BMC Musculoskeletal Disorders | |
Synoviocytes protect cartilage from the effects of injury in vitro | |
David D Frisbie1  Alan J Grodzinsky2  C Wayne McIlwraith1  John D Kisiday1  Christina M Lee1  | |
[1] Orthopaedic Research Center, Department of Clinical Sciences, College of Veterinary Medicine, Colorado State University, 300 West Drake Rd., Fort Collins, Colorado CO 80523, USA;Biomedical Engineering, Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave, Cambridge, MA, 02139, USA | |
关键词: Injury; Synovial cell; Cartilage; | |
Others : 1134045 DOI : 10.1186/1471-2474-14-54 |
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received in 2012-04-16, accepted in 2013-01-22, 发布年份 2013 | |
【 摘 要 】
Background
It is well documented that osteoarthritis (OA) can develop following traumatic joint injury and is the leading cause of lameness and subsequent wastage of equine athletes. Although much research of injury induced OA has focused on cartilage, OA is a disease that affects the whole joint organ.
Methods
In this study, we investigated the impact of synovial cells on the progression of an OA phenotype in injured articular cartilage. Injured and control cartilage were cultured in the presence of synoviocytes extracted from normal equine synovium. Synoviocytes and cartilage were evaluated for catabolic and anabolic gene expression. The cartilage was also evaluated histologically for loss of extracellular matrix molecules, chondrocyte cell death and chondrocyte cluster formation.
Results
The results indicate synoviocytes exert both positive and negative effects on injured cartilage, but ultimately protect injured cartilage from progressing toward an OA phenotype. Synoviocytes cultured in the presence of injured cartilage had significantly reduced expression of aggrecanase 1 and 2 (ADAMTS4 and 5), but also had increased expression of matrix metalloproteinase (MMP) -1 and reduced expression of tissue inhibitor of metalloproteinases 1 (TIMP-1). Injured cartilage cultured with synoviocytes had increased expression of both collagen type 2 and aggrecanase 2. Histologic examination of cartilage indicated that there was a protective effect of synoviocytes on injured cartilage by reducing the incidence of both focal cell loss and chondrocyte cluster formation, two major hallmarks of OA.
Conclusions
These results support the importance of evaluating more than one synovial joint tissue when investigating injury induced OA.
【 授权许可】
2013 Lee et al; licensee BioMed Central Ltd.
【 预 览 】
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【 参考文献 】
- [1]Auer JA, Stick JA: Equine surgery. 2nd edition. Philadelphia: W.B. Saunders; 1999.
- [2]Loeuille D, Chary-Valckenaere I, Champigneulle J, Rat AC, Toussaint F, Pinzano-Watrin A, Goebel JC, Mainard D, Blum A, Pourel J: Macroscopic and microscopic features of synovial membrane inflammation in the osteoarthritic knee: correlating magnetic resonance imaging findings with disease severity. Arthritis Rheum 2005, 52(11):3492-3501.
- [3]Ostergaard M, Stoltenberg M, Lovgreen-Nielsen P, Volck B, Jensen CH, Lorenzen I: Magnetic resonance imaging-determined synovial membrane and joint effusion volumes in rheumatoid arthritis and osteoarthritis: comparison with the macroscopic and microscopic appearance of the synovium. Arthritis Rheum 1997, 40(10):1856-1867.
- [4]Fernandez-Madrid F, Karvonen RL, Teitge RA, Miller PR, An T, Negendank WG: Synovial thickening detected by MR imaging in osteoarthritis of the knee confirmed by biopsy as synovitis. Magn Reson Imaging 1995, 13(2):177-183.
- [5]Benito MJ, Veale DJ, FitzGerald O, van den Berg WB, Bresnihan B: Synovial tissue inflammation in early and late osteoarthritis. Ann Rheum Dis 2005, 64(9):1263-1267.
- [6]McIlwraith CW, Van Sickle DC: Experimentally induced arthritis of the equine carpus: histologic and histochemical changes in the articular cartilage. Am J Vet Res 1981, 42(2):209-217.
- [7]Bertone AL, Palmer JL, Jones J: Synovial fluid cytokines and eicosanoids as markers of joint disease in horses. Vet Surg 2001, 30(6):528-538.
- [8]Irie K, Uchiyama E, Iwaso H: Intraarticular inflammatory cytokines in acute anterior cruciate ligament injured knee. Knee 2003, 10(1):93-96.
