Gene expression analysis of subchondral bone, cartilage, and synovium in naturally occurring equine palmar/plantar osteochondral disease.
horse
joint
markers
osteoarthritis
transcriptomic
Journal
Journal of orthopaedic research : official publication of the Orthopaedic Research Society
ISSN: 1554-527X
Titre abrégé: J Orthop Res
Pays: United States
ID NLM: 8404726
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
revised:
23
04
2021
received:
19
10
2020
accepted:
03
05
2021
pubmed:
17
5
2021
medline:
19
4
2022
entrez:
16
5
2021
Statut:
ppublish
Résumé
Osteoarthritis (OA) is a disease of the entire joint but the relationship between pathological events in various joint tissues is poorly understood. We examined concurrent changes in bone, cartilage, and synovium in a naturally occurring equine model of joint degeneration. Joints (n = 64) were grossly assessed for palmar/plantar osteochondral disease (POD) in racehorses that required euthanasia for unrelated reasons and assigned a grade of 0 (n = 34), 1 (n = 17), 2 or 3 (n = 13) using a recognized grading scheme. Synovium, cartilage, and subchondral bone were collected for histological and gene expression analysis. Relations between POD grade, cartilage histological score, and gene expression levels were examined using one-way analysis of variance or Kruskal-Wallis test and Spearman's correlation coefficient with corrections for multiple comparisons. Cartilage histological score increased in joints with POD grade 1 (p = 0.002) and 2 or 3 (p < 0.001) compared to 0. At grade 1, expression of COL1A1, COL2A1, and MMP1 increased and BGN decreased in subchondral bone while expression of BGN and ACAN decreased in cartilage. These changes further progressed at grades 2 and 3. POD grades 2 and 3 were associated with decreased expression of osteoclast inhibitor OPG and increased markers of cartilage degeneration (MMP13, COL1A1). Expression of the vascular endothelial growth factor decreased with POD grade and negatively correlated with cartilage histological score. Synovium showed no histological or transcriptomic changes related to pathology grade. Cartilage degeneration in POD is likely to be secondary to remodeling of the subchondral bone. Limited activation of proinflammatory and catabolic genes and moderate synovial pathology suggests distinct molecular phenotype of POD compared with OA.
Substances chimiques
Vascular Endothelial Growth Factor A
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
595-603Informations de copyright
© 2021 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals LLC.
Références
Loeser RF, Goldring SR, Scanzello CR, Goldring MB. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum. 2012;64:1697-1707.
Wen C, Lu WW, Chiu KY. Importance of subchondral bone in the pathogenesis and management of osteoarthritis from bench to bed. J Orthop Transl. 2014;2:16-15.
Loeser RF, Collins JA, Diekman BO. Ageing and the pathogenesis of osteoarthritis. Nat Rev Rheumatol. 2016;12:412-420.
Wang T, He C. Pro-inflammatory cytokines: the link between obesity and osteoarthritis. Cytokine Growth Factor Rev. 2018;44:38-50.
van den Kraan PM, van den Berg WB. Chondrocyte hypertrophy and osteoarthritis: role in initiation and progression of cartilage degeneration? Osteoarthr Cartil. 2012;20:223-232.
Danalache M, Jacobi LF, Schwitalle M, Hofmann UK. Assessment of biomechanical properties of the extracellular and pericellular matrix and their interconnection throughout the course of osteoarthritis. J Biomech. 2019;97:109409.
Sandy JD, Chan DD, Trevino RL, Wimmer MA, Plaas A. Human genome-wide expression analysis reorients the study of inflammatory mediators and biomechanics in osteoarthritis. Osteoarthr Cartil. 2015;23:1939-1945.
Hügle T, Geurts J. What drives osteoarthritis? Synovial versus subchondral bone pathology. Rheumatol (Oxford). 2017;56:1461-1471.
Roemer FW, Kwoh CK, Hannon MJ, et al. What comes first? multitissue involvement leading to radiographic osteoarthritis: magnetic resonance imaging-based trajectory analysis over four years in the osteoarthritis initiative. Arthritis Rheumatol. 2015;67:2085-2096.
Rahnamay Moshtagh P, Korthagen NM, Plomp SG, Pouran B, Zadpoor A, Weinans H. Bone remodeling is an early sign of biomechanically induced pre-osteoarthritis. Osteoarthr Cartil. 2017;25:S295-S296.
Yu D, Xu J, Liu F, Wang X, Mao Y, Zhu Z. Subchondral bone changes and the impacts on joint pain and articular cartilage degeneration in osteoarthritis. Clin Exp Rheumatol. 2016;34:929-934.
