{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:49:28Z","timestamp":1782283768655,"version":"3.54.5"},"reference-count":56,"publisher":"American Veterinary Medical Association (AVMA)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:p><jats:bold>OBJECTIVE<\/jats:bold> To determine effects of transforming growth factor (TGF)-\u03b2 and interleukin (IL)-1\u03b2 on inflammatory markers in cultured canine chondrocytes to clarify the role of these cytokines in osteoarthritis of dogs.<\/jats:p>\n<jats:p><jats:bold>SAMPLE<\/jats:bold> Pooled chondrocytes isolated from the stifle joints of 4 adult dogs.<\/jats:p>\n<jats:p><jats:bold>PROCEDURES<\/jats:bold> Chondrocytes were isolated, cultured, and frozen at \u221280\u00b0C. Pooled cells were incubated in medium with or without TGF-\u03b2 (1 or 10 ng\/mL) and subsequently stimulated with IL-1\u03b2 (10 ng\/mL). Concentrations of nitric oxide (NO) and prostaglandin (PG) E were measured in culture supernatants. Gene expression of matrix metalloproteinase (MMP)-3, tissue inhibitor of metalloproteinase (TIMP)-2, inducible NO synthase (iNOS), and cyclooxygenase (COX)-2 was quantified by use of real-time quantitative PCR assays.<\/jats:p>\n<jats:p><jats:bold>RESULTS<\/jats:bold> Stimulation with IL-1\u03b2 increased gene expression of all inflammatory markers, except for TIMP-2. Incubation with TGF-\u03b2 resulted in a significant decrease in MMP-3 and TIMP-2 mRNA concentrations but had no effect on PGE and NO concentrations. For cells treated with TGF-\u03b2 followed by IL-1\u03b2, concentrations of PGE and NO were lower, compared with concentrations for IL-1\u03b2 control cells. Furthermore, IL-1\u03b2\u2013induced gene expression of iNOS, MMP-3, and COX-2 was downregulated. However, the IL-1\u03b2\u2013induced downregulation of TIMP-2 gene expression was partially restored by pretreatment with TGF-\u03b2.<\/jats:p>\n<jats:p><jats:bold>CONCLUSIONS AND CLINICAL RELEVANCE<\/jats:bold> Results indicated that IL-1\u03b2 increased the expression of inflammatory genes and mediators, and TGF-\u03b2 largely attenuated the IL-1\u03b2\u2013mediated inflammatory response. Therefore, TGF-\u03b2 might be a novel target for use in the prevention and treatment of cartilage breakdown in dogs with osteoarthritis.<\/jats:p>","DOI":"10.2460\/ajvr.78.11.1264","type":"journal-article","created":{"date-parts":[[2017,10,27]],"date-time":"2017-10-27T12:27:46Z","timestamp":1509107266000},"page":"1264-1272","source":"Crossref","is-referenced-by-count":10,"title":["Effects of transforming growth factor-\u03b2 and interleukin-1\u03b2 on inflammatory markers of osteoarthritis in cultured canine chondrocytes"],"prefix":"10.2460","volume":"78","author":[{"given":"Nadja","family":"Adler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Schoeniger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herbert","family":"Fuhrmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1272","reference":[{"key":"ref1","series-title":"Akt Rheumatol","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1055\/s-2005-858868","article-title":"Physiologie und Pathophysiologie des Gelenkknorpels","volume":"30","author":"Pfander","year":"2005"},{"key":"ref2","series-title":"Curr Rheumatol Rep","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1007\/s11926-013-0375-6","article-title":"Homeostatic mechanisms in articular cartilage and role of inflammation in osteoarthritis","volume":"15","author":"Houard","year":"2013"},{"key":"ref3","series-title":"Vet Clin North Am Small Anim Pract","first-page":"699","article-title":"Osteoarthritis. Joint anatomy, physiology, and pathobiology","volume":"27","author":"Johnston","year":"1997"},{"key":"ref4","series-title":"Am J Vet Res","doi-asserted-by":"publisher","first-page":"983","DOI":"10.2460\/ajvr.74.7.983","article-title":"Modulation of inflammation and oxidative stress in canine chondrocytes","volume":"74","author":"Dycus","year":"2013"},{"key":"ref5","series-title":"Cytokine","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.cyto.2008.02.004","article-title":"Quantification of cytokines and inflammatory mediators in a