FOXO1, PXK, PYCARD and SAMD9L are differentially expressed by fibroblast-like cells in equine synovial membrane compared to joint capsule.
Abstract: The synovial membrane lines the luminal side of the joint capsule in synovial joints. It maintains joint homeostasis and plays a crucial role in equine joint pathology. When trauma or inflammation is induced in a joint, the synovial membrane influences progression of joint damage. Equine synovial membrane research is hampered by a lack of markers of fibroblast-like synoviocytes (FLS) to distinguish FLS from other fibroblast-like cells in musculoskeletal connective tissues. The aim of this study is to identify potential FLS markers of the equine synovial membrane using microarray to compare between gene expression in equine synovial membrane and the joint capsule in metacarpophalangeal joints. Results: Microarray analysis of tissues from 6 horses resulted in 1167 up-regulated genes in synovial membrane compared with joint capsule. Pathway analysis resulted in 241 candidate genes. Of these, 15 genes were selected for further confirmation as genes potentially expressed by fibroblast-like synoviocytes. Four genes: FOXO1, PXK, PYCARD and SAMD9L were confirmed in 9 horses by qPCR as differentially expressed in synovial membrane compared to joint capsule. Conclusions: In conclusion, FOXO1, PXK, PYCARD and SAMD9L were confirmed as differentially expressed in synovial membrane compared to joint capsule. These four genes are potential markers of fibroblast-like synoviocytes of the synovial membrane. As these genes are overexpressed in synovial membrane compared to joint capsule, these genes could shed light on synovial membrane physiology and its role in joint disease.
Publication Date: 2017-04-14 PubMed ID: 28410619PubMed Central: PMC5391632DOI: 10.1186/s12917-017-1003-xGoogle Scholar: Lookup
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.
- Comparative Study
- Journal Article
Summary
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 research article explores an equine’s joint health by focusing on the way certain genes are expressed differently in the synovial membrane and in the joint capsule. The studied genes could potentially serve as markers for fibroblast-like synoviocytes, helping further research into the physiology of the synovial membrane and its role in joint diseases.
Purpose of the Study
- The research was conducted to identify potential markers of fibroblast-like synoviocytes (FLS) in the synovial membrane of equines.
- A better understanding of these markers could help distinguish FLS from other fibroblast-like cells, paving the way for more comprehensive research on joint health in horses.
Methods Employed
- Gene expression in the synovial membrane and the joint capsule of the metacarpophalangeal joints were compared using a technique known as microarray.
- The study utilized tissues from 6 horses during the microarray analysis. An additional 9 horses were then used to confirm the differential gene expression found in the microarray analysis by means of qPCR.
Results of the Research
- The microarray analysis identified 1167 genes which were up-regulated in the synovial membrane compared with the joint capsule.
- Out of these, pathway analysis singled out 241 candidate genes.
- Further testing from this pool of candidate genes highlighted 15 genes for possible expression by fibroblast-like synoviocytes.
- More specifically, four genes – FOXO1, PXK, PYCARD, and SAMD9L – were confirmed to be differentially expressed in the synovial membrane when compared to the joint capsule.
Conclusions and Implications
- FOXO1, PXK, PYCARD, and SAMD9L were successfully identified as differentially expressed in the synovial membrane and are potential markers for fibroblast-like synoviocytes.
- As these genes are over-expressed in the synovial membrane, it implies these genes might be key players in the function and physiology of the synovial membrane and potentially in equine joint diseases.
- The understanding and identification of these genes could lead to improved diagnostic and therapeutic options for equine joint diseases in the future.
Cite This Article
APA
Thomsen LN, Thomsen PD, Downing A, Talbot R, Berg LC.
(2017).
FOXO1, PXK, PYCARD and SAMD9L are differentially expressed by fibroblast-like cells in equine synovial membrane compared to joint capsule.
BMC Vet Res, 13(1), 106.
https://doi.org/10.1186/s12917-017-1003-x Publication
Researcher Affiliations
- Department of Veterinary Clinical Sciences, University of Copenhagen, Hoejbakkegaards alle 5, 2630, Taastrup, Denmark.
- Department of Veterinary and Animal Sciences, University of Copenhagen, Groennegaardsvej 7, 1870, Frederiksberg C, Denmark.
- Edinburgh Genomics, Ashworth Laboratories, University of Edinburgh, Edinburgh, EH9 3FL, UK.
- Edinburgh Genomics, Ashworth Laboratories, University of Edinburgh, Edinburgh, EH9 3FL, UK.