Zamli Z, Robson Brown K, Tarlton JF, et al. Subchondral bone plate thickening precedes chondrocyte apoptosis and cartilage degradation in spontaneous animal models of osteoarthritis. BioMed Res Int. 2014;2014:606870. https://doi.org/10.1155/2014/606870
Zhou X, Cao H, Yuan Y, Wu W. Biochemical signals mediate the crosstalk between cartilage and bone in osteoarthritis. BioMed Res Int. 2020;2020:5720360. https://doi.org/10.1155/2020/5720360
McIlwraith CW, Frisbie DD, Kawcak CE. The horse as a model of naturally occurring osteoarthritis. Bone Joint Res. 2012;1:297-309.
Kuyinu EL, Narayanan G, Nair LS, Laurencin CT. Animal models of osteoarthritis: classification, update, and measurement of outcomes. J Orthop Surg Res. 2016;11:19. https://doi.org/10.1186/s13018-016-0346-5
Little CB, Hunter DJ. Post-traumatic osteoarthritis: from mouse models to clinical trials. Nat Rev Rheumatol. 2013;9:485-497.
Hayami T, Pickarski M, Zhuo Y, Wesolowski GA, Rodan GA, Duong LT. Characterization of articular cartilage and subchondral bone changes in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis. Bone. 2006;38:234-243.
Gilbert SJ, Bonnet CS, Stadnik P, Duance VC, Mason DJ, Blain EJ. Inflammatory and degenerative phases resulting from anterior cruciate rupture in a non-invasive murine model of post-traumatic osteoarthritis. J Orthop Res. 2018;36:2118-2127.
Wojdasiewicz P, Poniatowski ŁA, Szukiewicz D. The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis. Mediators Inflamm. 2014;2014:561459.
Kamm JL, Nixon AJ, Witte TH. Cytokine and catabolic enzyme expression in synovium, synovial fluid and articular cartilage of naturally osteoarthriticequine carpi. Equine Vet J. 2010;42:693-699.
Norrdin RW, Kawcak CE, Capwell BA, McIlwraith CW. Subchondral bone failure in an equine model of overload arthrosis. Bone. 1998;22:133-139.
Stewart HL, Kawcak CE. The importance of subchondral bone in the pathophysiology of osteoarthritis. Front Vet Sci. 2018;5:178.
Davis AM, Fan X, Shen L, Robinson P, Riggs CM. Improved radiological diagnosis of palmar osteochondral disease in the Thoroughbred racehorse. Equine Vet J. 2017;48:228-233.
Pinchbeck GL, Clegg PD, Boyde A, Riggs CM. Pathological and clinical features associated with palmar/plantar osteochondral disease of the metacarpo/metatarsophalangeal joint in Thoroughbred racehorses. Equine Vet J. 2013;45:587-592.
Pinilla MJ, Tranquille CA, Blunden AS, Chang YM, Parkin T, Murray RC. Histological features of the distal third metacarpal bone in thoroughbred racehorses, with and without lateral condylar fractures. J Comp Pathol. 2017;157:1-10.
Barr ED, Pinchbeck GL, Clegg PD, Boyde A, Riggs CM. Post mortem evaluation of palmar osteochondral disease (traumatic osteochondrosis) of the metacarpo/metatarsophalangeal joint in Thoroughbred racehorses. Equine Vet J. 2009;41:366-371.
Little CB, Smith MM, Cake MA, Read RA, Murphy MJ, Barry FP. The OARSI histopathology initiative-recommendations for histological assessments of osteoarthritis in sheep and goats. Osteoarthr Cartil. 2010;18(suppl 3):S80-S92.
Krenn V, Morawietz L, Burmester GR, et al. Synovitis score: discrimination between chronic low-grade and high-grade synovitis. Histopathology. 2006;49:358-364.
Chomczynski P, Sacchi N. The single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction: twenty-something years on. Nat Protoc. 2006;1:581-585.
Turley SM, Thambyah A, Riggs CM, Firth EC, Broom ND. Microstructural changes in cartilage and bone related to repetitive overloading in an equine athlete model. J Anat. 2014;224:647-658.
Lahm A, Mrosek E, Spank H, et al. Changes in content and synthesis of collagen types and proteoglycans in osteoarthritis of the knee joint and comparison of quantitative analysis with Photoshop-based image analysis. Arch Orthop Trauma Surg. 2010;130:557-564.
