Cladophora glomerata methanolic extract promotes chondrogenic gene expression and cartilage phenotype differentiation in equine adipose-derived mesenchymal stromal stem cells affected by metabolic syndrome.
Abstract: Chondrogenesis represents a highly dynamic cellular process that leads to the establishment of various types of cartilage. However, when stress-related injuries occur, a rapid and efficient regeneration of the tissues is necessary to maintain cartilage integrity. Mesenchymal stem cells (MSCs) are known to exhibit high capacity for self-renewal and pluripotency effects, and thus play a pivotal role in the repair and regeneration of damaged cartilage. On the other hand, the influence of certain pathological conditions such as metabolic disorders on MSCs can seriously impair their regenerative properties and thus reduce their therapeutic potential. In this investigation, we attempted to improve and potentiate the in vitro chondrogenic ability of adipose-derived mesenchymal stromal stem cells (ASCs) isolated from horses suffering from metabolic syndrome. Cultured cells in chondrogenic-inductive medium supplemented with Cladophora glomerata methanolic extract were experimented for expression of the main genes and microRNAs involved in the differentiation process using RT-PCR, for their morphological changes through confocal and scanning electron microscopy and for their physiological homeostasis. The different added concentrations of C. glomerata extract to the basic chondrogenic inductive culture medium promoted the proliferation of equine metabolic syndrome ASCs (ASCs) and resulted in chondrogenic phenotype differentiation and higher mRNA expression of collagen type II, aggrecan, cartilage oligomeric matrix protein, and Sox9 among others. The results reveal an obvious inhibitory effect of hypertrophy and a strong repression of miR-145-5p, miR-146-3p, and miR-34a and miR-449a largely involved in cartilage degradation. Treated cells additionally exhibited significant reduced apoptosis and oxidative stress, as well as promoted viability and mitochondrial potentiation. Chondrogenesis in EqASCs was found to be prominent after chondrogenic induction in conditions containing C. glomerata extract, suggesting that the macroalgae could be considered for the enhancement of ASC cultures and their reparative properties.
Publication Date: 2019-12-17 PubMed ID: 31847882PubMed Central: PMC6916455DOI: 10.1186/s13287-019-1499-zGoogle Scholar: Lookup
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Summary
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This study focuses on how an extract from the algae Cladophora glomerata can significantly enhance the ability of stem cells derived from the fat of horses with metabolic syndrome to develop into cartilage cells.
Overview of the Research
- The research revolves around understanding how chondrogenesis; a process involving the development of cartilage, can be influenced by the extract of Cladophora glomerata, a type of macroalgae. The researchers focus on the potential application of the algae extract in supporting the regeneration of cartilage in horses with metabolic syndrome.
- As the authors outline, the maintenance of cartilage integrity is especially critical when stress-related injuries occur. As a fundamental part of this process, the functionality of mesenchymal stem cells (MSCs) – which are known for their high capacity for self-renewal and pluripotency – is central. However, this functionality can be negatively affected by pathological conditions such as metabolic disorders.
- This study specifically focuses on fat-derived mesenchymal stromal stem cells (ASCs) isolated from horses suffering from metabolic syndrome, and seeks to enhance their in-vitro chondrogenic ability through the application of Cladophora glomerata, a kind of macroalgae, extract.
- The cultured cells were given chondrogenic-inductive media, supplemented with the extract, in order to promote cartilage development.
Findings of the Research
- The researchers found that the addition of different concentrations of the C. glomerata extract promoted the proliferation of ASCs, resulting in an acceleration of the differentiation into cartilage phenotypes (cell characteristics) and an increase in the expression of cartilage-specific genes such as collagen type II and aggrecan.
- The extract also showed an inhibitory effect on hypertrophy – an increase in the size of cells which can lead to damage – and significantly repressed the expression of certain microRNAs (small regulatory RNAs) known to be involved in cartilage degradation.
- In addition to these positive effects on chondrogenesis, the treated stem cells also displayed reduced rates of apoptosis (programmed cell death) and oxidative stress, showing enhanced cellular health and demonstrating increased viability and mitochondrial potentiation (strengthening or increasing of the action of mitochondria).
