Advertisement

Different effects of intermittent and continuous fluid shear stresses on osteogenic differentiation of human mesenchymal stem cells

  • Liyue Liu
  • Bin Yu
  • Jiarong Chen
  • Zihua Tang
  • Chen Zong
  • Dan Shen
  • Qiang Zheng
  • Xiangming Tong
  • Changyou Gao
  • Jinfu Wang
Original Paper

Abstract

A reasonable mechanical microenvironment similar to the bone microenvironment in vivo is critical to the formation of engineering bone tissues. As fluid shear stress (FSS) produced by perfusion culture system can lead to the osteogenic differentiation of human mesenchymal stem cells (hMSCs), it is widely used in studies of bone tissue engineering. However, effects of FSS on the differentiation of hMSCs largely depend on the FSS application manner. It is interesting how different FSS application manners influence the differentiation of hMSCs. In this study, we examined the effects of intermittent FSS and continuous FSS on the osteogenic differentiation of hMSCs. The phosphorylation level of ERK1/2 and FAK is measured to investigate the effects of different FSS application manners on the activation of signaling molecules. The results showed that intermittent FSS could promote the osteogenic differentiation of hMSCs. The expression level of osteogenic genes and the alkaline phosphatase (ALP) activity in cells under intermittent FSS application were significantly higher than those in cells under continuous FSS application. Moreover, intermittent FSS up-regulated the activity of ERK1/2 and FAK. Our study demonstrated that intermittent FSS is more effective to induce the osteogenic differentiation of hMSCs than continuous FSS.