- Department of Veterinary Clinical Sciences, University of Copenhagen, Hoejbakkegaards alle 5, 2630, Taastrup, Denmark. lcb@sund.ku.dk.
MeSH Terms
- Animals
- Biomarkers / metabolism
- Fibroblasts / metabolism
- Gene Expression Regulation
- Horses / metabolism
- Joint Capsule / cytology
- Joint Capsule / metabolism
- Real-Time Polymerase Chain Reaction
- Synovial Membrane / cytology
- Synovial Membrane / metabolism
- Synoviocytes / metabolism
- Tissue Array Analysis
- Up-Regulation
References
This article includes 38 references
- Goodrich LR, Nixon AJ. Medical treatment of osteoarthritis in the horse - a review.. Vet J 2006;171:51–69.
- Bondeson J, Wainwright SD, Lauder S, Amos N, Hughes CE. The role of synovial macrophages and macrophage-produced cytokines in driving aggrecanases, matrix metalloproteinases, and other destructive and inflammatory responses in osteoarthritis.. Arthritis Res Ther 2006;8:R187.
- Chang SK, Gu Z, Brenner MB. Fibroblast-like synoviocytes in inflammatory arthritis pathology: the emerging role of cadherin-11.. Immunol Rev 2010;233:256–266.
- Levick JR, McDonald JN. Fluid movement across synovium in healthy joints: role of synovial fluid macromolecules.. Ann Rheum Dis 1995;54:417–423.
- Graabaek PM. Ultrastructural Evidence for 2 Distinct Types of Synoviocytes in Rat Synovial-Membrane.. J Ultrastruct Res 1982;78:321–339.
- Iwanaga T, Shikichi M, Kitamura H, Yanase H, Nozawa-Inoue K. Morphology and functional roles of synoviocytes in the joint.. Arch Histol Cytol 2000;63:17–31.
- Key J. The mechanisms involved in the removal of colloidal and particulate carbon from joint cavities.. J Bone Joint Surg 1926;8:666–683.
- Graabaek PM. Characteristics of the 2 Types of Synoviocytes in Rat Synovial-Membrane - An Ultrastructural-Study.. Lab Investig 1984;50:690–702.
- Athanasou NA, Quinn J. Immunocytochemical analysis of human synovial lining cells: phenotypic relation to other marrow derived cells.. Ann Rheum Dis 1991;50:311–315.
- Bartok B, Firestein GS. Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis.. Immunol Rev 2010;233:233–255.
- Kunisch E, Fuhrmann R, Roth A, Winter R, Lungershausen W, Kinne RW. Macrophage specificity of three anti-CD68 monoclonal antibodies (KP1, EBM11, and PGM1) widely used for immunohistochemistry and flow cytometry.. Ann Rheum Dis 2004;63:774–784.
- Muller-Ladner U, Ospelt C, Gay S, Distler O, Pap T. Cells of the synovium in rheumatoid arthritis. Synovial fibroblasts.. Arthritis Res Ther 2007;9:223.
- Kiener HP, Watts GF, Cui Y, Wright J, Thornhill TS, Skold M. Synovial fibroblasts self-direct multicellular lining architecture and synthetic function in three-dimensional organ culture.. Arthritis Rheum 2010;62:742–752.
- Clarkin CE, Allen S, Kuiper NJ, Wheeler BT, Wheeler-Jones CP, Pitsillides AA. Regulation of UDP-glucose dehydrogenase is sufficient to modulate hyaluronan production and release, control sulfated GAG synthesis, and promote chondrogenesis.. J Cell Physiol 2011;226:749–761.
- Edwards JC. The nature and origins of synovium: experimental approaches to the study of synoviocyte differentiation.. J Anat 1994;184(Pt 3):493–501.
- Wilkinson LS, Pitsillides AA, Worrall JG, Edwards JC. Light microscopic characterization of the fibroblast-like synovial intimal cell (synoviocyte). Arthritis Rheum 1992;35:1179–1184.
- Valencia X, Higgins JM, Kiener HP, Lee DM, Podrebarac TA, Dascher CC. Cadherin-11 provides specific cellular adhesion between fibroblast-like synoviocytes.. J Exp Med 2004;200:1673–1679.
- Agbase.2012. http://www.agbase.msstate.edu. Accessed 29 June 2012.
- McCarthy F, Gresham C, Buza T, Chouvarine P, Pillai L, Kumar R. AgBase: supporting functional modeling in agricultural organisms.. Nucleic Acids Res 2011;39:D497–D506.