- [9]Lohmander LS, Hoerrner LA, Lark MW: Metalloproteinases, tissue inhibitor, and proteoglycan fragments in knee synovial fluid in human osteoarthritis. Arthritis Rheum 1993, 36(2):181-189.
- [10]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(10):1196-1204.
- [11]Kamm JL, Nixon AJ, Witte TH: Cytokine and catabolic enzyme expression in synovium, synovial fluid and articular cartilage of naturally osteoarthritic equine carpi. Equine Vet J 2010, 42(8):693-699.
- [12]Borden P, Solymar D, Sucharczuk A, Lindman B, Cannon P, Heller RA: Cytokine control of interstitial collagenase and collagenase-3 gene expression in human chondrocytes. J Biol Chem 1996, 271(38):23577-23581.
- [13]Patwari P, Cook MN, DiMicco MA, Blake SM, James IE, Kumar S, Cole AA, Lark MW, Grodzinsky AJ: Proteoglycan degradation after injurious compression of bovine and human articular cartilage in vitro: interaction with exogenous cytokines. Arthritis Rheum 2003, 48(5):1292-1301.
- [14]Loeser RF: Molecular mechanisms of cartilage destruction: mechanics, inflammatory mediators, and aging collide. Arthritis Rheum 2006, 54(5):1357-1360.
- [15]Goldring MB, Goldring SR: Osteoarthritis. J Cell Physiol 2007, 213(3):626-634.
- [16]D’Andrea P, Calabrese A, Grandolfo M: Intercellular calcium signalling between chondrocytes and synovial cells in co-culture. Biochem J 1998, 329(Pt 3):681-687.
- [17]Dingle JT, Saklatvala J, Hembry R, Tyler J, Fell HB, Jubb R: A cartilage catabolic factor from synovium. Biochem J 1979, 184(1):177-180.
- [18]Gregg AJ, Fortier LA, Mohammed HO, Mayr KG, Miller BJ, Haupt JL: Assessment of the catabolic effects of interleukin-1beta on proteoglycan metabolism in equine cartilage cocultured with synoviocytes. Am J Vet Res 2006, 67(6):957-962.
- [19]Patwari P, Lin SN, Kurz B, Cole AA, Kumar S, Grodzinsky AJ: Potent inhibition of cartilage biosynthesis by coincubation with joint capsule through an IL-1-independent pathway. Scand J Med Sci Sports 2009, 19(4):528-535.
- [20]Lee JH, Fitzgerald JB, DiMicco MA, Cheng DM, Flannery CR, Sandy JD, Plaas AH, Grodzinsky AJ: Co-culture of mechanically injured cartilage with joint capsule tissue alters chondrocyte expression patterns and increases ADAMTS5 production. Arch Biochem Biophys 2009, 489(1–2):118-126.
- [21]Rosengren S, Boyle DL, Firestein GS: Acquisition, culture, and phenotyping of synovial fibroblasts. Methods Mol Med 2007, 135:365-375.
- [22]Cagnard N, Letourneur F, Essabbani A, Devauchelle V, Mistou S, Rapinat A, Decraene C, Fournier C, Chiocchia G: Interleukin-32, CCL2, PF4F1 and GFD10 are the only cytokine/chemokine genes differentially expressed by in vitro cultured rheumatoid and osteoarthritis fibroblast-like synoviocytes. Eur Cytokine Netw 2005, 16(4):289-292.
- [23]Lee CM, Kisiday JD, McIlwraith CW, Grodzinsky AJ, Frisbie D: Development of an in vitro model of injury induced osteoarthritis in adult equine cartilage using single impact compressive overload. Am J Vet Res 2013, 74(1):40-47.
- [24]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(4):402-408.
- [25]McIlwraith CW, Frisbie DD, Kawcak CE, Fuller CJ, Hurtig M, Cruz A: The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the horse. Osteoarthr Cartil 2010, 18(3):93-105.
- [26]Jones GC, Riley GP: ADAMTS proteinases: a multi-domain, multi-functional family with roles in extracellular matrix turnover and arthritis. Arthritis Res Ther 2005, 7(4):160-169. BioMed Central Full Text
- [27]Lark MW, Gordy JT, Weidner JR, Ayala J, Kimura JH, Williams HR, Mumford RA, Flannery CR, Carlson SS, Iwata M: Cell-mediated catabolism of aggrecan. Evidence that cleavage at the “aggrecanase” site (Glu373-Ala374) is a primary event in proteolysis of the interglobular domain. J Biol Chem 1995, 270(6):2550-2556.