three-dimensional model of inflammatory arthritis","volume":"42","author":"Rai","year":"2008"},{"key":"ref6","series-title":"Am J Vet Res","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.2460\/ajvr.2005.66.1187","article-title":"Effects of proinflammatory cytokines on canine articular chondrocytes in a three-dimensional culture","volume":"66","author":"Kuroki","year":"2005"},{"key":"ref7","series-title":"Am J Vet Res","doi-asserted-by":"publisher","first-page":"766","DOI":"10.2460\/ajvr.2000.61.766","article-title":"Effects of human recombinant interleukin-1 beta on canine articular chondrocytes in three-dimensional culture","volume":"61","author":"Cook","year":"2000"},{"key":"ref8","series-title":"Mediators Inflamm","first-page":"561459","article-title":"The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis","volume":"2014","author":"Wojdasiewicz","year":"2014"},{"key":"ref9","series-title":"Osteoarthritis Cartilage","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1016\/j.joca.2006.01.008","article-title":"Activation by IL-1 of bovine articular chondrocytes in culture within a 3-D collagen-based scaffold. An in vitro model to address the effect of compounds with therapeutic potential in osteoarthritis","volume":"14","author":"Cortial","year":"2006"},{"key":"ref10","series-title":"Arthritis Rheum","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1002\/art.20725","article-title":"Freshly isolated osteoarthritic chondrocytes are catabolically more active than normal chondrocytes, but less responsive to catabolic stimulation with interleukin-1beta","volume":"52","author":"Fan","year":"2005"},{"key":"ref11","series-title":"Arthritis Rheum","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1002\/art.20776","article-title":"Role of interleukin-1 and tumor necrosis factor alpha in matrix degradation of human osteoarthritic cartilage","volume":"52","author":"Kobayashi","year":"2005"},{"key":"ref12","series-title":"Proc Assoc Am Physicians","first-page":"65","article-title":"Autocrine production of IL-1 beta by human osteoarthritis-affected cartilage and differential regulation of endogenous nitric oxide, IL-6, prostaglandin E2, and IL-8","volume":"110","author":"Attur","year":"1998"},{"key":"ref13","series-title":"Osteoarthritis Cartilage","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/S1063-4584(96)80009-4","article-title":"The increased synthesis of inducible nitric oxide inhibits IL-1ra synthesis by human articular chondrocytes: possible role in osteoarthritic cartilage degradation","volume":"4","author":"Pelletier","year":"1996"},{"key":"ref14","series-title":"J Immunol","first-page":"4018","article-title":"Differentiation-dependent effects of IL-1 and TGF-beta on human articular chondrocyte proliferation are related to inducible nitric oxide synthase expression","volume":"154","author":"Blanco","year":"1995"},{"key":"ref15","series-title":"Ann Rheum Dis","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1136\/ard.2002.003749","article-title":"Tenascin and aggrecan expression by articular chondrocytes is influenced by interleukin 1beta: a possible explanation for the changes in matrix synthesis during osteoarthritis","volume":"63","author":"Pfander","year":"2004"},{"key":"ref16","series-title":"J Clin Invest","doi-asserted-by":"publisher","first-page":"2026","DOI":"10.1172\/JCI113823","article-title":"Interleukin 1 suppresses expression of cartilage-specific types II and IX collagens and increases types I and III collagens in human chondrocytes","volume":"82","author":"Goldring","year":"1988"},{"key":"ref17","series-title":"Arthritis Rheum","doi-asserted-by":"publisher","first-page":"3533","DOI":"10.1002\/art.22174","article-title":"Large-scale gene expression profiling reveals major pathogenetic pathways of cartilage degeneration in osteoarthritis","volume":"54","author":"Aigner","year":"2006"},{"key":"ref18","series-title":"Arthritis Rheum","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1002\/1529-0131(200105)44:5<1056::AID-ANR186>3.0.CO;2-U","article-title":"The role of C\u2013C chemokines and their receptors in