- Ingenuity Pathway Analysis (IPA).29–6-2012. www.ingenuity.com/products/ipa. Accessed 3 July 2012.
- Ensembl. 2012. http://Oct2012.archive.ensembl.org.1-10-2012. Accessed 1 Oct 2012.
- Rozen S, Skaletsky H. Primer3 on the WWW for general users and for biologist programmers.. Methods Mol Biol 2000;132:365–386.
- NCBI BLAST .2012. http://blast.ncbi.nlm.nih.gov/Blast.cgi. Accessed 1 Oct 2012.
- Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method.. Methods 2001;25:402–408.
- Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR.. Nucleic Acids Res 2001;29:e45.
- Barrey E, Mucher E, Jeansoule N, Larcher T, Guigand L, Herszberg B. Gene expression profiling in equine polysaccharide storage myopathy revealed inflammation, glycogenesis inhibition, hypoxia and mitochondrial dysfunctions.. BMC Vet Res 2009;5:29.
- Huang L, Zhu W, Saunders CP, MacLeod JN, Zhou M, Stromberg AJ. A novel application of quantile regression for identification of biomarkers exemplified by equine cartilage microarray data.. BMC Bioinformatics 2008;9:300.
- Rinn JL, Bondre C, Gladstone HB, Brown PO, Chang HY. Anatomic demarcation by positional variation in fibroblast gene expression programs.. PLoS Genet 2006;2:e119.
- Frisbie DD, Al-Sobayil F, Billinghurst RC, Kawcak CE, McIlwraith CW. Changes in synovial fluid and serum biomarkers with exercise and early osteoarthritis in horses.. Osteoarthr Cartil 2008;16:1196–1204.
- Brommer H, van Weeren PR, Brama PA, Barneveld A. Quantification and age-related distribution of articular cartilage degeneration in the equine fetlock joint.. Equine Vet J 2003;35:697–701.
- Todhunter RJ, Fubini SL, Freeman KP, Lust G. Concentrations of keratan sulfate in plasma and synovial fluid from clinically normal horses and horses with joint disease.. J Am Vet Med Assoc 1–2-1997;210:369-374.
- Kode A, Mosialou I, Silva BC, Josha S, Ferron M, Rached MT. FoxO1 protein cooperates with ATF4 protein in osteoblasts to control glucose homeostasis.. J Biol Chem 2012;287:8757–8766.
- Chung S, Lee TJ, Reader BF, Kim JY, Lee YG, Park GY. FoxO1 regulates allergic asthmatic inflammation through regulating polarization of the macrophage inflammatory phenotype.. Oncotarget 2016;7(14):17532–46.
- Ludikhuize J, de LD GD, Smeets TJ, Vinkenoog M, Sanders ME. Inhibition of forkhead box class O family member transcription factors in rheumatoid synovial tissue.. Arthritis Rheum 2007;56:2180–2191.
- Takeuchi H, Takeuchi T, Gao J, Cantley LC, Hirata M. Characterization of PXK as a protein involved in epidermal growth factor receptor trafficking.. Mol Cell Biol 2010;30:1689–1702.
- Taniguchi S, Sagara J. Regulatory molecules involved in inflammasome formation with special reference to a key mediator protein, ASC.. Semin Immunopathol 2007;29:231–238.
- Rosengren S, Hoffman HM, Bugbee W, Boyle DL. Expression and regulation of cryopyrin and related proteins in rheumatoid arthritis synovium.. Ann Rheum Dis 2005;64:708–714.
- Gallant-Behm CL, Ramsey MR, Bensard DL, Nojek I, Tran J, Liu M. Delta Np63 alpha represses anti-proliferative genes via H2A.Z deposition.. Genes Dev 2012;26:2325–2336.
Citations
This article has been cited 2 times.- Gao J, Liu H, Li L, Guo C, Wang Z, Cheng M, Tan S, Chen L, Shi J, Wu H, Feng C, Yu G, Ding C. Comprehensive proteomic characterization of urethral stricture disease in the Chinese population. Front Mol Biosci 2024;11:1401970.
- Zamith Cunha R, Zannoni A, Salamanca G, De Silva M, Rinnovati R, Gramenzi A, Forni M, Chiocchetti R. Expression of cannabinoid (CB1 and CB2) and cannabinoid-related receptors (TRPV1, GPR55, and PPARα) in the synovial membrane of the horse metacarpophalangeal joint. Front Vet Sci 2023;10:1045030.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists