Elevated aggrecanase activity in a rat model of joint injury is attenuated by an aggrecanase specific inhibitor P.S. Chockalingam, W. Sun, M.A. Rivera-Bermudez,

Slides:

Advertisements

Similar presentations

Type II collagen C2C epitope in human synovial fluid and serum after knee injury – associations with molecular and structural markers of injury N. Kumahashi,

Advertisements

The association between metacarpal ratio, radiographic hand and knee osteoarthritis and its progression after meniscectomy P.T. Paradowski, L.S. Lohmander,

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is increased in osteoarthritis and regulates chondrocyte catabolic and anabolic activities

Pressure and inflammatory stimulation induced increase of cadherin-11 is mediated by PI3K/Akt pathway in synovial fibroblasts from temporomandibular joint

Western blot quantification of aggrecan fragments in human synovial fluid indicates differences in fragment patterns between joint diseases A. Struglics,

Development of a novel clinical biomarker assay to detect and quantify aggrecanase- generated aggrecan fragments in human synovial fluid, serum and urine

Comparing intra-articular CTXII levels assessed via magnetic capture or lavage in a rat knee osteoarthritis model E.G. Yarmola, Y.Y. Shah, H.E. Kloefkorn,

Anti-inflammatory effect of low intensity ultrasound (LIUS) on complete Freund's adjuvant-induced arthritis synovium J.-I. Chung, S. Barua, B.H. Choi,

MAPKs are essential upstream signaling pathways in proteolytic cartilage degradation – divergence in pathways leading to aggrecanase and MMP-mediated.

Long-term analgesic effect of a single dose of anti-NGF antibody on pain during motion without notable suppression of joint edema and lesion in a rat.

Loss of extracellular matrix from articular cartilage is mediated by the synovium and ligament after anterior cruciate ligament injury C.M. Haslauer,

Characterization of an ADAMTS-5-mediated cleavage site in aggrecan in OSM- stimulated bovine cartilage M. Durigova, M.Sc., P. Soucy, B.Sc., K. Fushimi,

Autophagy is activated in compression-induced cell degeneration and is mediated by reactive oxygen species in nucleus pulposus cells exposed to compression

MicroRNA221-3p modulates Ets-1 expression in synovial fibroblasts from patients with osteoarthritis of temporomandibular joint J. Xu, Y. Liu, M. Deng,

Prolonged trauma-induced increase of inflammatory cytokines in synovial fluid after surgical reconstruction of anterior cruciate ligament ruptures compared.

Surgical reconstruction of ruptured anterior cruciate ligament prolongs trauma-induced increase of inflammatory cytokines in synovial fluid: an exploratory.

Human osteoarthritis synovial fluid and joint cartilage contain both aggrecanase- and matrix metalloproteinase-generated aggrecan fragments A. Struglics,

M.J. Peffers, B. McDermott, P.D. Clegg, C.M. Riggs

A short-term pharmacodynamic model for monitoring aggrecanase activity: injection of monosodium iodoacetate (MIA) in rats and assessment of aggrecan neoepitope.

Nitric oxide enhances aggrecan degradation by aggrecanase in response to TNF-α but not IL-1β treatment at a post-transcriptional level in bovine cartilage.

Dr L. S. Kim, N. D. , Dr L. J. Axelrod, N. D. , Dr P. Howard, M. D

P.T. Paradowski, L.S. Lohmander, M. Englund

Desirable effect of combination therapy with high molecular weight hyaluronate and NSAIDs on MMP production M. Hashizume, M. Mihara Osteoarthritis and.

Evidence for enhanced collagen type III deposition focally in the territorial matrix of osteoarthritic hip articular cartilage S. Hosseininia, M.A. Weis,

The association between changes in synovial fluid levels of ARGS-aggrecan fragments, progression of radiographic osteoarthritis and self-reported outcomes:

Estimation of the identity of proteolytic aggrecan fragments using PAGE migration and Western immunoblot A. Struglics, Ph.D., S. Larsson, B.Sc., L.S.