- In conclusion, the researchers found that Cladophora glomerata extract has the potential to enhance the reparative properties of ASCs, thus opening new possibilities in the application of this macroalgae extract in regenerative medicine, specifically in the domain of cartilage regeneration.
Cite This Article
APA
Bourebaba L, Michalak I, Baouche M, Kucharczyk K, Marycz K.
(2019).
Cladophora glomerata methanolic extract promotes chondrogenic gene expression and cartilage phenotype differentiation in equine adipose-derived mesenchymal stromal stem cells affected by metabolic syndrome.
Stem Cell Res Ther, 10(1), 392.
https://doi.org/10.1186/s13287-019-1499-z Publication
Researcher Affiliations
- Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Norwida 27B, 50-375, Wrocław, Poland.
- International Institute of Translational Medicine, Jesionowa, 11, Wisznia Mała, 55-114, Malin, Poland.
- Department of Advanced Material Technologies, Faculty of Chemistry, Wrocław University of Science and Technology, Smoluchowskiego 25, 50-372, Wrocław, Poland.
- Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Norwida 27B, 50-375, Wrocław, Poland.
- International Institute of Translational Medicine, Jesionowa, 11, Wisznia Mała, 55-114, Malin, Poland.
- Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Norwida 27B, 50-375, Wrocław, Poland.
- Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Norwida 27B, 50-375, Wrocław, Poland. krzysztof.marycz@upwr.edu.pl.
- International Institute of Translational Medicine, Jesionowa, 11, Wisznia Mała, 55-114, Malin, Poland. krzysztof.marycz@upwr.edu.pl.
- Collegium Medicum, Institute of Medical Science, Cardinal Stefan Wyszyński University (UKSW), Wóycickiego 1/3, 01-938, Warsaw, Poland. krzysztof.marycz@upwr.edu.pl.
MeSH Terms
- Aggrecans / genetics
- Aggrecans / metabolism
- Animals
- Apoptosis / drug effects
- Cell Differentiation / drug effects
- Chlorophyta / chemistry
- Chlorophyta / metabolism
- Chondrocytes / cytology
- Chondrocytes / metabolism
- Chondrogenesis / drug effects
- Collagen Type II / genetics
- Collagen Type II / metabolism
- Gene Expression / drug effects
- Horses
- Male
- Mesenchymal Stem Cells / cytology
- Mesenchymal Stem Cells / metabolism
- Metabolic Syndrome / metabolism
- Metabolic Syndrome / pathology
- MicroRNAs / metabolism
- Mitochondrial Membranes / drug effects
- Mitochondrial Membranes / physiology
- Plant Extracts / chemistry
- Plant Extracts / pharmacology
- Rats
- Rats, Sprague-Dawley
- Reactive Oxygen Species / metabolism
- SOX9 Transcription Factor / genetics
- SOX9 Transcription Factor / metabolism
Conflict of Interest Statement
The authors declare that they have no competing interests.
References
This article includes 56 references
- Cokelaere S, Malda J, van Weeren R. Cartilage defect repair in horses: Current strategies and recent developments in regenerative medicine of the equine joint with emphasis on the surgical approach.. Vet J 2016 Aug;214:61-71.
- Desjardins MR, Hurtig MB. Cartilage healing: A review with emphasis on the equine model.. Can Vet J 1990 Aug;31(8):565-72.
- Han Y, Lefebvre V. L-Sox5 and Sox6 drive expression of the aggrecan gene in cartilage by securing binding of Sox9 to a far-upstream enhancer.. Mol Cell Biol 2008 Aug;28(16):4999-5013.
- Wang M, Shen J, Jin H, Im HJ, Sandy J, Chen D. Recent progress in understanding molecular mechanisms of cartilage degeneration during osteoarthritis.. Ann N Y Acad Sci 2011 Dec;1240:61-9.
