Effects of the oral administration of glycosaminoglycans with or without native type II collagen on the articular cartilage transcriptome in an osteoarthritic-induced rabbit model.
Articular cartilage
Native type II collagen
Nutraceuticals
Osteoarthritis
Transcriptomics
Journal
Genes & nutrition
ISSN: 1555-8932
Titre abrégé: Genes Nutr
Pays: Germany
ID NLM: 101280108
Informations de publication
Date de publication:
04 Sep 2024
04 Sep 2024
Historique:
received:
02
04
2024
accepted:
30
07
2024
medline:
5
9
2024
pubmed:
5
9
2024
entrez:
4
9
2024
Statut:
epublish
Résumé
In a previous study, the 84-day administration of glycosaminoglycans (GAGs), with or without native collagen type II (NC), in an osteoarthritis (OA)-induced rabbit model slowed down OA progression, improved several micro- and macroscopic parameters and magnetic resonance imaging (MRI) biomarkers in cartilage, and increased hyaluronic acid levels in synovial fluid. To elucidate the potential underlying mechanisms, a transcriptomics approach was conducted using medial femoral condyle and trochlea samples. The administration of chondroitin sulfate (CS), glucosamine hydrochloride (GlHCl), and hyaluronic acid (HA), with (CGH-NC) or without (CGH) NC, strongly modulated several genes involved in chondrocyte extracellular matrix (ECM) remodeling and homeostasis when compared to non-treated rabbits (CTR group). Notably, both treatments shared the main mechanism of action, which was related to ECM modulation through the down-regulation of genes encoding proteolytic enzymes, such as ADAM metallopeptidase with thrombospondin type 1 motif, 9 (Adamts9), and the overexpression of genes with a relevant role in the synthesis of ECM components, such as aggrecan (Acan) in both CGH-NC and CGH groups, and fibronectin 1 (Fn1) and collagen type II, alpha 1 (Col2A1) in the CGH group. Furthermore, there was a significant modulation at the gene expression level of the mTOR signaling pathway, which is associated with the regulation of the synthesis of ECM proteolytic enzymes, only in CGH-NC-supplemented rabbits. This modulation could account for the better outcomes concerning the microscopic and macroscopic evaluations reported in these animals. In conclusion, the expression of key genes involved in chondrocyte ECM remodeling and homeostasis was significantly modulated in rabbits in response to both CGH and CGH-NC treatments, which would partly explain the mechanisms by which these therapies exert beneficial effects against OA.
Sections du résumé
BACKGROUND
BACKGROUND
In a previous study, the 84-day administration of glycosaminoglycans (GAGs), with or without native collagen type II (NC), in an osteoarthritis (OA)-induced rabbit model slowed down OA progression, improved several micro- and macroscopic parameters and magnetic resonance imaging (MRI) biomarkers in cartilage, and increased hyaluronic acid levels in synovial fluid. To elucidate the potential underlying mechanisms, a transcriptomics approach was conducted using medial femoral condyle and trochlea samples.
RESULTS
RESULTS
The administration of chondroitin sulfate (CS), glucosamine hydrochloride (GlHCl), and hyaluronic acid (HA), with (CGH-NC) or without (CGH) NC, strongly modulated several genes involved in chondrocyte extracellular matrix (ECM) remodeling and homeostasis when compared to non-treated rabbits (CTR group). Notably, both treatments shared the main mechanism of action, which was related to ECM modulation through the down-regulation of genes encoding proteolytic enzymes, such as ADAM metallopeptidase with thrombospondin type 1 motif, 9 (Adamts9), and the overexpression of genes with a relevant role in the synthesis of ECM components, such as aggrecan (Acan) in both CGH-NC and CGH groups, and fibronectin 1 (Fn1) and collagen type II, alpha 1 (Col2A1) in the CGH group. Furthermore, there was a significant modulation at the gene expression level of the mTOR signaling pathway, which is associated with the regulation of the synthesis of ECM proteolytic enzymes, only in CGH-NC-supplemented rabbits. This modulation could account for the better outcomes concerning the microscopic and macroscopic evaluations reported in these animals.
CONCLUSIONS
CONCLUSIONS
In conclusion, the expression of key genes involved in chondrocyte ECM remodeling and homeostasis was significantly modulated in rabbits in response to both CGH and CGH-NC treatments, which would partly explain the mechanisms by which these therapies exert beneficial effects against OA.
Identifiants
pubmed: 39232650
doi: 10.1186/s12263-024-00749-2
pii: 10.1186/s12263-024-00749-2
doi:
Types de publication
Journal Article
Langues
eng
Pagination
19Informations de copyright
© 2024. The Author(s).
