The osmolyte type affects cartilage associated pathologic marker expression during in vitro mesenchymal stem cell chondrogenesis under hypertonic conditions

Sorour Ahmadyan; Mahboubeh Kabiri; Noushin Tasharofi; Simzar Hosseinzadeh; Mousa Kehtari; Athena Hajari Zadeh; Masoud Soleimani; Ali Farazmand; Hana Hanaee-Ahvaz

doi:10.14715/cmb/2018.64.3.10

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Vol. 64 No. 3: Issue 3

Issue Published : March 3, 2018

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The osmolyte type affects cartilage associated pathologic marker expression during in vitro mesenchymal stem cell chondrogenesis under hypertonic conditions

https://doi.org/10.14715/cmb/2018.64.3.10

Sorour Ahmadyan

Department of Biotechnology, College of science, University of Tehran, Tehran, Iran

Mahboubeh Kabiri

Department of Biotechnology, College of science, University of Tehran, Tehran, Iran

Noushin Tasharofi

Stem Cell Technology Research Center, Tehran, Iran

Simzar Hosseinzadeh

Stem Cell Technology Research Center, Tehran, Iran

Mousa Kehtari

Faculty of Biology, University of Tehran, Tehran, Iran

Athena Hajari Zadeh

Stem Cell Technology Research Center, Tehran, Iran

Masoud Soleimani

Department of Hematology, Tarbiat Modares University, Tehran, Iran

Ali Farazmand

Faculty of Biology, University of Tehran, Tehran, Iran

Hana Hanaee-Ahvaz

Stem Cell Technology Research Center, Tehran, Iran

Corresponding Author(s) : Mahboubeh Kabiri

mkabiri@ut.ac.ir

Cellular and Molecular Biology, Vol. 64 No. 3: Issue 3
Article Published : February 28, 2018

Abstract

Stem cells' fate during in vitro differentiation is influenced by biophysicochemical cues. Osmotic stress has proved to enhance chondrocyte marker expression, however its potent negative impacts had never been surveyed. We questioned whether specific osmotic conditions, regarding the osmolyte agent, could benefit chondrogenesis while dampening undesired concomitant hypertrophy and inflammatory responses. To examine the potential side effects of hypertonicity, we assessed cell proliferation as well as chondrogenic and hypertrophic marker expression of human Adipose Derived-MSC after a two week induction in chondrogenic media with either NaCl or Sorbitol, as the osmolyte agent to reach a +100 mOsm hypertonic condition. Calcium deposition and TNF-Î± secretion as markers associated with hypertrophy and inflammation were then assayed. While both hyperosmotic conditions upregulated chondrogenic markers, sorbitol had a nearly three times higher chondro-promotive effect and a lesser hypertrophic effect compared to NaCl. Also, a significantly lesser calcium deposition was observed in sorbitol hypertonic group. NaCl showed an anti-proinflammatory effect while sorbitol had no effect on inflammatory markers. The ossification potential and cartilage associated pathologic markers were affected differentially by the type of the osmolyte. Thus, a vigilant application of the osmotic agent is inevitable in order to avoid or reduce undesired hypertrophic and inflammatory phenotype acquisition by MSC during chondrogenic differentiation. Our findings are a step towards developing a more reliable chondrogenic regimen using external hypertonic cues for MSC chondrogenesis with potential applications in chondral lesions cell therapy.

Keywords

Hypertonic stress Hypertrophy Inflammation MSC chondrogenesis Osmolyte.

Ahmadyan, S., Kabiri, M., Tasharofi, N., Hosseinzadeh, S., Kehtari, M., Hajari Zadeh, A., Soleimani, M., Farazmand, A., & Hanaee-Ahvaz, H. (2018). The osmolyte type affects cartilage associated pathologic marker expression during in vitro mesenchymal stem cell chondrogenesis under hypertonic conditions. Cellular and Molecular Biology, 64(3), 56–61. https://doi.org/10.14715/cmb/2018.64.3.10