- Moffa AB, Ethier SP. Differential signal transduction of alternatively spliced FGFR2 variants expressed in human mammary epithelial cells.. J Cell Physiol 2007 Mar;210(3):720-31.
- Stanton H, Melrose J, Little CB, Fosang AJ. Proteoglycan degradation by the ADAMTS family of proteinases.. Biochim Biophys Acta 2011 Dec;1812(12):1616-29.
- Zhuo Q, Yang W, Chen J, Wang Y. Metabolic syndrome meets osteoarthritis.. Nat Rev Rheumatol 2012 Dec;8(12):729-37.
- Gregor MF, Hotamisligil GS. Inflammatory mechanisms in obesity.. Annu Rev Immunol 2011;29:415-45.
- Monteiro R, Azevedo I. Chronic inflammation in obesity and the metabolic syndrome.. Mediators Inflamm 2010;2010.
- Chen D, Shen J, Zhao W, Wang T, Han L, Hamilton JL, Im HJ. Osteoarthritis: toward a comprehensive understanding of pathological mechanism.. Bone Res 2017;5:16044.
- Kalamegam G, Memic A, Budd E, Abbas M, Mobasheri A. A Comprehensive Review of Stem Cells for Cartilage Regeneration in Osteoarthritis.. Adv Exp Med Biol 2018;1089:23-36.
- Pearle AD, Warren RF, Rodeo SA. Basic science of articular cartilage and osteoarthritis.. Clin Sports Med 2005 Jan;24(1):1-12.
- Lee PT, Li WJ. Chondrogenesis of Embryonic Stem Cell-Derived Mesenchymal Stem Cells Induced by TGFβ1 and BMP7 Through Increased TGFβ Receptor Expression and Endogenous TGFβ1 Production.. J Cell Biochem 2017 Jan;118(1):172-181.
- Lo Monaco M, Merckx G, Ratajczak J, Gervois P, Hilkens P, Clegg P, Bronckaers A, Vandeweerd JM, Lambrichts I. Stem Cells for Cartilage Repair: Preclinical Studies and Insights in Translational Animal Models and Outcome Measures.. Stem Cells Int 2018;2018:9079538.
- Baldari S, Di Rocco G, Piccoli M, Pozzobon M, Muraca M, Toietta G. Challenges and Strategies for Improving the Regenerative Effects of Mesenchymal Stromal Cell-Based Therapies.. Int J Mol Sci 2017 Oct 2;18(10).
- Dimmeler S, Leri A. Aging and disease as modifiers of efficacy of cell therapy.. Circ Res 2008 Jun 6;102(11):1319-30.
- Marycz K, Kornicka K, Szlapka-Kosarzewska J, Weiss C. Excessive Endoplasmic Reticulum Stress Correlates with Impaired Mitochondrial Dynamics, Mitophagy and Apoptosis, in Liver and Adipose Tissue, but Not in Muscles in EMS Horses.. Int J Mol Sci 2018 Jan 6;19(1).
- Kornicka K, Houston J, Marycz K. Dysfunction of Mesenchymal Stem Cells Isolated from Metabolic Syndrome and Type 2 Diabetic Patients as Result of Oxidative Stress and Autophagy may Limit Their Potential Therapeutic Use.. Stem Cell Rev Rep 2018 Jun;14(3):337-345.
- Marycz K, Michalak I, Kocherova I, Marędziak M, Weiss C. The Cladophora glomerata Enriched by Biosorption Process in Cr(III) Improves Viability, and Reduces Oxidative Stress and Apoptosis in Equine Metabolic Syndrome Derived Adipose Mesenchymal Stromal Stem Cells (ASCs) and Their Extracellular Vesicles (MV's).. Mar Drugs 2017 Dec 8;15(12).
- Marycz K, Kornicka K, Basinska K, Czyrek A. Equine Metabolic Syndrome Affects Viability, Senescence, and Stress Factors of Equine Adipose-Derived Mesenchymal Stromal Stem Cells: New Insight into EqASCs Isolated from EMS Horses in the Context of Their Aging.. Oxid Med Cell Longev 2016;2016:4710326.