osteoarthritis","volume":"44","author":"Yuan","year":"2001"},{"key":"ref19","series-title":"Cell Tissue Bank","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1007\/s10561-014-9472-7","article-title":"Alternative protocols to induce chondrogenic differentiation: transforming growth factor-beta superfamily","volume":"16","author":"Cicione","year":"2015"},{"key":"ref20","series-title":"Histochem Cell Biol","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1007\/s00418-007-0337-z","article-title":"Chondrogenesis, osteogenesis and adipogenesis of canine mesenchymal stem cells: a biochemical, morphological and ultrastructural study","volume":"128","author":"Csaki","year":"2007"},{"key":"ref21","series-title":"Mol Cell Biochem","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1023\/A:1006947015094","article-title":"Differential effects of interleukin-1 and transforming growth factor beta on the synthesis of small proteoglycans by rabbit articular chondrocytes cultured in alginate beads as compared to monolayers","volume":"199","author":"Demoor-Fossard","year":"1999"},{"key":"ref22","series-title":"Clin Orthop Relat Res","doi-asserted-by":"publisher","first-page":"S171","DOI":"10.1097\/00003086-200110001-00017","article-title":"Chondrogenesis in cartilage repair is induced by members of the transforming growth factor-beta superfamily","volume":"391","author":"Hunziker","year":"2001"},{"key":"ref23","series-title":"Connect Tissue Res","doi-asserted-by":"publisher","first-page":"190","DOI":"10.3109\/03008207.2015.1121250","article-title":"Identification of genes required for the spontaneous repair of partial-thickness cartilage defects in immature rats","volume":"57","author":"Ikegawa","year":"2016"},{"key":"ref24","series-title":"Inflamm Res","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1007\/s00011-005-1373-6","article-title":"TGF beta inhibits IL-1-induced iNOS expression and NO production in immortalized chondrocytes","volume":"54","author":"Vuolteenaho","year":"2005"},{"key":"ref25","series-title":"DNA Cell Biol","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1089\/dna.1996.15.1039","article-title":"Regulation of tissue inhibitor of metalloproteinases-3 gene expression by transforming growth factor-beta and dexamethasone in bovine and human articular chondrocytes","volume":"15","author":"Su","year":"1996"},{"key":"ref26","series-title":"Exp Cell Res","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1016\/0014-4827(91)90387-A","article-title":"Transforming growth factor-beta inhibition of interleukin-1 activity involves down-regulation of interleukin-1 receptors on chondrocytes","volume":"195","author":"Harvey","year":"1991"},{"key":"ref27","series-title":"J Rheumatol Suppl","first-page":"76","article-title":"Role of cytokines in osteoarthritis: comparative effects of interleukin 1 and transforming growth factor-beta on cultured rabbit articular chondrocytes","volume":"27","author":"Pujol","year":"1991"},{"key":"ref28","series-title":"Osteoarthritis Cartilage","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.joca.2003.11.009","article-title":"Effects of transforming growth factor-beta on aggrecanase production and proteoglycan degradation by human chondrocytes in vitro","volume":"12","author":"Moulharat","year":"2004"},{"key":"ref29","series-title":"Arthritis Rheum","doi-asserted-by":"publisher","first-page":"1653","DOI":"10.1002\/art.1780400915","article-title":"Collagenase-3 (matrix metalloprotease 13) is preferentially localized in the deep layer of human arthritic cartilage in situ: in vitro mimicking effect by transforming growth factor beta","volume":"40","author":"Moldovan","year":"1997"},{"key":"ref30","series-title":"J Immunol","doi-asserted-by":"publisher","first-page":"507","DOI":"10.4049\/jimmunol.169.1.507","article-title":"Inhibition of endogenous TGF-beta during experimental osteoarthritis prevents osteophyte formation and impairs cartilage repair","volume":"169","author":"Scharstuhl","year":"2002"},{"key":"ref31","series-title":"Osteoarthritis Cartilage","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1053\/joca.1999.0267","article-title":"Osteoarthritis-like