pulses per day). hBMSC proliferation was enhanced in the SPEMF-treated groups after 2 and 4 days of treatment. The osteogenic differentiation of hBMSCs was significantly increased in the SPEMF-treated groups after 3–7 days of treatment. Mineralization also increased after 10, 15, 20, and 25 days of treatment in SPEMF-treated groups compared to the control group. The 7-day short-course treatment achieved similar effects on proliferation and osteogenesis as the 25-day treatment. Results from the in vivo study also demonstrated that both the 7-day and 25-day treatments of SPEMF increased callus formation around the necrotic bone and also increased new vessel formation and osteocyte numbers in the grafted necrotic bone at the 2nd and 4th weeks after surgery. In conclusion, the newly developed SPEMF accelerates osteogenic differentiation of cultured hBMSCs and enhances bone repair, neo-vascularization, and cell growth in necrotic bone in mice. The potential clinical advantage of the SPEMF is the short daily application and the shorter treatment course. We suggest that SPEMF may be used to treat fractures and the early stages of osteonecrosis.
Objective: The current study was designed to investigate the effects and underlying mechanisms of adipose tissue-derived stem cells (ADSCs) on hypertrophic scar (HS) fibrosis. Method: Real-time quantitative polymerase chain reaction (qRT-PCR) andWestern blot analysis were performed to detect the expression of collagen I (Col1), collagen III (Col3), and α-smooth muscle actin (α-SMA) after fibroblasts and cultured HS tissues were treated with ADSC medium. All data were analyzed by using SPSS17.0 software. Statistical analysis was performed by Student t tests.Results: The in vitro study showed that ADSC medium decreased the expression of Col1, Col3, and α-SMA. In addition, the protein level of p-p38 was downregulated by ADSC medium treatment in a concentration dependent manner. Conclusion: The current study demonstrated that ADSC could decrease collagen deposition and scar formation in in vitro experiments. The regulation of the p38/ MAPK signaling pathway might play an important role in the process. K E Y W O R D S ADSC, collagen, hypertrophic scars, myofibroblasts, p38/MAPK pathway, α-SMA J Cell Biochem. 2019;120:4057-4064.wileyonlinelibrary.com/journal/jcb
Recent studies have indicated that statins induce osteogenic differentiation both in vitro and in vivo. The molecular mechanism of statin-stimulated osteogenesis is unknown. Activation of RhoA signaling increases cytoskeletal tension, which plays a crucial role in the osteogenic differentiation of mesenchymal stem cells. We thus hypothesized that RhoA signaling is involved in simvastatin-induced osteogenesis in bone marrow mesenchymal stem cells. We found that although treatment with simvastatin shifts localization of RhoA protein from the membrane to the cytosol, the treatment still activates RhoA dose-dependently because it reduces the association with RhoGDIα. Simvastatin also increased the expression of osteogenic proteins, density of actin filament, the number of focal adhesions, and cellular tension. Furthermore, disrupting actin cytoskeleton or decreasing cell rigidity by using chemical agents reduced simvastatin-induced osteogenic differentiation. In vivo study also confirms that density of actin filament is increased in simvastatin-induced ectopic bone formation. Our study is the first to demonstrate that maintaining intact actin cytoskeletons and enhancing cell rigidity are crucial in simvastatin-induced osteogenesis. The results suggested that simvastatin, which is an osteoinductive factor and acts by increasing actin filament organization and cell rigidity combined with osteoconductive biomaterials, may benefit stem-cell-based bone regeneration.
Background: Osteosarcoma is a malignant bone tumor prevalent in adolescents with poor prognosis. Toona sinensis showed potent antiproliferation effect on lung, melatonin, ovary, colon, and liver cancers. However, the effects of the species on osteosarcoma cells are rarely investigated. Results: In this study, we found fraction 1 of Toona sinensis leaf (TSL-1) resulted in inhibition of cell viability in MG-63, Saos-2, and U2OS osteosarcoma cell lines, while it only caused a moderate suppressive effect on normal osteoblasts. In addition, TSL-1 significantly elevated lactate dehydrogenase leakage and induced apoptosis and necrosis in Saos-2 cells. TSL-1 increased mRNA expression of pro-apoptotic factor Bad. Most important, TSL-1 significantly suppressed Saos-2 xenograft tumor growth in nude mice by increasing caspase-3. The IC-50 of TSL-1 for the 3 tested osteosarcoma cells is around 1/9 of that for lung cancer cells. Conclusion: We demonstrated that TSL-1, a fractionated extract from TSL, caused significant cytotoxicity to osteosarcoma cells due to apoptosis. In vivo xenograft study showed that TSL-1 suppressed the growth of osteosarcoma cells at least in part by inducing apoptosis. Our results indicate that TSL-1 has potential to be a promising anti-osteosarcoma adjuvant functional plant extract.
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