- Nawrocka D, Kornicka K, Śmieszek A, Marycz K. Spirulina platensis Improves Mitochondrial Function Impaired by Elevated Oxidative Stress in Adipose-Derived Mesenchymal Stromal Cells (ASCs) and Intestinal Epithelial Cells (IECs), and Enhances Insulin Sensitivity in Equine Metabolic Syndrome (EMS) Horses.. Mar Drugs 2017 Aug 3;15(8).
- Marycz K, Weiss C, Śmieszek A, Kornicka K. Evaluation of Oxidative Stress and Mitophagy during Adipogenic Differentiation of Adipose-Derived Stem Cells Isolated from Equine Metabolic Syndrome (EMS) Horses.. Stem Cells Int 2018;2018:5340756.
- Marycz K, Kornicka K, Marędziak M, Golonka P, Nicpoń J. Equine metabolic syndrome impairs adipose stem cells osteogenic differentiation by predominance of autophagy over selective mitophagy.. J Cell Mol Med 2016 Dec;20(12):2384-2404.
- Udalamaththa VL, Jayasinghe CD, Udagama PV. Potential role of herbal remedies in stem cell therapy: proliferation and differentiation of human mesenchymal stromal cells.. Stem Cell Res Ther 2016 Aug 11;7(1):110.
- Sabeena Farvin KH, Jacobsen C. Phenolic compounds and antioxidant activities of selected species of seaweeds from Danish coast.. Food Chem 2013 Jun 1;138(2-3):1670-81.
- Srimaroeng C, Ontawong A, Saowakon N, Vivithanaporn P, Pongchaidecha A, Amornlerdpison D, Soodvilai S, Chatsudthipong V. Antidiabetic and renoprotective effects of Cladophora glomerata Kützing extract in experimental type 2 diabetic rats: a potential nutraceutical product for diabetic nephropathy.. J Diabetes Res 2015;2015:320167.
- Bourebaba L, Michalak I, Röcken M, Marycz K. Cladophora glomerata methanolic extract decreases oxidative stress and improves viability and mitochondrial potential in equine adipose derived mesenchymal stem cells (ASCs).. Biomed Pharmacother 2019 Mar;111:6-18.
- Hudson JB, Kim JH, Lee MK, DeWreede RE, Hong YK. Antiviral compounds in extracts of Korean seaweeds: evidence for multiple activities. J Appl Phycol 1998;10(5):427–434.
- Suszynska M, Poniewierska-Baran A, Gunjal P, Ratajczak J, Marycz K, Kakar SS, Kucia M, Ratajczak MZ. Expression of the erythropoietin receptor by germline-derived cells - further support for a potential developmental link between the germline and hematopoiesis.. J Ovarian Res 2014;7:66.
- Wang CY, Chen LL, Kuo PY, Chang JL, Wang YJ, Hung SC. Apoptosis in chondrogenesis of human mesenchymal stem cells: effect of serum and medium supplements.. Apoptosis 2010 Apr;15(4):439-49.
- Cooper KL, Oh S, Sung Y, Dasari RR, Kirschner MW, Tabin CJ. Multiple phases of chondrocyte enlargement underlie differences in skeletal proportions.. Nature 2013 Mar 21;495(7441):375-8.
- Akiyama H, Chaboissier MC, Martin JF, Schedl A, de Crombrugghe B. The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6.. Genes Dev 2002 Nov 1;16(21):2813-28.
- Zwickl H, Niculescu-Morzsa E, Halbwirth F, Bauer C, Jeyakumar V, Reutterer A, Berger M, Nehrer S. Correlation Analysis of SOX9, -5, and -6 as well as COL2A1 and Aggrecan Gene Expression of Collagen I Implant-Derived and Osteoarthritic Chondrocytes.. Cartilage 2016 Apr;7(2):185-92.
- Maldonado M, Nam J. The role of changes in extracellular matrix of cartilage in the presence of inflammation on the pathology of osteoarthritis.. Biomed Res Int 2013;2013:284873.
