Burin BOONSRI, Waranee PRADİT, Kumpanart SOONTORNVIPART, Terdsak YANO, Siriwadee CHOMDEJ, Siriwan ONGCHAI, Korakot NGANVONGPANIT

Prevalence of Cartilage Erosion in Canine Patellar Luxation and Gene Expression in Affected Joints

Bu çalışmanın amacı patellar luksasyonlu (PL) küçük cüsseli köpeklerde kartilaj erozyonunun prevalansını ve osteoartritis (OA)-alakalı gen ekspresyonunu belirlemektedir. Birinci araştırmada; cins, yaş, cinsiyet ve infekte eklemi içeren PL ile ilgili risk faktörlerini belirlemek amacıyla 71 köpek incelendi. İkinci araştırmada toplam 39 köpek dört gruba ayrıldı; diz ekleminde normal artikular kartilaj (G1; n=5), kartilaj erozyon olmayan PL (G2; n=11), kartilaj erozyonlu PL (G3; n=14) ve dizde OA (G4; n=9). Cerrahi operasyon sırasında PL'u düzeltmek amacıyla artiküler kartilaj ve sinoviyal zarlar alındı. Toplam 11 adet OA ile ilgili genin (AGG, COL2A1, HAS-1, HAS-2, TIMP-1, MMP-3, IL-1?, TNF-?, IFN-?, COX-1 ve COX-2; referans gen olarak GAPDH kullanıldı) ekspresyon düzeylerini belirlemek amacıyla PCR tekniği uygulandı. Birinci araştırmanın sonucunda yaş, cinsiyet ve PL derecesi kartilaj erozyonu ile ilgili risk faktörleri olarak belirlendi (P

Köpeklerde Patellar Luksasyonda Kıkırdak Erozyonunun Prevalansı ve Etkilenmiş Eklemlerdeki Gen Ekspresyonu

The objectives of this study were to assess the prevalence of cartilage erosion in small dogs with patellar luxation (PL), and related osteoarthritis (OA)-related gene expression. In Study 1, 71 dogs were examined to determine risk factors associated with PL, including breed, age, weight, sex, and affected joint. In Study 2, a total of 39 dogs were divided into four groups: normal articular cartilage in the stifle joint (G1; n=5); PL without cartilage erosion (G2; n=11); PL with cartilage erosion (G3; n=14); and OA in the stifle (G4; n=9). Articular cartilage and synovial membranes were collected during surgical operations to correct PL. Real-time PCR was used to quantify the expression levels of 11 OA-related genes, including AGG, COL2A1, HAS-1, HAS-2, TIMP-1, MMP-3, IL-1?, TNF-?, IFN-?, COX-1, and COX-2, with GAPDH used as a reference gene. From Study 1, it was found that the risk factors related with cartilage erosion lesion were age, sex, and PL grade (all variables showed P<0.05). From Study 2, it was demonstrated that PL with or without cartilage erosion expressed pro-inflammatory cytokines and enzymes; some biomolecules were up regulated (IL-1?, MMP-3, AGG, TIMP-1) but some were down regulated (COL2A1, HAS-2, COX-1, COX-2). This expression was the difference between the articular cartilage and the synovial membrane; however, the expression of genes from PL with cartilage erosion was observed to be similar to that of OA. From our results, it can be concluded that PL can develop into secondary OA due to an increase of IL-1? in cartilage and synovial membrane.

PDF

___

Nganvongpanit K, Yano T: Prevalence of and risk factors of patellar luxation in dogs in Chiang Mai, Thailand, during the years 2006-2011. Thai J Vet Med, 41, 449-54, 2011.
Soontornvipart K, Wangdee C, Kalpravidh M, Brahmasa A, Sarikaputi M, Temwichitr J, Lavrijsen IC, Theyse LF, Leegwater PA: Incidence and genetic aspects of patellar luxation in Pomeranian dogs in Thailand. Vet J, , 122-125, 2013. DOI: 10.1016/j.tvjl.2012.07.027
Alam MR, Lee JI, Kang HS, Kim IS, Park SY, Lee KC, Kim NS: Frequency and distribution of patellar luxation in dogs. 134 cases (2000 to 2005). Vet Comp Orthop Traumatol, 20, 59-64, 2007.
Lavrijsen IC, Heuven HC, Breur GJ, Leegwater PA, Meutstege FJ, Hazewinkel HA: Phenotypic and genetic trends of patellar luxation in Dutch Flat-Coated Retrievers. Anim Genet, 44, 736-741, 2013. DOI: 10.1111/ age.12077
Wangdee C, Theyse LF, Techakumphu M, Soontornvipart K, Hazewinkel HA: Evaluation of surgical treatment of medial patellar luxation in Pomeranian dogs. Vet Comp Orthop Traumatol, 26, 435-439, 2013. DOI: 3415/VCOT-12-11-0138
Linney WR, Hammer DL, Shott S: Surgical treatment of medial patellar luxation without femoral trochlear groove deepening procedures in dogs: cases (1998-2009). J Am Vet Med Assoc, 238, 1168-1172, 2011. DOI: 2460/javma.238.9.1168
Arthurs GI, Langley-Hobbs SJ: Complications associated with corrective surgery for patellar luxation in 109 dogs. Vet Surg, 35, 559-566. 2006. DOI: 1111/j.1532-950X.2006.00189.x
Cashmore RG, Havlicek M, Perkins NR, James DR, Fearnside SM, Marchevsky AM, Black AP: Major complications and risk factors associated with surgical correction of congenital medial patellar luxation in 124 dogs. Vet Comp Orthop Traumatol, 27, 263-270, 2014. DOI: 10.3415/VCOT-13-08-0100
Chomdej S, Kuensaen C, Pradit W, Nganvongpanit K: Detection of DNA markers in dogs with patellar luxation by high annealing temperature - Random amplified polymorphic DNA analysis. Kafkas Univ Vet Fak Derg, 20, 222, 2014. DOI: 10.9775/kvfd.2013.9888
Lavrijsen IC, Leegwater PA, Wangdee C, van Steenbeek FG, Schwencke M, Breur GJ, Meutstege FJ, Nijman IJ, Cuppen E, Heuven HC, Hazewinkel HA: Genome-wide survey indicates involvement of loci on canine chromosomes 7 and 31 in patellar luxation in Flat-Coated Retrievers. BMC Genet, 28, 64, 2014. DOI: 10.1186/1471-2156-15-64
Roush JK: Canine patellar luxation. Vet Clin North Am: Small Anim Pract, , 855-68, 1993. DOI: 10.1016/S0195-5616(93)50087-6
Yeadon R, Fitzpatrick N, Kowaleski MP: Tibial tuberosity trans- position-advancement for treatment of medial patellar luxation and concomitant cranial cruciate ligament disease in the dog. Surgical technique, radiographic and clinical outcomes. Vet Comp Orthop Traumatol, 24, 18-26, 2011. DOI: 10.3415/VCOT-10-01-0015
Clements DN, Carter SD, Innes JF, Ollier WE, Day PJ: Gene expression profiling of normal and ruptured canine anterior cruciate ligaments. Osteoarthr Carti, 16, 195-203, 2008. DOI: 10.1016/j.joca.2007.06.013
Intema F, Hazewinkel HA, Gouwens D, Bijlsma JW, Weinans H, Lafeber FP, Mastbergen SC: In early OA, thinning of the subchondral plate is directly related to cartilage damage: Results from a canine ACLT- meniscectomy model. Osteoarthr Carti, 18, 691-698, 2010. DOI: 10.1016/j. joca.2010.01.004