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References

Caron MM, van der Windt AE, Emans PJ, van Rhijn LW, Jahr H, Welting TJ. Osmolarity determines the in vitro chondrogenic differentiation capacity of progenitor cells via nuclear factor of activated T-cells 5. Bone 2013; 53(1): 94-102.
Osiecki MJ, Michl TD, Kul Babur B et al. Packed Bed Bioreactor for the Isolation and Expansion of Placental-Derived Mesenchymal Stromal Cells. PLoS One 2015; 10(12): e0144941.
Shafiee A, Kabiri M, Langroudi L, Soleimani M, Ai J. Evaluation and comparison of the in vitro characteristics and chondrogenic capacity of four adult stem/progenitor cells for cartilage cell-based repair. J Biomed Mater Res A Oct 27 2015.
Van der Kraan P, Van den Berg W. Chondrocyte hypertrophy and osteoarthritis: role in initiation and progression of cartilage degeneration? Osteoarthritis and Cartilage 2012; 20(3): 223-232.
Ramezanifard R, Kabiri M, Hanaee Ahvaz H. Effects of platelet rich plasma and chondrocyte co-culture on MSC chondrogenesis, hypertrophy and pathological responses. EXCLI J 2017; 16: 1031-1045.
Jahr H, Matta C, Mobasheri A. Physicochemical and biomechanical stimuli in cell-based articular cartilage repair. Current rheumatology reports 2015; 17(3): 1-12.
van der Windt AE, Haak E, Das RH et al. Physiological tonicity improves human chondrogenic marker expression through nuclear factor of activated T-cells 5 in vitro. Arthritis research & therapy 2010; 12(3): 1.
Bertram KL, Krawetz RJ. Osmolarity regulates chondrogenic differentiation potential of synovial fluid derived mesenchymal progenitor cells. Biochem Biophys Res Commun Jun 08 2012; 422(3): 455-461.
Neuhofer W. Role of NFAT5 in inflammatory disorders associated with osmotic stress. Current genomics 2010; 11(8): 584-590.
Park J-O, Lee BH, Kang Y-M et al. Inflammatory cytokines induce fibrosis and ossification of human ligamentum flavum cells. Clinical Spine Surgery 2013; 26(1): E6-E12.
Urban J, Hall A, Gehl K. Regulation of matrix synthesis rates by the ionic and osmotic environment of articular chondrocytes. J Cell Physiol 1993; 154(2): 262-270.
Dodel M, Hemmati Nejad N, Bahrami SH et al. Electrical stimulation of somatic human stem cells mediated by composite containing conductive nanofibers for ligament regeneration. Biologicals Mar 2017; 46: 99-107.
Kabiri M, Oraee-Yazdani S, Dodel M et al. Cytocompatibility of a conductive nanofibrous carbon nanotube/poly (L-Lactic acid) composite scaffold intended for nerve tissue engineering. EXCLI journal 2015; 14: 851.
Kabiri M, Kul B, Lott WB et al. 3D mesenchymal stem/stromal cell osteogenesis and autocrine signalling. Biochem Biophys Res Commun Mar 09 2012; 419(2): 142-147.
Babur BK, Kabiri M, Klein TJ, Lott WB, Doran MR. The rapid manufacture of uniform composite multicellular-biomaterial micropellets, their assembly into macroscopic organized tissues, and potential applications in cartilage tissue engineering. PLoS One 2015; 10(5): e0122250.
Lee CS, Burnsed OA, Raghuram V, Kalisvaart J, Boyan BD, Schwartz Z. Adipose stem cells can secrete angiogenic factors that inhibit hyaline cartilage regeneration. Stem cell research & therapy 2012; 3(4): 35.
Cancedda R, Castagnola P, Cancedda FD, Dozin B, Quarto R. Developmental control of chondrogenesis and osteogenesis. International Journal of Developmental Biology 2004; 44(6): 707-714.
Ahmadyan S, Kabiri M, Hanaee-Ahvaz H, Farazmand A. Osmolyte Type and the Osmolarity Level Affect Chondrogenesis of Mesenchymal Stem Cells. Appl Biochem Biotechnol Nov 10 2017.
Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier J-P, Fahmi H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nature Reviews Rheumatology 2011; 7(1): 33-42.
Discher DE, Mooney DJ, Zandstra PW. Growth factors, matrices, and forces combine and control stem cells. Science 2009; 324(5935): 1673-1677.
Ghanavi P, Kabiri M, Doran MR. The rationale for using microscopic units of a donor matrix in cartilage defect repair. Cell Tissue Res Mar 2012; 347(3): 643-648.
Cs"Szabó G, Roughley PJ, Plaas AH, Glant TT. Large and small proteoglycans of osteoarthritic and rheumatoid articular cartilage. Arthritis & Rheumatology 1995; 38(5): 660-668.
Li DQ, Chen Z, Song XJ, Luo L, Pflugfelder SC. Stimulation of matrix metalloproteinases by hyperosmolarity via a JNK pathway in human corneal epithelial cells. Invest Ophthalmol Vis Sci Dec 2004; 45(12): 4302-4311.
Le D, Hofbauer MA, Towle CA. Differential effects of hyperosmotic challenge on interleukin-1-activated pathways in bovine articular cartilage. Archives of biochemistry and biophysics 2006; 445(1): 1-8.
Rosette C, Karin M. Ultraviolet light and osmotic stress: activation of the JNK cascade through multiple growth factor and cytokine receptors. Science 1996; 274(5290): 1194.
Abolhassani M, Wertz X, Pooya M, Chaumet-Riffaud P, Guais A, Schwartz L. Hyperosmolarity causes inflammation through the methylation of protein phosphatase 2A. Inflammation Research 2008; 57(9): 419-429.
Obrosova IG. Increased sorbitol pathway activity generates oxidative stress in tissue sites for diabetic complications. Antioxidants & redox signaling 2005; 7(11-12): 1543-1552.
Hall AC, Horwitz ER, Wilkins RJ. The cellular physiology of articular cartilage. Experimental physiology 1996; 81(3): 535-545.
Hdud IM, Mobasheri A, Loughna PT. Effect of osmotic stress on the expression of TRPV4 and BKCa channels and possible interaction with ERK1/2 and p38 in cultured equine chondrocytes. American Journal of Physiology-Cell Physiology 2014; 306(11): C1050-C1057.