- Wang L, Huang J, Jiang M, Diao H, Zhou H, Li X, Chen Q, Jiang Z, Feng H, Wolfl S. Cartilage oligomeric matrix protein (COMP)-mediated cell differentiation to proteolysis mechanism networks from human normal adjacent tissues to lung adenocarcinoma.. Anal Cell Pathol (Amst) 2013;36(3-4):93-105.
- Strong AL, Gimble JM, Bunnell BA. Analysis of the Pro- and Anti-Inflammatory Cytokines Secreted by Adult Stem Cells during Differentiation.. Stem Cells Int 2015;2015:412467.
- Oh CD, Lu Y, Liang S, Mori-Akiyama Y, Chen D, de Crombrugghe B, Yasuda H. SOX9 regulates multiple genes in chondrocytes, including genes encoding ECM proteins, ECM modification enzymes, receptors, and transporters.. PLoS One 2014;9(9):e107577.
- Gris D, Ye Z, Iocca HA, Wen H, Craven RR, Gris P, Huang M, Schneider M, Miller SD, Ting JP. NLRP3 plays a critical role in the development of experimental autoimmune encephalomyelitis by mediating Th1 and Th17 responses.. J Immunol 2010 Jul 15;185(2):974-81.
- Papaioannou G, Mirzamohammadi F, Lisse TS, Nishimori S, Wein MN, Kobayashi T. MicroRNA-140 Provides Robustness to the Regulation of Hypertrophic Chondrocyte Differentiation by the PTHrP-HDAC4 Pathway.. J Bone Miner Res 2015 Jun;30(6):1044-52.
- Xu J, Lv S, Hou Y, Xu K, Sun D, Zheng Y, Zhang Z, Li X, Li Y, Chi G. miR-27b promotes type II collagen expression by targetting peroxisome proliferator-activated receptor-γ2 during rat articular chondrocyte differentiation.. Biosci Rep 2018 Feb 28;38(1).
- Zhong L, Huang X, Karperien M, Post JN. The Regulatory Role of Signaling Crosstalk in Hypertrophy of MSCs and Human Articular Chondrocytes.. Int J Mol Sci 2015 Aug 14;16(8):19225-47.
- Selvamurugan N, Jefcoat SC, Kwok S, Kowalewski R, Tamasi JA, Partridge NC. Overexpression of Runx2 directed by the matrix metalloproteinase-13 promoter containing the AP-1 and Runx/RD/Cbfa sites alters bone remodeling in vivo.. J Cell Biochem 2006 Oct 1;99(2):545-57.
- Lu H, Lin Z, Yang Z, Chen M, Zhang K. Inhibition of RUNX2 expression promotes differentiation of MSCs correlated with SDF-1 up-regulation in rats. Int J Clin Exp Pathol 2016;9(11):11388–11395.
- Yang B, Guo H, Zhang Y, Chen L, Ying D, Dong S. MicroRNA-145 regulates chondrogenic differentiation of mesenchymal stem cells by targeting Sox9.. PLoS One 2011;6(7):e21679.
- Paik S, Jung HS, Lee S, Yoon DS, Park MS, Lee JW. miR-449a regulates the chondrogenesis of human mesenchymal stem cells through direct targeting of lymphoid enhancer-binding factor-1.. Stem Cells Dev 2012 Dec 10;21(18):3298-308.
- Ahmed S. Green tea polyphenol epigallocatechin 3-gallate in arthritis: progress and promise.. Arthritis Res Ther 2010;12(2):208.
- Khanna D, Sethi G, Ahn KS, Pandey MK, Kunnumakkara AB, Sung B, Aggarwal A, Aggarwal BB. Natural products as a gold mine for arthritis treatment.. Curr Opin Pharmacol 2007 Jun;7(3):344-51.
- Thirunavukkarasu K, Pei Y, Moore TL, Wang H, Yu XP, Geiser AG, Chandrasekhar S. Regulation of the human ADAMTS-4 promoter by transcription factors and cytokines.. Biochem Biophys Res Commun 2006 Jun 23;345(1):197-204.