Franklin SP, Gilley RS, Palmer RH: Meniscal injury in dogs with cranial cruciate ligament rupture. Compend Contin Educ Vet, 32, E1-10, 2010.
Kunst CM, Pease AP, Nelson NC, Habing G, Ballegeer EA: Computed tomographic identification of dysplasia and progression of osteoarthritis in dog elbows previously assigned of a grades 0 and 1. Vet Radiol Ultrasound, , 511-520, 2014. DOI: 10.1111/vru.12171
Nga nvongpanit K, Itthiarbha A, Ong-Chai S, Kongtawelert P: Evaluation of serum chondroitin sulfate and hyaluronan: Biomarkers for osteoarthritis in canine hip dysplasia. J Vet Sci, 9, 317-325, 2008.
Roy RG, Wallace LJ, Johnston GR, Wickstrom SL: A retrospective evaluation of stifle osteoarthritis in dogs with bilateral medial patellar luxation and unilateral surgical repair. Vet Surg, 21, 475-469, 1992. DOI: 1111/j.1532-950X.1992.tb00084.x
Vollnberg B, Koehlitz T, Jung T, Scheffier S, Hoburg A, Khandker D, Hamm B, Wiener E, Diederichs G: Prevalence of cartilage lesions and early osteoarthritis in patients with patellar dislocation. Eur Radiol, 22, 2347-2356, DOI: 10.1007/s00330-012-2493-3
von Engelhardt LV, Raddatz M, Bouillon B, Spahn G, Dàvid A, Haage P, Lichtinger TK: How reliable is MRI in diagnosing cartilaginous lesions in patients with first and recurrent lateral patellar dislocations? BMC Musculoskelet Disord, 11, 149, 2010. DOI: 10.1186/1471-2474-11-149
Daems R, Janssens LA, Beosier YM: Grossly apparent cartilage erosion of the patellar articular surface in dogs with congenital medial patellar luxation. Vet Comp Orthop Traumatol, 22, 222-4, 2009. DOI: 10.3415/VCOT- 08-0076
Alam MR, Ji JR, Kim MS, Kim NS: Biomarkers for identifying the early phases of osteoarthritis secondary to medial patellar luxation in dogs. J Vet Sci, 12, 273-280, 2011. DOI: 10.4142/jvs.2011.12.3.273
Alam MR, Lee HB, Kim MS, Kim NS: Surgical model of osteoarthritis secondary to medial patellar luxation in dogs. Vet Med, 11, 123-130, 2011.
Vidoni B, Sommerfeld-Stur I, Eisenmenger E: Diagnostic and genetic aspects of patellar luxation in small and miniature breed dogs in Austria. EJCAP, 16, 149-58, 2006.
Putnam RW: Patellar luxation in the dog. Ontario, Canada: University of Guelph, 1968.
van der Kraan PM, van den Berg WB: Osteophytes: Relevance and biology. Osteoarthr Carti, 15, 237-244, 2007. DOI: 10.1016/j.joca. 2006.11.006
Cook JL, Kuroki K, Visco D, Pelletier JP, Schulz L, Lafeber FP: The OARSI histopathology initiative - Recommendations for histological assessments of osteoarthritis in the dog. Osteoarthr Carti, 18, S66-S79, 2010. DOI: 10.1016/j.joca.2010.04.017.
Nganvongpanit K, Pradit W, Chomdej S: Articular cartilage gene expression after coxofemoral joint luxation in the dog. Vet Med Int, , 2013. DOI: 10.1155/2013/936317
Mazzucchelli RI, Warming S, Lawrence SM, Ishii M, Abshari M, Washington AV, Feigenbaum L, Warner AC, Sims DJ, Li WQ, Hixon JA, Gray DH, Rich BE, Morrow M, Anver MR, Cherry J, Naf D, Sternberg LR, McVicar DW, Farr AG, Germain RN, Rogers K, Jenkins NA, Copeland NG, Durum SK: Visualization and identification of IL-7 producing cells in reporter mice. PLoS One, 4, e7637, 2009. DOI: 10.1371/journal.pone.0007637
