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BMC Musculoskeletal Disorders
Published in: BMC Musculoskeletal Disorders 1/2014

Open Access 01-12-2014 | Research article

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

Authors: Song-Shu Lin, Steve WN Ueng, Chi-Chien Niu, Li-Jen Yuan, Chuen-Yung Yang, Wen-Jer Chen, Mel S Lee, Jan-Kan Chen

Published in: BMC Musculoskeletal Disorders | Issue 1/2014

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Abstract

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.
Appendix
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Literature
1.
Korhonen K: Hyperbaric oxygen therapy in acute necrotizing infections. With a special reference to the effects on tissue gas tensions. Ann Chir Gynaecol. 2000, 89 (Suppl 214): 7-36.PubMed
2.
Wang XL, Yang YJ, Xie M, Yu XH, Liu CT, Wang X: Proliferation of neural stem cells correlates with Wnt-3 protein in hypoxic-ischemic neonate rats after hyperbaric oxygen therapy. NeuroReport. 2007, 18: 1753-1756. 10.1097/WNR.0b013e3282f0ec09.CrossRefPubMed
3.
Minear S, Leucht P, Jiang J, Liu B, Zeng A, Fuerer C, Nusse R, Helms JA: Wnt proteins promote bone regeneration. Sci Transl Med. 2010, 2: 29ra30-CrossRefPubMed
4.
Ueng SWN, Lee SS, Lin SS, Wang CR, Liu SJ, Yang HF, Tai CL, Shih CH: Bone healing of tibial lengthening is enhanced by hyperbaric oxygen therapy: a study of bone mineral density and torsional strength on rabbits. J Trauma. 1998, 44: 676-681. 10.1097/00005373-199804000-00020.CrossRefPubMed
5.
Nusse R: Wnts and hedgehogs: lipid-modified proteins and similarities in signaling mechanisms at the cell surface. Development. 2003, 130: 5297-10.1242/dev.00821.CrossRefPubMed
6.
Etheridge SL, Spencer GJ, Heath DJ, Genever PG: Expression profiling and functional analysis of Wnt signaling mechanisms in mesenchymal stem cells. Stem Cells. 2004, 22: 849-860. 10.1634/stemcells.22-5-849.CrossRefPubMed
7.
Logan CY, Nusse R: The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol. 2004, 20: 781-810. 10.1146/annurev.cellbio.20.010403.113126.CrossRefPubMed
8.
De Boer J, Wang HJ, Van Blitterswijk C: Effects of Wnt signaling on proliferation and differentiation of human mesenchymal stem cells. Tissue Eng. 2004, 10: 393-10.1089/107632704323061753.CrossRefPubMed
9.
Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G: Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell. 1997, 89: 747-754. 10.1016/S0092-8674(00)80257-3.CrossRefPubMed
10.
Gaur T, Lengner CJ, Hovhannisyan H, Bhat RA, Bodine PV, Komm BS, Javed A, van Wijnen AJ, Stein JL, Stein GS, Lian JB: Canonical WNT signaling promotes osteogenesis by directly stimulating Runx2 gene expression. J Biol Chem. 2005, 280: 33132-33140. 10.1074/jbc.M500608200.CrossRefPubMed
11.
Lorenowicz MJ, Korswagen HC: Sailing with the Wnt: Charting the Wnt processing and secretion route. Exp Cell Res. 2009, 315: 2683-2689. 10.1016/j.yexcr.2009.06.015.CrossRefPubMed
12.
Cruciat CM, Ohkawara B, Acebron SP, Karaulanov E, Reinhard C, Ingelfinger D, Boutros M, Niehrs C: Requirement of prorenin receptor and vacuolar H+-ATPase-mediated acidification for Wnt signaling. Science. 2010, 327: 459-463. 10.1126/science.1179802.CrossRefPubMed
13.
Verges M: Retromer and sorting nexins in development. Front Biosci. 2007, 12: 3825-3851. 10.2741/2355.CrossRefPubMed
14.
Port F, Kuster M, Herr P, Furger E, Banziger C, Hausmann G, Basler K: Wingless secretion promotes and requires retromer dependent cycling of Wntless. Nat Cell Biol. 2008, 10: 178-185. 10.1038/ncb1687.CrossRefPubMed
15.
Franch-Marro X, Wendler F, Guidato S, Griffith J, Baena-Lopez A, Itasaki N, Maurice MM, Vincent JP: Wingless secretion requires endosome-to-Golgi retrieval of Wntless/Evi/Sprinter by the retromer complex. Nat Cell Biol. 2008, 2008 (10): 170-177.CrossRef
16.
Pattappa G, Heywood HK, de Bruijn JD, Lee DA: The metabolism of human mesenchymal stem cells during proliferation and differentiation. J Cell Physiol. 2010, 226: 2562-CrossRef
17.
Fu J, Jiang M, Mirando AJ, Yu HM, Hsu W: Reciprocal regulation of Wnt and Gpr177/mouse Wntless is required for embryonic axis formation. Proc Natl Acad Sci U S A. 2009, 106: 18598-18603. 10.1073/pnas.0904894106.CrossRefPubMedPubMedCentral