Références
Jang S, Lee K, Ju JH. Recent updates of diagnosis, pathophysiology, and treatment on Osteoarthritis of the knee. Int J Mol Sci. 2021;22(5):1–15.
doi: 10.3390/ijms22052619
Kraus VB, Blanco FJ, Englund M, Karsdal MA, Lohmander LS. Call for standardized definitions of osteoarthritis and risk stratification for clinical trials and clinical use. Osteoarthritis Cartilage. 2015;23(8):1233–41.
doi: 10.1016/j.joca.2015.03.036
pubmed: 25865392
pmcid: 4516635
Martel-Pelletier J, Barr AJ, Cicuttini FM, Conaghan PG, Cooper C, Goldring MB et al. Osteoarthr Nat Rev Dis Primers. 2016;2.
Katz JN, Arant KR, Loeser RF. Diagnosis and treatment of hip and knee osteoarthritis: a review. JAMA. 2021;325(6):568–78.
doi: 10.1001/jama.2020.22171
pubmed: 33560326
pmcid: 8225295
Hochberg MC, Martel-Pelletier J, Monfort J, Möller I, Castillo JR, Arden N, et al. Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis: a multicentre, randomised, double-blind, non-inferiority trial versus celecoxib. Ann Rheum Dis. 2016;75(1):37–44.
doi: 10.1136/annrheumdis-2014-206792
pubmed: 25589511
Du Souich P. Absorption, distribution and mechanism of action of SYSADOAS. Pharmacol Ther. 2014;142(3):362–74.
doi: 10.1016/j.pharmthera.2014.01.002
pubmed: 24457028
Luo C, Su W, Song Y, Srivastava S. Efficacy and safety of native type II collagen in modulating knee osteoarthritis symptoms: a randomised, double-blind, placebo-controlled trial. J Exp Orthop. 2022;9(1):123.
doi: 10.1186/s40634-022-00559-8
pubmed: 36562843
pmcid: 9780623
Martínez-Puig D, Costa-Larrión E, Rubio-Rodríguez N, Gálvez-Martín P. Collagen Supplementation for Joint Health: the link between composition and scientific knowledge. Nutrients 2023. Page 1332. 2023;15(6):1332.
Di Cesare Mannelli L, Micheli L, Zanardelli M, Ghelardini C. Low dose native type II collagen prevents pain in a rat osteoarthritis model. BMC Musculoskelet Disord. 2013;14:228.
doi: 10.1186/1471-2474-14-228
pubmed: 23915264
pmcid: 3751133
Sifre V, Soler C, Segarra S, Redondo JI, Doménech L, Ten-Esteve A, et al. Improved Joint Health Following Oral Administration of Glycosaminoglycans with native type II collagen in a rabbit model of Osteoarthritis. Animals. 2022;12(11):1401.
doi: 10.3390/ani12111401
pubmed: 35681865
pmcid: 9179918
Liu W, Jiao Y, Tian C, Hasty K, Song L, Kelly DM, et al. Gene expression profiling studies using microarray in Osteoarthritis: genes in common and different conditions. Arch Immunol Ther Exp (Warsz). 2020;68(5):28.
doi: 10.1007/s00005-020-00592-4
pubmed: 32914280
Fan Q, Liu Z, Shen C, Li H, Ding J, Jin F, et al. Microarray study of gene expression profile to identify new candidate genes involved in the molecular mechanism of leptin-induced knee joint osteoarthritis in rat. Hereditas. 2018;155(1):4.
doi: 10.1186/s41065-017-0039-z
pubmed: 28690479
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2 – ∆∆CT method. Methods. 2001;25(4):402–8.
doi: 10.1006/meth.2001.1262
pubmed: 11846609
de Sire A, Marotta N, Marinaro C, Curci C, Invernizzi M, Ammendolia A. Role of Physical Exercise and Nutraceuticals in Modulating Molecular Pathways of Osteoarthritis. Int J Mol Sci. 2021 Jun 1;22(11).
Martinez-Silvestrini JA. Prescribing Medications for Pain and Inflammation. Clinical Sports Medicine: Medical Management and Rehabilitation, Text with CD-ROM. 2007;193–205.
Weiner HL. Oral tolerance for the treatment of autoimmune diseases. Annu Rev Med. 1997;48:341–51.
Altman RD, Manjoo A, Fierlinger A, Niazi F, Nicholls M. The mechanism of action for hyaluronic acid treatment in the osteoarthritic knee: a systematic review. BMC Musculoskelet Disord. 2015 Oct 26;16(1).
Martínez-Puig D, Costa-Larrión E, Rubio-Rodríguez N, Gálvez-Martín P. Collagen Supplementation for Joint Health: The Link between Composition and Scientific Knowledge. Nutrients. 2023 Mar 1;15(6).
