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.
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
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
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.
Michalak, Izabela
Department of Advanced Material Technologies, Faculty of Chemistry, Wrocław University of Science and Technology, Smoluchowskiego 25, 50-372, Wrocław, Poland.
Baouche, Meriem
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.
Kucharczyk, Katarzyna
Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Norwida 27B, 50-375, Wrocław, Poland.
Marycz, Krzysztof
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.
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.
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.
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.
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).
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.
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.
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.
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.
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.
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.
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.
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 N, Domagała J, Bourebaba L. Revitalizing equine metabolism: how SHBG improves mitochondrial function and reduces inflammation. BMC Vet Res 2025 Oct 21;21(1):620.
Ibrahim HAM, Hussein AM, Gabr M, El-Saeed RA, Ammar OA, Mosa AAH, Abdel-Aziz AF. Effect of Melatonin on Alpha Synuclein and Autophagy in Dopaminergic Neuronal Differentiation of Adipose Mesenchymal Stem Cells. Rep Biochem Mol Biol 2023 Apr;12(1):13-26.