- [28]Clutterbuck AL, Harris P, Allaway D, Mobasheri A: Matrix metalloproteinases in inflammatory pathologies of the horse. Vet J 2010, 183(1):27-38.
- [29]Roos H, Dahlberg L, Hoerrner LA, Lark MW, Thonar EJ, Shinmei M, Lindqvist U, Lohmander LS: Markers of cartilage matrix metabolism in human joint fluid and serum: the effect of exercise. Osteoarthr Cartil 1995, 3(1):7-14.
- [30]Lohmander LS, Hoerrner LA, Dahlberg L, Roos H, Bjornsson S, Lark MW: Stromelysin, tissue inhibitor of metalloproteinases and proteoglycan fragments in human knee joint fluid after injury. J Rheumatol 1993, 20(8):1362-1368.
- [31]Lohmander LS, Roos H, Dahlberg L, Hoerrner LA, Lark MW: Temporal patterns of stromelysin-1, tissue inhibitor, and proteoglycan fragments in human knee joint fluid after injury to the cruciate ligament or meniscus. J Orthop Res 1994, 12(1):21-28.
- [32]Yoshihara Y, Nakamura H, Obata K, Yamada H, Hayakawa T, Fujikawa K, Okada Y: Matrix metalloproteinases and tissue inhibitors of metalloproteinases in synovial fluids from patients with rheumatoid arthritis or osteoarthritis. Ann Rheum Dis 2000, 59(6):455-461.
- [33]Martel-Pelletier J, McCollum R, Fujimoto N, Obata K, Cloutier JM, Pelletier JP: Excess of metalloproteases over tissue inhibitor of metalloprotease may contribute to cartilage degradation in osteoarthritis and rheumatoid arthritis. Lab Invest 1994, 70(6):807-815.
- [34]Konttinen YT, Ainola M, Valleala H, Ma J, Ida H, Mandelin J, Kinne RW, Santavirta S, Sorsa T, Lopez-Otin C: Analysis of 16 different matrix metalloproteinases (MMP-1 to MMP-20) in the synovial membrane: different profiles in trauma and rheumatoid arthritis. Ann Rheum Dis 1999, 58(11):691-697.
- [35]van den Boom R, van der Harst MR, Brommer H, Brama PA, Barneveld A, van Weeren PR, DeGroot J: Relationship between synovial fluid levels of glycosaminoglycans, hydroxyproline and general MMP activity and the presence and severity of articular cartilage change on the proximal articular surface of P1. Equine Vet J 2005, 37(1):19-25.
- [36]Durigova M, Nagase H, Mort JS, Roughley PJ: MMPs are less efficient than ADAMTS5 in cleaving aggrecan core protein. Matrix Biol 2011, 30(2):145-153.
- [37]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(6):R187. BioMed Central Full Text
- [38]Ross TN, Kisiday JD, Hess T, McIlwraith CW: Evaluation of the inflammatory response in experimentally induced synovitis in the horse: a comparison of recombinant equine interleukin 1 beta and lipopolysaccharide. Osteoarthr Cartil 2012, 20(12):1583-1590.
- [39]Goldberg A: Effects of growth factors on articular cartilage. Ortop Traumatol Rehabil 2001, 3(2):209-212.
- [40]Cheng J, Wang Y, Wang Z, Yang M, Wu Y: Differential regulation of proteoglycan-4 expression by IL-1alpha and TGF-beta1 in rat condylar chondrocytes. Tohoku J Exp Med 2010, 222(3):211-218.
- [41]Stevens MM, Marini RP, Martin I, Langer R, Prasad Shastri V: FGF-2 enhances TGF-beta1-induced periosteal chondrogenesis. J Orthop Res 2004, 22(5):1114-1119.
- [42]Mienaltowski MJ, Huang L, Frisbie DD, McIlwraith CW, Stromberg AJ, Bathke AC, Macleod JN: Transcriptional profiling differences for articular cartilage and repair tissue in equine joint surface lesions. BMC Med Genomics 2009, 2:60. BioMed Central Full Text
- [43]Glasson SS, Askew R, Sheppard B, Carito B, Blanchet T, Ma HL, Flannery CR, Peluso D, Kanki K, Yang Z: Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis. Nature 2005, 434(7033):644-648.