18.
Belenkaya TY, Wu Y, Tang X, Zhou B, Cheng L, Sharma YV, Yan D, Selva EM, Lin X: The retromer complex influences Wnt secretion by recycling Wntless from endosomes to the trans-Golgi network. Dev Cell. 2008, 14: 120-131. 10.1016/j.devcel.2007.12.003.CrossRefPubMed
19.
Coombs GS, Yu J, Canning CA, Veltri CA, Covey TM, Cheong JK, Utomo V, Banerjee N, Zhang ZH, Jadulco RC, Concepcion GP, Bugni TS, Harper MK, Mihalek I, Jones CM, Ireland CM, Virshup DM: WLS-dependent secretion of WNT3A requires Ser209 acylation and vacuolar acidification. J Cell Sci. 2010, 123: 3357-3367. 10.1242/jcs.072132.CrossRefPubMedPubMedCentral
20.
Forgac M: Vacuolar ATPases: rotary proton pumps in physiology and pathophysiology. Nat Rev Mol Cell Biol. 2007, 8: 917-929. 10.1038/nrm2272.CrossRefPubMed
21.
Fehrer C, Brunauer R, Laschober G, Unterluggauer H, Reitinger S, Kloss F, Gully C, Gassner R, Lepperdinger G: Reduced oxygen tension attenuates differentiation capacity of human mesenchymal stem cells and prolongs their lifespan. Aging Cell. 2007, 6: 745-757. 10.1111/j.1474-9726.2007.00336.x.CrossRefPubMed
22.
Holzwarth C, Vaegler M, Gieseke F, Pfister SM, Handgretinger R, Kerst G, Muller I: Low physiologic oxygen tensions reduce proliferation and differentiation of human multipotent mesenchymal stromal cells. BMC Cell Biol. 2010, 11: 11-10.1186/1471-2121-11-11.CrossRefPubMedPubMedCentral
23.
Mazumdar J, O'Brien WT, Johnson RS, LaManna JC, Chavez JC, Klein PS, Simon MC: O2 regulates stem cells through Wnt/β-catenin signalling. Nat Cell Biol. 2010, 12: 1007-1013. 10.1038/ncb2102.CrossRefPubMedPubMedCentral
24.
Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng JM, Behringer RR, de Crombrugghe B: The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell. 2002, 108: 17-29. 10.1016/S0092-8674(01)00622-5.CrossRefPubMed
25.
Banziger C, Soldini D, Schutt C, Zipperlen P, Hausmann G, Basler K: Wntless, a conserved membrane protein dedicated to the secretion of Wnt proteins from signaling cells. Cell. 2006, 125: 509-522. 10.1016/j.cell.2006.02.049.CrossRefPubMed
26.
Bartscherer K, Pelte N, Ingelfinger D, Boutros M: Secretion of Wnt ligands requires Evi, a conserved transmembrane protein. Cell. 2006, 125: 523-533. 10.1016/j.cell.2006.04.009.CrossRefPubMed
27.
Goodman RM, Thombre S, Firtina Z, Gray D, Betts D, Roebuck J, Spana EP, Selva EM: Sprinter: a novel transmembrane protein required for Wg secretion and signaling. Development. 2006, 133: 4901-4911. 10.1242/dev.02674.CrossRefPubMed
28.
Coudreuse DY, Roel G, Betist MC, Destree O, Korswagen HC: Wnt gradient formation requires retromer function in Wnt-producing cells. Science. 2006, 312: 921-924. 10.1126/science.1124856.CrossRefPubMed
29.
George A, Leahy H, Zhou J, Morin PJ: The vacuolar-ATPase inhibitor bafilomycin and mutant VPS35 inhibit canonical Wnt signaling. Neurobiol Dis. 2007, 26: 125-133. 10.1016/j.nbd.2006.12.004.CrossRefPubMed
30.
Korhonen K, Kuttila K, Niinikoski J: Subcutaneous tissue oxygen and carbon dioxide tensions during hyperbaric oxygenation: an experimental study in rats. Eur J Surg. 1999, 165: 885-890. 10.1080/11024159950189401.CrossRefPubMed
31.
Niu CC, Lin SS, Yuan LJ, Chen LH, Wang IC, Tsai TT, Lai PL, Chen WJ: Hyperbaric oxygen treatment suppresses MAPK signaling and mitochondrial apoptotic pathway in degenerated human intervertebral disc cells. J Orthop Res. 2013, 31: 204-209. 10.1002/jor.22209.CrossRefPubMed
32.
Ueng SW, Yuan LJ, Lin SS, Niu CC, Chan YS, Wang IC, Yang CY, Chen WJ: Hyperbaric oxygen treatment prevents nitric oxide-induced apoptosis in articular cartilage injury via enhancement of the expression of heat shock protein 70. J Orthop Res. 2013, 31: 376-384. 10.1002/jor.22235.CrossRefPubMed
Metadata
Title
Effects of hyperbaric oxygen on the osteogenic differentiation of mesenchymal stem cells
Authors
Song-Shu Lin
Steve WN Ueng
Chi-Chien Niu
Li-Jen Yuan
Chuen-Yung Yang
Wen-Jer Chen
Mel S Lee
Jan-Kan Chen
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2014
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/1471-2474-15-56

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