changes in the murine knee joint resulting from intra-articular transforming growth factor-beta injections","volume":"8","author":"van Beuningen","year":"2000"},{"key":"ref32","series-title":"Bone Joint J","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1302\/0301-620X.97B7.35852","article-title":"A placebo-controlled randomised trial to assess the effect of TGF-beta 1-expressing chondrocytes in patients with arthritis of the knee","volume":"97-B","author":"Lee","year":"2015"},{"key":"ref33","series-title":"Orthopade","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1007\/s00132-003-0505-3","article-title":"Molekulare Charakterisierung von gez\u00fcchteten humanen dreidimensionalen Chondrozytentransplantaten","volume":"33","author":"Kaps","year":"2004"},{"key":"ref34","series-title":"Osteoarthritis Cartilage","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.joca.2004.11.005","article-title":"Characterizing osteochondrosis in the dog: potential roles for matrix metalloproteinases and mechanical load in pathogenesis and disease progression","volume":"13","author":"Kuroki","year":"2005"},{"key":"ref35","series-title":"J Comp Pathol","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.jcpa.2009.01.001","article-title":"Expression of genes encoding matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in normal and diseased canine mitral valves","volume":"140","author":"Aupperle","year":"2009"},{"key":"ref36","series-title":"Vet Immunol Immunopathol","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.vetimm.2006.10.004","article-title":"Dogs with patent Dirofilaria immitis infection have higher expression of circulating IL-4, IL-10 and iNOS mRNA than those with occult infection","volume":"115","author":"Morch\u00f3n","year":"2007"},{"key":"ref37","series-title":"Vet Immunol Immunopathol","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.vetimm.2007.01.011","article-title":"Development and application of multiple internal reference (housekeeper) gene assays for accurate normalisation of canine gene expression studies","volume":"117","author":"Peters","year":"2007"},{"key":"ref38","series-title":"Tissue Eng Part A","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1089\/ten.tea.2009.0581","article-title":"Passaged adult chondrocytes can form engineered cartilage with functional mechanical properties: a canine model","volume":"16","author":"NG","year":"2010"},{"key":"ref39","series-title":"Res Vet Sci","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/j.rvsc.2009.04.008","article-title":"Molecular and phenotypic modulations of primary and immortalized canine chondrocytes in different culture systems","volume":"87","author":"Rai","year":"2009"},{"key":"ref40","series-title":"Arthritis Rheum","doi-asserted-by":"publisher","first-page":"3107","DOI":"10.1002\/art.38122","article-title":"Deletion of the transforming growth factor beta receptor type II gene in articular chondrocytes leads to a progressive osteoarthritis-like phenotype in mice","volume":"65","author":"Shen","year":"2013"},{"key":"ref41","series-title":"Agents Actions","doi-asserted-by":"publisher","first-page":"C198","DOI":"10.1007\/BF01987636","article-title":"The effect of interleukin-1 beta and transforming growth factor beta on cathepsin B acitivity in human articular","volume":"41","author":"Mejiers","year":"1994"},{"key":"ref42","series-title":"Br J Rheumatol","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1093\/rheumatology\/36.7.729","article-title":"Effects of transforming growth factor beta on the production of prostaglandin E and caseinase activity of unstimulated and interleukin 1-stimulated human articular chondrocytes in culture","volume":"36","author":"Fawthrop","year":"1997"},{"key":"ref43","series-title":"Am J Vet Res","doi-asserted-by":"publisher","first-page":"2028","DOI":"10.2460\/ajvr.2005.66.2028","article-title":"Direct and indirect markers of cartilage metabolism in synovial fluid obtained from dogs with hip dysplasia and correlation with clinical and radiographic variables","volume":"66","author":"Fujita","year":"2005"},{"key":"ref44","series-title":"Osteoarthritis