Keywords

hMSCs Osteogenesis FSS Perfusion culture 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Arnsdorf EJ, Tummala P, Kwon RY, Jacobs CR (2009) Mechanically induced osteogenic differentiation—the role of RhoA, ROCKII and cytoskeletal dynamics. J Cell Sci 122: 546–553CrossRefGoogle Scholar
  2. Bancroft GN, Sikavitsas VI, van den Dolder J, Sheffield TL, Ambrose CG, Jansen JA, Mikos AG (2002) Fluid flow increases mineralized matrix deposition in 3D perfusion culture of marrow stromal osteoblasts in a dose-dependent manner. Proc Natl Acad Sci USA 99: 12600–12605CrossRefGoogle Scholar
  3. Boudreau NJ, Jones PL (1999) Extracellular matrix and integrin signalling: the shape of things to come. Biochem J 339(Pt 3): 481–488CrossRefGoogle Scholar
  4. Brand RA, Stanford CM (1994) How connective tissues temporally process mechanical stimuli. Med Hypotheses 42: 99–104CrossRefGoogle Scholar
  5. Cheung PF, Wong CK, Ip WK, Lam CW (2008) FAK-mediated activation of ERK for eosinophil migration: a novel mechanism for infection-induced allergic inflammation. Int Immunol 20: 353–363CrossRefGoogle Scholar
  6. Digirolamo CM, Stokes D, Colter D, Phinney DG, Class R, Prockop DJ (1999) Propagation and senescence of human marrow stromal cells in culture: a simple colony-forming assay identifies samples with the greatest potential to propagate and differentiate. Br J Haematol 107: 275–281CrossRefGoogle Scholar
  7. Dumas V, Ducharne B, Perrier A, Fournier C, Guignandon A, Thomas M, Peyroche S, Guyomar D, Vico L, Rattner A (2010) Extracellular matrix produced by osteoblasts cultured under low-magnitude, high-frequency stimulation is favourable to osteogenic differentiation of mesenchymal stem cells. Calcif Tissue Int 87: 351–364CrossRefGoogle Scholar
  8. Glossop JR, Cartmell SH (2009) Effect of fluid flow-induced shear stress on human mesenchymal stem cells: differential gene expression of IL1B and MAP3K8 in MAPK signaling. Gene Expr Patterns 9: 381–388CrossRefGoogle Scholar
  9. Grellier M, Bareille R, Bourget C, Amedee J (2009) Responsiveness of human bone marrow stromal cells to shear stress. J Tissue Eng Regen Med 3: 302–309CrossRefGoogle Scholar
  10. Guignandon A, Usson Y, Laroche N, Lafage-Proust MH, Sabido O, Alexandre C, Vico L (1997) Effects of intermittent or continuous gravitational stresses on cell-matrix adhesion: quantitative analysis of focal contacts in osteoblastic ROS 17/2.8 cells. Exp Cell Res 236: 66–75CrossRefGoogle Scholar
  11. Gurkan UA, Akkus O (2008) The mechanical environment of bone marrow: a review. Ann Biomed Eng 36: 1978–1991CrossRefGoogle Scholar
  12. Haasper C, Jagodzinski M, Drescher M, Meller R, Wehmeier M, Krettek C, Hesse E (2008) Cyclic strain induces FosB and initiates osteogenic differentiation of mesenchymal cells. Exp Toxicol Pathol 59: 355–363CrossRefGoogle Scholar
  13. Haudenschild AK, Hsieh AH, Kapila S, Lotz JC (2009) . Ann Biomed Eng 37: 492–502CrossRefGoogle Scholar
  14. Hosseinkhani H, Inatsugu Y, Hiraoka Y, Inoue S, Tabata Y (2005) Perfusion culture enhances osteogenic differentiation of rat mesenchymal stem cells in collagen sponge reinforced with poly(glycolic Acid) fiber. Tissue Eng 11: 1476–1488CrossRefGoogle Scholar
  15. Huang CH, Chen MH, Young TH, Jeng JH, Chen YJ (2009) Interactive effects of mechanical stretching and extracellular matrix proteins on initiating osteogenic differentiation of human mesenchymal stem cells. J Cell Biochem 108: 1263–1273CrossRefGoogle Scholar
  16. Inoue D, Kido S, Matsumoto T (2004) Transcriptional induction of FosB/DeltaFosB gene by mechanical stress in osteoblasts. J Biol Chem 279: 49795–49803CrossRefGoogle Scholar
  17. Irigoyen JP, Nagamine Y (1999) Cytoskeletal reorganization leads to induction of the urokinase-type plasminogen activator gene by activating FAK and Src and subsequently the Ras/Erk signaling pathway. Biochem Biophys Res Commun 262: 666–670CrossRefGoogle Scholar
  18. Kanno T, Takahashi T, Tsujisawa T, Ariyoshi W, Nishihara T (2007) Mechanical stress-mediated Runx2 activation is dependent on Ras/ERK1/2 MAPK signaling in osteoblasts. J Cell Biochem 101: 1266–1277CrossRefGoogle Scholar
  19. Kapur S, Baylink DJ, Lau KH (2003) Fluid flow shear stress stimulates human osteoblast proliferation and differentiation through multiple interacting and competing signal transduction pathways. Bone 32: 241–251CrossRefGoogle Scholar
  20. Kim SH, Choi YR, Park MS, Shin JW, Park KD, Kim SJ, Lee JW (2007) ERK 1/2 activation in enhanced osteogenesis of human mesenchymal stem cells in poly(lactic-glycolic acid) by cyclic hydrostatic pressure. J Biomed Mater Res A 80: 826–836Google Scholar
  21. Kreke MR, Sharp LA, Lee YW, Goldstein AS (2008) Effect of intermittent shear stress on mechanotransductive signaling and osteoblastic differentiation of bone marrow stromal cells. Tissue Eng Part A 14: 529–537CrossRefGoogle Scholar
  22. LaMothe JM, Zernicke RF (2004) Rest insertion combined with high-frequency loading enhances osteogenesis. J Appl Physiol 96: 1788–1793CrossRefGoogle Scholar
  23. Lee DY, Yeh CR, Chang SF, Lee PL, Chien S, Cheng CK, Chiu JJ (2008) Integrin-mediated expression of bone formation-related genes in osteoblast-like cells in response to fluid shear stress: roles of extracellular matrix, Shc, and mitogen-activated protein kinase. J Bone Miner Res 23: 1140–1149CrossRefGoogle Scholar