- [44]Jeffrey JE, Gregory DW, Aspden RM: Matrix damage and chondrocyte viability following a single impact load on articular cartilage. Arch Biochem Biophys 1995, 322(1):87-96.
- [45]Jeffrey JE, Thomson LA, Aspden RM: Matrix loss and synthesis following a single impact load on articular cartilage in vitro. Biochim Biophys Acta 1997, 1334(2–3):223-232.
- [46]Stanton H, Rogerson FM, East CJ, Golub SB, Lawlor KE, Meeker CT, Little CB, Last K, Farmer PJ, Campbell IK: ADAMTS5 is the major aggrecanase in mouse cartilage in vivo and in vitro. Nature 2005, 434(7033):648-652.
- [47]Simon WH, Richardson S, Herman W, Parsons JR, Lane J: Long-term effects of chondrocyte death on rabbit articular cartilage in vivo. J Bone Joint Surg Am 1976, 58(4):517-526.
- [48]Perez HE, Luna MJ, Rojas ML, Kouri JB: Chondroptosis: an immunohistochemical study of apoptosis and Golgi complex in chondrocytes from human osteoarthritic cartilage. Apoptosis 2005, 10(5):1105-1110.
- [49]Sharif M, Whitehouse A, Sharman P, Perry M, Adams M: Increased apoptosis in human osteoarthritic cartilage corresponds to reduced cell density and expression of caspase-3. Arthritis Rheum 2004, 50(2):507-515.
- [50]Aigner T, Kim HA: Apoptosis and cellular vitality: issues in osteoarthritic cartilage degeneration. Arthritis Rheum 2002, 46(8):1986-1996.
- [51]Chen CT, Burton-Wurster N, Borden C, Hueffer K, Bloom SE, Lust G: Chondrocyte necrosis and apoptosis in impact damaged articular cartilage. J Orthop Res 2001, 19(4):703-711.
- [52]Mankin HJ, Dorfman H, Lippiello L, Zarins A: Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. II. Correlation of morphology with biochemical and metabolic data. J Bone Joint Surg Am 1971, 53(3):523-537.
- [53]Poole CA: Articular cartilage chondrons: form, function and failure. J Anat 1997, 191(Pt 1):1-13.
- [54]von der Mark K, Kirsch T, Nerlich A, Kuss A, Weseloh G, Gluckert K, Stoss H: Type X collagen synthesis in human osteoarthritic cartilage. Indication of chondrocyte hypertrophy. Arthritis Rheum 1992, 35(7):806-811.
- [55]Rees JA, Ali SY: Ultrastructural localisation of alkaline phosphatase activity in osteoarthritic human articular cartilage. Ann Rheum Dis 1988, 47(9):747-753.
- [56]Pullig O, Weseloh G, Ronneberger D, Kakonen S, Swoboda B: Chondrocyte differentiation in human osteoarthritis: expression of osteocalcin in normal and osteoarthritic cartilage and bone. Calcif Tissue Int 2000, 67(3):230-240.
- [57]Rees JA, Ali SY, Brown RA: Ultrastructural localisation of fibronectin in human osteoarthritic articular cartilage. Ann Rheum Dis 1987, 46(11):816-822.
- [58]da Silva MA, Yamada N, Clarke NM, Roach HI: Cellular and epigenetic features of a young healthy and a young osteoarthritic cartilage compared with aged control and OA cartilage. J Orthop Res 2009, 27(5):593-601.
- [59]Koga H, Muneta T, Ju YJ, Nagase T, Nimura A, Mochizuki T, Ichinose S, von der Mark K, Sekiya I: Synovial stem cells are regionally specified according to local microenvironments after implantation for cartilage regeneration. Stem Cells 2007, 25(3):689-696.
- [60]Djouad F, Bony C, Haupl T, Uze G, Lahlou N, Louis-Plence P, Apparailly F, Canovas F, Reme T, Sany J: Transcriptional profiles discriminate bone marrow-derived and synovium-derived mesenchymal stem cells. Arthritis Res Ther 2005, 7(6):R1304-R1315. BioMed Central Full Text