Fernández-Torres J, Martínez-Nava GA, Gutiérrez-Ruíz MC, Gómez-Quiroz LE, Gutiérrez M. Role of HIF-1α signaling pathway in osteoarthritis: a systematic review. Rev Bras Reumatol. 2017;57(2):162–73.
Zeng CY, Wang XF, Hua FZ. HIF-1α in Osteoarthritis: from pathogenesis to therapeutic implications. Front Pharmacol. 2022;13:927126.
doi: 10.3389/fphar.2022.927126
pubmed: 35865944
pmcid: 9294386
Lian C, Wang X, Qiu X, Wu Z, Gao B, Liu L et al. Collagen type II suppresses articular chondrocyte hypertrophy and osteoarthritis progression by promoting integrin β1 – SMAD1 interaction. Bone Research 2019 7:1. 2019;7(1):1–15.
Martin JA, Buckwalter JA. Effects of fibronectin on articular cartilage chondrocyte proteoglycan synthesis and response to insulin-like growth factor-I. J Orthop Res. 1998;16(6):752–7.
doi: 10.1002/jor.1100160618
pubmed: 9877401
Burton-Wurster N, Lust G, MacLeod JN. Cartilage fibronectin isoforms: in search of functions for a special population of matrix glycoproteins. Matrix Biol. 1997;15(7):441–54.
doi: 10.1016/S0945-053X(97)90018-4
pubmed: 9106156
Park EJ, Myint PK, Ito A, Appiah MG, Darkwah S, Kawamoto E, et al. Integrin-ligand interactions in inflammation, Cancer, and metabolic disease: insights into the multifaceted roles of an emerging Ligand Irisin. Front Cell Dev Biol. 2020;8:1196.
doi: 10.3389/fcell.2020.588066
Alcaide-Ruggiero L, Molina-Hernández V, Granados MM, Domínguez JM. Main and minor types of Collagens in the articular cartilage: the role of Collagens in Repair tissue evaluation in Chondral defects. Int J Mol Sci. 2021;22(24):13329.
doi: 10.3390/ijms222413329
pubmed: 34948124
pmcid: 8706311
Poonpet T, Honsawek S, Adipokines. Biomarkers for osteoarthritis? World J Orthop. 2014;5(3):319.
doi: 10.5312/wjo.v5.i3.319
pubmed: 25035835
pmcid: 4095025
Kang EH, Lee YJ, Kim TK, Chang CB, Chung JH, Shin K, et al. Adiponectin is a potential catabolic mediator in osteoarthritis cartilage. Arthritis Res Ther. 2010;12(6):1–11.
doi: 10.1186/ar3218
Gratchev A, Schmuttermaier C, Mamidi S, Gooi LM, Goerdt S, Kzhyshkowska J. Expression of osteoarthritis marker YKL-39 is stimulated by transforming growth factor Beta (TGF-beta) and IL-4 in differentiating macrophages. Biomark Insights. 2008;3(3):39.
pubmed: 19578492
pmcid: 2688341
Knorr T, Obermayr F, Bartnik E, Zien A, Aigner T. YKL-39 (chitinase 3-like protein 2), but not YKL-40 (chitinase 3-like protein 1), is up regulated in osteoarthritic chondrocytes. Ann Rheum Dis. 2003;62(10):995–8.
doi: 10.1136/ard.62.10.995
pubmed: 12972480
pmcid: 1754335
Huang K, Wu LD. Aggrecanase and aggrecan degradation in osteoarthritis: a review. J Int Med Res. 2008;36(6):1149–60.
doi: 10.1177/147323000803600601
pubmed: 19094423
Kobayashi K, Matsuzaka S, Yoshida Y, Miyauchi S, Wada Y, Moriya H. The effects of intraarticularly injected sodium hyaluronate on levels of intact aggrecan and nitric oxide in the joint fluid of patients with knee osteoarthritis. Osteoarthritis Cartilage. 2004;12(7):536–42.
doi: 10.1016/j.joca.2004.03.005
pubmed: 15219568
Mokuda S, Nakamichi R, Matsuzaki T, Ito Y, Sato T, Miyata K et al. Wwp2 maintains cartilage homeostasis through regulation of Adamts5. Nat Commun. 2019;10(1).
Terencio MC, Ferrándiz ML, Carceller MC, Ruhí R, Dalmau P, Vergés J et al. Chondroprotective effects of the combination chondroitin sulfate-glucosamine in a model of osteoarthritis induced by anterior cruciate ligament transection in ovariectomised rats. Biomed Pharmacother. 2016 Apr 1;79:120–8.