An ARGS-aggrecan assay for analysis in blood and synovial fluid

Concentrations of synovial fluid biomarkers and the prediction of knee osteoarthritis 16 years after anterior cruciate ligament injury P. Neuman, L.E.

Increase in excitatory amino acid concentration and transporters expression in osteoarthritic knees of anterior cruciate ligament transected rabbits

Anti-inflammatory effect of low intensity ultrasound (LIUS) on complete Freund's adjuvant-induced arthritis synovium J.-I. Chung, S. Barua, B.H. Choi,

P.T. Paradowski, L.S. Lohmander, M. Englund

Cytokine induced metalloproteinase expression and activity does not correlate with focal susceptibility of articular cartilage to degeneration C.B. Little,

Changes in synovial fluid and serum concentrations of cartilage oligomeric matrix protein over five years after anterior cruciate ligament rupture A.

Quantitation OF ARGS aggrecan fragments in synovial fluid, serum and urine from osteoarthritis patients F.M. Germaschewski, C.J. Matheny, J. Larkin,

The use of hyperosmotic saline for chondroprotection: implications for orthopaedic surgery and cartilage repair N.M. Eltawil, S.E.M. Howie, A.H.R.W.

V. Queirolo, D. Galli, E. Masselli, R. M. Borzì, S. Martini, F

10mM glucosamine prevents activation of proADAMTS5 (aggrecanase-2) in transfected cells by interference with post-translational modification of furin

Synovial fluid levels of bradykinin correlate with biochemical markers for cartilage degradation and inflammation in knee osteoarthritis F. Bellucci,

Expression of the semicarbazide-sensitive amine oxidase in articular cartilage: its role in terminal differentiation of chondrocytes in rat and human

Evidence for two distinct pathways in TNFα-induced membrane and soluble forms of ICAM-1 in human osteoblast-like cells isolated from osteoarthritic patients

Tenascin-C levels in synovial fluid are elevated after injury to the human and canine joint and correlate with markers of inflammation and matrix degradation

Comparing intra-articular CTXII levels assessed via magnetic capture or lavage in a rat knee osteoarthritis model E.G. Yarmola, Y.Y. Shah, H.E. Kloefkorn,

Measurement of matrilin-3 levels in human serum and synovial fluid using a competitive enzyme-linked immunosorbent assay J.-B. Vincourt, P. Gillet, A.-C.

D. R. Seifer, B. A. , B. D. Furman, M. S. , F. Guilak, Ph. D. , S. A

Interleukin-1 is not involved in synovial inflammation and cartilage destruction in collagenase-induced osteoarthritis S.C.M. van Dalen, A.B. Blom, A.W.

Osteoarthritis year 2013 in review: genetics and genomics

Time to be positive about negative data?

Human aggrecanase generated synovial fluid fragment levels are elevated directly after knee injuries due to proteolysis both in the inter globular and.

Resistin is elevated following traumatic joint injury and causes matrix degradation and release of inflammatory cytokines from articular cartilage in.

J. Ranstam Osteoarthritis and Cartilage

Z. Lin, M. B. , N. J. Pavlos, B. Sc. (Hons. ), Ph. D. , M. A. Cake, B

Aggrecan fragments in the synovial fluid of osteoarthritis and juvenile idiopathic arthritis patients reveals differences in the specificity of aggrecanase.

H. Sadeghi, D.E.T. Shepherd, D.M. Espino Osteoarthritis and Cartilage

Osteoarthritis of the knee after meniscal resection: long term radiographic evaluation of disease progression P.T. Paradowski, L.S. Lohmander, M. Englund

C. -H. Chou, H. -G. Wisniewski, P. Band, J. Huebner, T. Stabler, C

Joint dependent concentrations of bone alkaline phosphatase in serum and synovial fluids of horses with osteochondral injury: an analytical and clinical.