- Khalifé S, Zafarullah M. Molecular targets of natural health products in arthritis.. Arthritis Res Ther 2011 Feb 3;13(1):102.
- Blanco FJ, Guitian R, Vázquez-Martul E, de Toro FJ, Galdo F. Osteoarthritis chondrocytes die by apoptosis. A possible pathway for osteoarthritis pathology.. Arthritis Rheum 1998 Feb;41(2):284-9.
- Gerber HP, Vu TH, Ryan AM, Kowalski J, Werb Z, Ferrara N. VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation.. Nat Med 1999 Jun;5(6):623-8.
- Miyaki S, Asahara H. Macro view of microRNA function in osteoarthritis.. Nat Rev Rheumatol 2012 Sep;8(9):543-52.
- Jin L, Zhao J, Jing W, Yan S, Wang X, Xiao C, Ma B. Role of miR-146a in human chondrocyte apoptosis in response to mechanical pressure injury in vitro.. Int J Mol Med 2014 Aug;34(2):451-63.
- Ruiz-Romero C, Calamia V, Mateos J, Carreira V, Martínez-Gomariz M, Fernández M, Blanco FJ. Mitochondrial dysregulation of osteoarthritic human articular chondrocytes analyzed by proteomics: a decrease in mitochondrial superoxide dismutase points to a redox imbalance.. Mol Cell Proteomics 2009 Jan;8(1):172-89.
- Blanco FJ, López-Armada MJ, Maneiro E. Mitochondrial dysfunction in osteoarthritis.. Mitochondrion 2004 Sep;4(5-6):715-28.
- Regan E, Flannelly J, Bowler R, Tran K, Nicks M, Carbone BD, Glueck D, Heijnen H, Mason R, Crapo J. Extracellular superoxide dismutase and oxidant damage in osteoarthritis.. Arthritis Rheum 2005 Nov;52(11):3479-91.
Citations
This article has been cited 6 times.- Bourebaba N, Sikora M, Qasem B, Bourebaba L, Marycz K. Sex hormone-binding globulin (SHBG) mitigates ER stress and improves viability and insulin sensitivity in adipose-derived mesenchymal stem cells (ASC) of equine metabolic syndrome (EMS)-affected horses.. Cell Commun Signal 2023 Sep 11;21(1):230.
- Svoradová A, Vašíček J, Zmrhal V, Venusová E, Pavlík A, Bauer M, Olexiková L, Langraf V, Sláma P, Chrenek P. Mesenchymal stem cells of Oravka chicken breed: promising path to biodiversity conservation.. Poult Sci 2023 Aug;102(8):102807.
- Marycz K, Bourebaba N, Serwotka-Suszczak A, Mularczyk M, Galuppo L, Bourebaba L. In Vitro Generated Equine Hepatic-Like Progenitor Cells as a Novel Potent Cell Pool for Equine Metabolic Syndrome (EMS) Treatment.. Stem Cell Rev Rep 2023 May;19(4):1124-1134.
- Yosri M, Elaasser MM, Abdel-Aziz MM, Hassan MM, Alqhtani AH, Al-Gabri N, Ali ABA, Pokoo-Aikins A, Amin BH. Determination of Therapeutic and Safety Effects of Zygophyllum coccineum Extract in Induced Inflammation in Rats.. Biomed Res Int 2022;2022:7513155.
- Tirpáková M, Vašíček J, Svoradová A, Baláži A, Tomka M, Bauer M, Makarevich A, Chrenek P. Phenotypical Characterization and Neurogenic Differentiation of Rabbit Adipose Tissue-Derived Mesenchymal Stem Cells.. Genes (Basel) 2021 Mar 17;12(3).
- Bourebaba L, Kornicka-Garbowska K, Al Naem M, Röcken M, Łyczko J, Marycz K. MSI-1436 improves EMS adipose derived progenitor stem cells in the course of adipogenic differentiation through modulation of ER stress, apoptosis, and oxidative stress.. Stem Cell Res Ther 2021 Feb 3;12(1):97.
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