Lei J, Amhare AF, Wang L, Lv Y, Deng H, Gao H et al. Proteomic analysis of knee cartilage reveals potential signaling pathways in pathological mechanism of Kashin-Beck disease compared with osteoarthritis. Scientific Reports 2020 10:1. 2020;10(1):1–11.
Loeser RF. Integrins and chondrocyte-matrix interactions in articular cartilage. Matrix Biol. 2014;39:11–6.
doi: 10.1016/j.matbio.2014.08.007
pubmed: 25169886
pmcid: 4699681
Jin H, Jiang S, Wang R, Zhang Y, Dong J, Li Y. Mechanistic insight into the roles of integrins in Osteoarthritis. Front Cell Dev Biol. 2021;9:1518.
doi: 10.3389/fcell.2021.693484
Ripmeester EGJ, Timur UT, Caron MMJ, Welting TJM. Recent insights into the contribution of the changing hypertrophic chondrocyte phenotype in the development and progression of osteoarthritis. Front Bioeng Biotechnol. 2018;6(MAR):18.
doi: 10.3389/fbioe.2018.00018
pubmed: 29616218
pmcid: 5867295
Becerril MA, Roselló MC, Kouri J. Changes in the chondrocyte-extracellular matrix relationship during OA pathogenesistle. Osteoarthritis Cartilage. 2016;24(1):S155.
doi: 10.1016/j.joca.2016.01.306
Castaño Betancourt MC, Cailotto F, Kerkhof HJ, Cornelis FMF, Doherty SA, Hart DJ, et al. Genome-wide association and functional studies identify the DOT1L gene to be involved in cartilage thickness and hip osteoarthritis. Proc Natl Acad Sci U S A. 2012;109(21):8218–23.
doi: 10.1073/pnas.1119899109
pubmed: 22566624
pmcid: 3361426
Zemmyo M, Meharra EJ, Kühn K, Creighton-Achermann L, Lotz M. Accelerated, aging-dependent development of osteoarthritis in alpha1 integrin-deficient mice. Arthritis Rheum. 2003;48(10):2873–80.
doi: 10.1002/art.11246
pubmed: 14558093
Pfander D, Cramer T, Deuerling D, Weseloh G, Swoboda B. Expression of thrombospondin-1 and its receptor CD36 in human osteoarthritic cartilage. Ann Rheum Dis. 2000;59(6):448–54.
doi: 10.1136/ard.59.6.448
pubmed: 10834862
pmcid: 1753153
Cecil DL, Appleton CTG, Polewski MD, Mort JS, Schmidt AM, Bendele A, et al. The pattern recognition receptor CD36 is a Chondrocyte Hypertrophy Marker Associated with suppression of catabolic responses and Promotion of repair responses to inflammatory stimuli. J Immunol. 2009;182(8):5024.
doi: 10.4049/jimmunol.0803603
pubmed: 19342682
Sun K, Luo J, Guo J, Yao X, Jing X, Guo F. The PI3K/AKT/mTOR signaling pathway in osteoarthritis: a narrative review. Osteoarthritis Cartilage. 2020;28(4):400–9.
doi: 10.1016/j.joca.2020.02.027
pubmed: 32081707
Rutkovsky AC, Yeh ES, Guest ST, Findlay VJ, Muise-Helmericks RC, Armeson K et al. Eukaryotic initiation factor 4E-binding protein as an oncogene in breast cancer. BMC Cancer 2019 19:1. 2019;19(1):1–15.
Katsara O, Kolupaeva V. mTOR-mediated inactivation of 4E-BP1, an inhibitor of translation, precedes cartilage degeneration in rat osteoarthritic knees. J Orthop Research
doi: 10.1002/jor.24049
Henrotin Y, Mathy M, Sanchez C, Lambert C. Chondroitin sulfate in the treatment of Osteoarthritis: from in Vitro studies to clinical recommendations. Ther Adv Musculoskelet Dis. 2010;2(6):335.
doi: 10.1177/1759720X10383076
pubmed: 22870459
pmcid: 3383492
Bishnoi M, Jain A, Hurkat P, Jain SK. Chondroitin sulphate: a focus on osteoarthritis. Glycoconj J. 2016;33(5):693–705.
doi: 10.1007/s10719-016-9665-3
pubmed: 27194526
Katsuragi J, Sasho T, Yamaguchi S, Akagi R, Muramatsu Y, Mukoyama S, et al. Investigation of the role of interleukin 16 in chondrogenesis of mesenchymal stem cells and in osteoarthritis. Osteoarthritis Cartilage. 2013;21:S239–40.
doi: 10.1016/j.joca.2013.02.490
Piotr A, Klimiuk JJG. IL-16 as an anti-inflammatory cytokine in Rheumatoid Synovitis. J Immunol. 1999;162(7):4293–9.
doi: 10.4049/jimmunol.162.7.4293