References

Caron MM, van der Windt AE, Emans PJ, van Rhijn LW, Jahr H, Welting TJ. Osmolarity determines the in vitro chondrogenic differentiation capacity of progenitor cells via nuclear factor of activated T-cells 5. Bone 2013; 53(1): 94-102.

Osiecki MJ, Michl TD, Kul Babur B et al. Packed Bed Bioreactor for the Isolation and Expansion of Placental-Derived Mesenchymal Stromal Cells. PLoS One 2015; 10(12): e0144941.

Shafiee A, Kabiri M, Langroudi L, Soleimani M, Ai J. Evaluation and comparison of the in vitro characteristics and chondrogenic capacity of four adult stem/progenitor cells for cartilage cell-based repair. J Biomed Mater Res A Oct 27 2015.

Van der Kraan P, Van den Berg W. Chondrocyte hypertrophy and osteoarthritis: role in initiation and progression of cartilage degeneration? Osteoarthritis and Cartilage 2012; 20(3): 223-232.

Ramezanifard R, Kabiri M, Hanaee Ahvaz H. Effects of platelet rich plasma and chondrocyte co-culture on MSC chondrogenesis, hypertrophy and pathological responses. EXCLI J 2017; 16: 1031-1045.

Jahr H, Matta C, Mobasheri A. Physicochemical and biomechanical stimuli in cell-based articular cartilage repair. Current rheumatology reports 2015; 17(3): 1-12.

van der Windt AE, Haak E, Das RH et al. Physiological tonicity improves human chondrogenic marker expression through nuclear factor of activated T-cells 5 in vitro. Arthritis research & therapy 2010; 12(3): 1.

Bertram KL, Krawetz RJ. Osmolarity regulates chondrogenic differentiation potential of synovial fluid derived mesenchymal progenitor cells. Biochem Biophys Res Commun Jun 08 2012; 422(3): 455-461.

Neuhofer W. Role of NFAT5 in inflammatory disorders associated with osmotic stress. Current genomics 2010; 11(8): 584-590.

Park J-O, Lee BH, Kang Y-M et al. Inflammatory cytokines induce fibrosis and ossification of human ligamentum flavum cells. Clinical Spine Surgery 2013; 26(1): E6-E12.

