Effects of hyperbaric oxygen on the osteogenic differentiation of mesenchymal stem cells

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• 作者：Song-Shu Lin (10) (8)
  Steve WN Ueng (10)
  Chi-Chien Niu (10)
  Li-Jen Yuan (10)
  Chuen-Yung Yang (10)
  Wen-Jer Chen (10)
  Mel S Lee (10)
  Jan-Kan Chen (9)
  
• 关键词：Hyperbaric oxygen ; Mesenchymal stem cells ; Wntless ; Retromer trafficking protein ; Vacuolar ATPases
• 刊名：BMC Musculoskeletal Disorders
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：15
• 期：1
• 全文大小：994 KB
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  33. The pre-publication history for this paper can be accessed here: http://www.biomedcentral.com/1471-2474/15/56/prepub
  
• 作者单位：Song-Shu Lin (10) (8)
  Steve WN Ueng (10)
  Chi-Chien Niu (10)
  Li-Jen Yuan (10)
  Chuen-Yung Yang (10)
  Wen-Jer Chen (10)
  Mel S Lee (10)
  Jan-Kan Chen (9)
  
  10. Department of Orthopaedic, Chang Gung Memorial Hospital, No 5, Fu-Hsing Street, 333, Taoyuan, Taiwan
  8. Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan
  9. Department of Physiology, College of medicine, Chang Gung University, 259 Wen-Hwa 1st Road, 333, Kweishan, Taoyuan, Taiwan
  
• ISSN：1471-2474

文摘

Background Hyperbaric oxygenation was shown to increase bone healing in a rabbit model. However, little is known about the regulatory factors and molecular mechanism involved.We hypothesized that the effect of hyperbaric oxygen (HBO) on bone formation is mediated via increases in the osteogenic differentiation of mesenchymal stem cells (MSCs) which are regulated by Wnt signaling. Methods The phenotypic characterization of the MSCs was analyzed by flow cytometric analysis. To investigate the effects of HBO on Wnt signaling and osteogenic differentiation of MSCs, mRNA and protein levels of Wnt3a, beta-catenin, GSK-3beta, Runx 2, as well as alkaline phosphatase activity, calcium deposition, and the intensity of von Kossa staining were analyzed after HBO treatment. To investigate the effects of HBO on Wnt processing and secretion, the expression of Wntless and vacuolar ATPases were quantified after HBO treatment. Results Cells expressed MSC markers such as CD105, CD146, and STRO-1. The mRNA and protein levels of Wnt3a, β-catenin, and Runx 2 were up-regulated, while GSK-3β was down-regulated after HBO treatment. Western blot analysis showed an increased β-catenin translocation with a subsequent stimulation of the expression of target genes after HBO treatment. The above observation was confirmed by small interfering (si)RNA treatment. HBO significantly increased alkaline phosphatase activity, calcium deposition, and the intensity of von Kossa staining of osteogenically differentiated MSCs. We further showed that HBO treatment increased the expression of Wntless, a retromer trafficking protein, and vacuolar ATPases to stimulate Wnt processing and secretion, and the effect was confirmed by siRNA treatment. Conclusions HBO treatment increased osteogenic differentiation of MSCs via regulating Wnt processing, secretion, and signaling.