Cartilage","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1053\/joca.2002.0820","article-title":"Biomarkers of joint tissue metabolism in canine osteoarthritic and arthritic joint disorders","volume":"10","author":"Hegemann","year":"2002"},{"issue":"suppl 4","key":"ref45","series-title":"Ann Rheum Dis","first-page":"iv44","article-title":"What are the roles of metalloproteinases in cartilage and bone damage?","volume":"64","author":"Murphy","year":"2005"},{"key":"ref46","series-title":"Vet J","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/S1090-0233(00)90467-2","article-title":"Canine TIMP-2: purification, characterization and molecular detection","volume":"160","author":"Bee","year":"2000"},{"key":"ref47","series-title":"Nature","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1038\/37995","article-title":"Mechanism of inhibition of the human matrix metalloproteinase stromelysin-1 by TIMP-1","volume":"389","author":"Gomis-R\u00fcth","year":"1997"},{"key":"ref48","series-title":"Proc Natl Acad Sci U S A","doi-asserted-by":"publisher","first-page":"16898","DOI":"10.1073\/pnas.0702761104","article-title":"Nitric oxide regulates matrix metalloproteinase-9 activity by guanylyl-cyclase-dependent and -independent pathways","volume":"104","author":"Ridnour","year":"2007"},{"key":"ref49","series-title":"FASEB J","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1096\/fj.03-1096fje","article-title":"Peroxynitrite mediates calcium-dependent mitochondrial dysfunction and cell death via activation of calpains","volume":"18","author":"Whiteman","year":"2004"},{"key":"ref50","series-title":"J Immunol","doi-asserted-by":"publisher","first-page":"5082","DOI":"10.4049\/jimmunol.181.7.5082","article-title":"Prostaglandin E2 exerts catabolic effects in osteoarthritis cartilage: evidence for signaling via the EP4 receptor","volume":"181","author":"Attur","year":"2008"},{"key":"ref51","series-title":"Arthritis Res Ther","first-page":"R75","article-title":"Prostaglandin PGE(2) at very low concentrations suppresses collagen cleavage in cultured human osteoarthritic articular cartilage: this involves a decrease in expression of proinflammatory genes, collagenases and COL10A1, a gene linked to chondrocyte hypertrophy","volume":"9","author":"Tchetina","year":"2007"},{"key":"ref52","series-title":"Vet Immunol Immunopathol","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/S0165-2427(99)00052-5","article-title":"Effect of age, breed and dietary omega-6 (n-6): omega-3 (n-3) fatty acid ratio on immune function, eicosanoid production, and lipid peroxidation in young and aged dogs","volume":"69","author":"Kearns","year":"1999"},{"key":"ref53","series-title":"Arthritis Rheum","doi-asserted-by":"publisher","first-page":"3020","DOI":"10.1002\/art.22840","article-title":"Interleukin-1beta impairment of transforming growth factor beta1 signaling by down-regulation of transforming growth factor beta receptor type II and up-regulation of Smad7 in human articular chondrocytes","volume":"56","author":"Baug\u00e9","year":"2007"},{"key":"ref54","series-title":"Arthritis Rheum","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1002\/art.1780360108","article-title":"Transforming growth factor beta exerts opposite effects from interleukin-1 beta on cultured rabbit articular chondrocytes through reduction of interleukin-1 receptor expression","volume":"36","author":"R\u00e9dini","year":"1993"},{"issue":"suppl","key":"ref55","series-title":"Biomed Mater Eng","first-page":"75","article-title":"Age-related alterations in TGF beta signaling as a causal factor of cartilage degeneration in osteoarthritis","volume":"24","author":"van der Kraan","year":"2014"},{"key":"ref56","series-title":"Arthritis Res Ther","doi-asserted-by":"publisher","first-page":"R1338","DOI":"10.1186\/ar1833","article-title":"Reduced transforming growth factor-beta signaling in cartilage of old mice: role in impaired repair capacity","volume":"7","author":"Blaney Davidson","year":"2005"}],"container-title":["American Journal of Veterinary 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