Tanaka N, Tashiro T, Katsuragawa Y, Sawabe M, Furukawa H, Fukui N. Expression of minor cartilage collagens and small leucine rich proteoglycans may be relatively reduced in osteoarthritic cartilage. BMC Musculoskelet Disord. 2019;20:232. https://doi.org/10.1186/s12891-019-2596-y
Rai MF, Sandell LJ, Zhang B, Wright RW, Brophy RH. RNA microarray analysis of macroscopically normal articular cartilage from knees undergoing partial medial meniscectomy: potential prediction of the risk for developing osteoarthritis. PLOS One. 2016;11:0155373. https://doi.org/10.1371/journal.pone.0155373
Sieker JT, Proffen BL, Waller KA, et al. Transcriptional profiling of articular cartilage in a porcine model of early post-traumatic osteoarthritis. J Orthop Res. 2018;36:318-329.
Brew CJ, Clegg PD, Boot-Handford RP, Andrew JG, Hardingham T. Gene expression in human chondrocytes in late osteoarthritis is changed in both fibrillated and intact cartilage without evidence of generalised chondrocyte hypertrophy. Ann Rheum Dis. 2010;69:234-240.
Montaseri A, Busch F, Mobasheri A, et al. IGF-1 and PDGF-bb suppress IL-1β-induced cartilage degradation through down-regulation of NF-κB signaling: involvement of Src/PI-3k/AKT pathway. PLOS One. 2011;6:28663. https://doi.org/10.1371/journal.pone.0028663
Salazar-Noratto GE, de Nijs N, Stevens HY, Gibson G, Guldberg RE. Regional gene expression analysis of multiple tissues in an experimental animal model of post-traumatic osteoarthritis. Osteoarthr Cartil. 2019;27:294-303.
Chang JC, Sebastian A, Murugesh DK, et al. Global molecular changes in a tibial compression induced ACL rupture model of post-traumatic osteoarthritis. J Orthop Res. 2017;35:474-485.
Sebastian A, Chang JC, Mendez ME, et al. Comparative transcriptomics identifies novel genes and pathways involved in post-traumatic osteoarthritis development and progression. Int J Mol Sci. 2018;19:2657.
Kevorkian L, Young DA, Darrah C, et al. Expression profiling of metalloproteinases and their inhibitors in cartilage. Arthritis Rheum. 2004;50:131-141.
Smith KJ, Bertone AL, Weisbrode SE, Radmacher M. Gross, histologic, and gene expression characteristics of osteoarthritic articular cartilage of the metacarpal condyle of horses. Am J Vet Res. 2006;67:1299-1306.
Li H, Wang D, Yuan Y, Min J. New insights on the MMP-13 regulatory network in the pathogenesis of early osteoarthritis. Arthritis Res Ther. 2017;19:248.
Goldring MB, Otero M, Plumb DA, et al. Roles of inflammatory and anabolic cytokines in cartilage metabolism: signals and multiple effectors converge upon MMP-13 regulation in osteoarthritis. Eur. Cells Mater. 2011;21:202-220.
Chou CH, Wu CC, Song IW, et al. Genome-wide expression profiles of subchondral bone in osteoarthritis. Arthritis Res Ther. 2013;15:R190.
Gu HY, Yang M, Guo J, et al. Identification of the biomarkers and pathological process of osteoarthritis: weighted gene co-expression network analysis. Front Physiol. 2019;10:275. https://doi.org/10.3389/fphys.2019.00275
Zhang R, Fang H, Chen Y, et al. Gene expression analyses of subchondral bone in early experimental osteoarthritis by microarray. PLOS One. 2012;7:32356. https://doi.org/10.1371/journal.pone.0032356
Corsi A, Xu T, Chen XD, et al. Phenotypic effects of biglycan deficiency are linked to collagen fibril abnormalities, are synergized by decorin deficiency, and mimic Ehlers-Danlos-like changes in bone and other connective tissues. J Bone Miner Res. 2002;17:1180-1189.
Nagao M, Hamilton JL, Kc R, et al. Vascular endothelial growth factor in cartilage development and osteoarthritis. Sci Rep. 2017;7:13027.
Liu Y, Berendsen AD, Jia S, et al. Intracellular VEGF regulates the balance between osteoblast and adipocyte differentiation. J Clin Invest. 2012;122:3101-3113.
Zupan J, Vrtačnik P, Cör A, et al. VEGF-A is associated with early degenerative changes in cartilage and subchondral bone. Growth Factors. 2018;36:263-273.