Nganvongpanit K, Yano T: Survey of articular cartilage injury of stifle joints in 323 dogs presented for surgery in Chiang Mai, Thailand, during 2012. Thai J Vet Med, 42, 489-494, 2012.
Nganvongpanit K, Pothacharoen P, Chaochird P, Klunklin K, Warrit K, Settakorn J, Pattamapaspong N, Luevitoonvechkij S, Arpornchayanon O, Kongtawelert P, Pruksakorn D: Prospective evaluation of serum biomarker levels and cartilage repair by autologous chondrocyte transplantation and subchondral drilling in a canine model. Arthritis Res Ther, 11, R78, 2009. DOI: 10.1186/ar2709
Nomura E, Inoue M: Second-look arthroscopy of cartilage changes of the patellofemoral joint, especially the patella, following acute and recurrent patellar dislocation. Osteoarthr Carti, 13, 1029-1036, 2005. DOI: 1016/j.joca.2005.07.004
Li Y, Wei X, Zhou J, Wei L: The age-related changes in cartilage and osteoarthritis. Biomed Res Int, 916530, 2013. DOI: 10.1155/2013/916530
Loeser RF: Age-related changes in the musculoskeletal system and the development of osteoarthritis. Clin Geriatr Med, 26, 371-386, 2010. DOI: 1016/j.cger.2010.03.002
Tsuchida AI, Beekhuizen M, 't Hart MC, Radstake TR, Dhert WJ, Saris DB, van Osch GJ, Creemers LB: Cytokine profiles in the joint depend on pathology, but are different between synovial fluid, cartilage tissue and cultured chondrocytes. Arthritis Res Ther, 16, 441, 2014. DOI: 10.1186/ s13075-014-0441-0
Siengdee P, Nganvongpanit K, Pothacharoen P, Chomdej S, Mekchay S, Ong-Chai S: Effects of bromelain on cellular characteristics and expression of selected genes in canine in vitro chondrocyte culture. Vet Med, , 551-560, 2010.
Haapala J, Arokoski JP, Rönkkö S, Agren U, Kosma VM, Lohmander LS, Tammi M, Helminen HJ, Kiviranta I: Decline after immobilisation and recovery after remobilisation of synovial fluid IL1, TIMP, and chondroitin sulphate levels in young beagle dogs. Ann Rheum Dis, 60, 55-60, 2001. DOI: 1136/ard.60.1.55
Lee AS, Ellman MB, Yan D, Kroin JS, Cole BJ, van Wijnen AJ, Im HJ: A current review of molecular mechanisms regarding osteoarthritis and pain. Gene, 527, 440-447, 2013. DOI: 10.1016/j.gene.2013.05.069
Bastow ER, Byers S, Golub SB, Clarkin CE, Pitsillides AA, Fosang AJ: Hyaluronan synthesis and degradation in cartilage and bone. Cell Mol Life Sci, 65, 395-413, 2008. DOI: 10.4142/jvs.2011.12.3.273
Campo GM, Avenoso A, D'Ascola A, Prestipino V, Scuruchi M, Nastasi G, Calatroni A, Campo S: Inhibition of hyaluronan synthesis reduced inflammatory response in mouse synovial fibroblasts subjected to collagen- induced arthritis. Arch Biochem Biophys, 518, 42-52, 2012. DOI: 10.1016/j. abb.2011.12.005
Scanzello CR, McKeon B, Swaim BH, DiCarlo E, Asomugha EU, Kanda V, Nair A, Lee DM, Richmond JC, Katz JN, Crow MK, Goldring SR: Synovial inflammation in patients undergoing arthroscopic meniscectomy: Molecular characterization and relationship to symptoms. Arthritis Rheum, , 391-400, 2011. DOI: 10.1002/art.30137
Lambert C, Dubuc JE, Montell E, Vergés J, Munaut C, Noël A, Henrotin Y: Gene expression pattern of cells from inflamed and normal areas of osteoarthritis synovial membrane. Arthritis Rheumatol, 66, 960-968, DOI: 10.1002/art.38315