Urban J, Hall A, Gehl K. Regulation of matrix synthesis rates by the ionic and osmotic environment of articular chondrocytes. J Cell Physiol 1993; 154(2): 262-270.

Dodel M, Hemmati Nejad N, Bahrami SH et al. Electrical stimulation of somatic human stem cells mediated by composite containing conductive nanofibers for ligament regeneration. Biologicals Mar 2017; 46: 99-107.

Kabiri M, Oraee-Yazdani S, Dodel M et al. Cytocompatibility of a conductive nanofibrous carbon nanotube/poly (L-Lactic acid) composite scaffold intended for nerve tissue engineering. EXCLI journal 2015; 14: 851.

Kabiri M, Kul B, Lott WB et al. 3D mesenchymal stem/stromal cell osteogenesis and autocrine signalling. Biochem Biophys Res Commun Mar 09 2012; 419(2): 142-147.

Babur BK, Kabiri M, Klein TJ, Lott WB, Doran MR. The rapid manufacture of uniform composite multicellular-biomaterial micropellets, their assembly into macroscopic organized tissues, and potential applications in cartilage tissue engineering. PLoS One 2015; 10(5): e0122250.

Lee CS, Burnsed OA, Raghuram V, Kalisvaart J, Boyan BD, Schwartz Z. Adipose stem cells can secrete angiogenic factors that inhibit hyaline cartilage regeneration. Stem cell research & therapy 2012; 3(4): 35.

Cancedda R, Castagnola P, Cancedda FD, Dozin B, Quarto R. Developmental control of chondrogenesis and osteogenesis. International Journal of Developmental Biology 2004; 44(6): 707-714.

Ahmadyan S, Kabiri M, Hanaee-Ahvaz H, Farazmand A. Osmolyte Type and the Osmolarity Level Affect Chondrogenesis of Mesenchymal Stem Cells. Appl Biochem Biotechnol Nov 10 2017.

Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier J-P, Fahmi H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nature Reviews Rheumatology 2011; 7(1): 33-42.

Discher DE, Mooney DJ, Zandstra PW. Growth factors, matrices, and forces combine and control stem cells. Science 2009; 324(5935): 1673-1677.

Ghanavi P, Kabiri M, Doran MR. The rationale for using microscopic units of a donor matrix in cartilage defect repair. Cell Tissue Res Mar 2012; 347(3): 643-648.

Cs"Szabó G, Roughley PJ, Plaas AH, Glant TT. Large and small proteoglycans of osteoarthritic and rheumatoid articular cartilage. Arthritis & Rheumatology 1995; 38(5): 660-668.

Li DQ, Chen Z, Song XJ, Luo L, Pflugfelder SC. Stimulation of matrix metalloproteinases by hyperosmolarity via a JNK pathway in human corneal epithelial cells. Invest Ophthalmol Vis Sci Dec 2004; 45(12): 4302-4311.

Le D, Hofbauer MA, Towle CA. Differential effects of hyperosmotic challenge on interleukin-1-activated pathways in bovine articular cartilage. Archives of biochemistry and biophysics 2006; 445(1): 1-8.

Rosette C, Karin M. Ultraviolet light and osmotic stress: activation of the JNK cascade through multiple growth factor and cytokine receptors. Science 1996; 274(5290): 1194.

Abolhassani M, Wertz X, Pooya M, Chaumet-Riffaud P, Guais A, Schwartz L. Hyperosmolarity causes inflammation through the methylation of protein phosphatase 2A. Inflammation Research 2008; 57(9): 419-429.

Obrosova IG. Increased sorbitol pathway activity generates oxidative stress in tissue sites for diabetic complications. Antioxidants & redox signaling 2005; 7(11-12): 1543-1552.

Hall AC, Horwitz ER, Wilkins RJ. The cellular physiology of articular cartilage. Experimental physiology 1996; 81(3): 535-545.

Hdud IM, Mobasheri A, Loughna PT. Effect of osmotic stress on the expression of TRPV4 and BKCa channels and possible interaction with ERK1/2 and p38 in cultured equine chondrocytes. American Journal of Physiology-Cell Physiology 2014; 306(11): C1050-C1057.

Author biographies is not available.