  24. Liu L, Yuan W, Wang J (2010) Mechanisms for osteogenic differentiation of human mesenchymal stem cells induced by fluid shear stress. Biomech Model Mechanobiol 9: 659–670CrossRefGoogle Scholar
  25. McAllister TN, Du T, Frangos JA (2000) Fluid shear stress stimulates prostaglandin and nitric oxide release in bone marrow-derived preosteoclast-like cells. Biochem Biophys Res Commun 270: 643–648CrossRefGoogle Scholar
  26. Pavlin D, Dove SB, Zadro R, Gluhak-Heinrich J (2000) Mechanical loading stimulates differentiation of periodontal osteoblasts in a mouse osteoinduction model: effect on type I collagen and alkaline phosphatase genes. Calcif Tissue Int 67: 163–172CrossRefGoogle Scholar
  27. Rangaswami H, Marathe N, Zhuang S, Chen Y, Yeh JC, Frangos JA, Boss GR, Pilz RB (2009) Type II cGMP-dependent protein kinase mediates osteoblast mechanotransduction. J Biol Chem 284: 14796–14808CrossRefGoogle Scholar
  28. Riddle RC, Taylor AF, Genetos DC, Donahue HJ (2006) MAP kinase and calcium signaling mediate fluid flow-induced human mesenchymal stem cell proliferation. Am J Physiol Cell Physiol 290: C776–C784CrossRefGoogle Scholar
  29. Sharp LA, Lee YW, Goldstein AS (2009) Effect of low-frequency pulsatile flow on expression of osteoblastic genes by bone marrow stromal cells. Ann Biomed Eng 37: 445–453CrossRefGoogle Scholar
  30. Simmons CA, Matlis S, Thornton AJ, Chen S, Wang CY, Mooney DJ (2003) Cyclic strain enhances matrix mineralization by adult human mesenchymal stem cells via the extracellular signal- regulated kinase (ERK1/2) signaling pathway. J Biomech 36: 1087–1096CrossRefGoogle Scholar
  31. Stephens JS, Cooper JA, Phelan FR Jr, Dunkers JP (2007) Perfusion flow bioreactor for 3D in situ imaging: investigating cell/biomaterials interactions. Biotechnol Bioeng 97: 952–961CrossRefGoogle Scholar
  32. Stiehler M, Bunger C, Baatrup A, Lind M, Kassem M, Mygind T (2009) Effect of dynamic 3-D culture on proliferation, distribution, and osteogenic differentiation of human mesenchymal stem cells. J Biomed Mater Res A 89: 96–107Google Scholar
  33. Tanaka S, Matsuzaka K, Sato D, Inoue T (2007) Characteristics of newly formed bone during guided bone regeneration: analysis of cbfa-1, osteocalcin, and VEGF expression. J Oral Implantol 33: 321–326CrossRefGoogle Scholar
  34. Wang W, Li B, Li Y, Jiang Y, Ouyang H, Gao C (2010) In vivo restoration of full-thickness cartilage defects by poly(lactide-co- glycolide) sponges filled with fibrin gel, bone marrow mesenchymal stem cells and DNA complexes. Biomaterials 31: 5953–5965CrossRefGoogle Scholar
  35. Weinbaum S, Cowin SC, Zeng Y (1994) A model for the excitation of osteocytes by mechanical loading-induced bone fluid shear stresses. J Biomech 27: 339–360CrossRefGoogle Scholar
  36. Winter LC, Walboomers XF, Bumgardner JD, Jansen JA (2003) Intermittent versus continuous stretching effects on osteoblast-like cells in vitro. J Biomed Mater Res A 67: 1269–1275CrossRefGoogle Scholar
  37. Xiao G, Jiang D, Thomas P, Benson MD, Guan K, Karsenty G, Franceschi RT (2000) MAPK pathways activate and phosphorylate the osteoblast-specific transcription factor, Cbfa1. J Biol Chem 275: 4453–4459CrossRefGoogle Scholar
  38. Yang J, Cao C, Wang W, Tong X, Shi D, Wu F, Zheng Q, Guo C, Pan Z, Gao C, Wang J (2010) Proliferation and osteogenesis of immortalized bone marrow-derived mesenchymal stem cells in porous polylactic glycolic acid scaffolds under perfusion culture. J Biomed Mater Res A 92: 817–829Google Scholar
  39. Young SR, Gerard-O’Riley R, Kim JB, Pavalko FM (2009) Focal adhesion kinase is important for fluid shear stress-induced mechanotransduction in osteoblasts. J Bone Miner Res 24: 411–424CrossRefGoogle Scholar
  40. Yourek G, McCormick SM, Mao JJ, Reilly GC (2010) Shear stress induces osteogenic differentiation of human mesenchymal stem cells. Regen Med 5: 713–724CrossRefGoogle Scholar
  41. Zhang L, Bewick M, Lafrenie RM (2002) Role of Raf-1 and FAK in cell density-dependent regulation of integrin-dependent activation of MAP kinase. Carcinogenesis 23: 1251–1258CrossRefGoogle Scholar
  42. Zhao H, Ma L, Gao C, Shen J (2009) A composite scaffold of PLGA microspheres/fibrin gel for cartilage tissue engineering: fabrication, physical properties, and cell responsiveness. J Biomed Mater Res B Appl Biomater 88: 240–249Google Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Liyue Liu
    • 1
  • Bin Yu
    • 1
  • Jiarong Chen
    • 1
  • Zihua Tang
    • 1
  • Chen Zong
    • 1
  • Dan Shen
    • 3
  • Qiang Zheng
    • 4
  • Xiangming Tong
    • 3
  • Changyou Gao
    • 2
  • Jinfu Wang
    • 1
  1. 1.Institute of Cell Biology, College of Life SciencesZhejiang UniversityHangzhouPeople’s Republic of China
  2. 2.Institute of Medical Materials, College of Material and ChemistryZhejiang UniversityHangzhou, ZhejiangPeople’s Republic of China
  3. 3.Laboratory of Bone Marrow, The First HospitalZhejiang UniversityHangzhou, ZhejiangPeople’s Republic of China
  4. 4.Institute of Orthopedics, The Second HospitalZhejiang UniversityHangzhou, ZhejiangPeople’s Republic of China

Personalised recommendations