Intra-articular injection of tumor necrosis factor-α in the rat: an acute and reversible in vivo model of cartilage proteoglycan degradation A.M. Malfait,

Activation of Indian hedgehog promotes chondrocyte hypertrophy and upregulation of MMP-13 in human osteoarthritic cartilage F. Wei, J. Zhou, X. Wei,

Characterization of proteoglycan production and processing by chondrocytes and BMSCs in tissue engineered constructs J.T. Connelly, Ph.D., C.G. Wilson,

Interleukin-6 and tumor necrosis factor alpha in synovial fluid are associated with progression of radiographic knee osteoarthritis in subjects with previous.

Analysis of ADAMTS4 and MT4-MMP indicates that both are involved in aggrecanolysis in interleukin-1-treated bovine cartilage P. Patwari, G. Gao, J.H.

The OARSI histopathology initiative – recommendations for histological assessments of osteoarthritis in the mouse S.S. Glasson, M.G. Chambers, W.B. Van.

A. Struglics, M. Hansson, L.S. Lohmander Osteoarthritis and Cartilage

S.G. Muthuri, D.F. McWilliams, M. Doherty, W. Zhang

Acute resistance exercise and pressure pain sensitivity in knee osteoarthritis: a randomised crossover trial N.J. Burrows, J. Booth, D.L. Sturnieks,

Osteoarthritis year 2012 in review: biology

Synovial fluid concentration of gremlin1 but not frizzled-related protein is increased in patients after acute knee injury L. Zhong, J. Leijten, J. Post,

Removal of O-linked and N-linked oligosaccharides is required for optimum detection of NITEGE neoepitope on ADAMTS4-digested fetal aggrecans: implications.

Measurement of synovial fluid volume using urea

A. Carlson, B. Bothner, R. June Osteoarthritis and Cartilage

Presentation transcript:

Elevated aggrecanase activity in a rat model of joint injury is attenuated by an aggrecanase specific inhibitor P.S. Chockalingam, W. Sun, M.A. Rivera-Bermudez, W. Zeng, D.R. Dufield, S. Larsson, L.S. Lohmander, C.R. Flannery, S.S. Glasson, K.E. Georgiadis, E.A. Morris Osteoarthritis and Cartilage Volume 19, Issue 3, Pages 315-323 (March 2011) DOI: 10.1016/j.joca.2010.12.004 Copyright © 2010 Osteoarthritis Research Society International Terms and Conditions

Fig. 1 (A) Western analysis of antibody binding to aggrecan: Human ARG-aggrecan standard and a D1 fraction of synovial fluid pool from OA patients were deglycosylated, separated on a 3–8% Tris-acetate SDS gel, blotted onto a PVDF membrane, and probed with AHP0022 (1:500), BC-3 (1:2000), or AGG-C1 (1:3000). C=Human ARG-aggrecan standard; SF=D1 fraction of synovial fluid pooled from OA patients. C and SF were loaded at the equivalent of 3μg sGAG for AHP0022 and BC-3 analysis. 5μg sGAG of C was loaded for AGG-C1 analysis. ARGS-G2-GVA in species 5 was observed only in the synovial fluid pool from OA patients and its identity was confirmed by anti-GVA analysis (data not shown; anti-GVA kindly provided by Dr Struglics, Lund). (B) Specificity of the ELISA: Rat aggrecan cleaved with ADAMTS4, deglycosylated (diamond); Uncleaved aggrecan, deglycosylated (circle); MMP-13 cleaved, deglycosylated (square); ADAMTS4 cleaved but not deglycosylated aggrecan (cross) were tested in the ARG-ELISA. Osteoarthritis and Cartilage 2011 19, 315-323DOI: (10.1016/j.joca.2010.12.004) Copyright © 2010 Osteoarthritis Research Society International Terms and Conditions

Fig. 2 Correlation between the ARG-aggrecan ELISA and the LC-MS/MS analysis for ARG-aggrecan quantitation in rat synovial fluid lavage samples from the rat MT model (n=28, rs from Spearman=0.95, P<0.0001). Osteoarthritis and Cartilage 2011 19, 315-323DOI: (10.1016/j.joca.2010.12.004) Copyright © 2010 Osteoarthritis Research Society International Terms and Conditions

Fig. 3 Time course of ARG-aggrecan release in the rat MT model. Rats were euthanized at different times after surgery (4 days–8 weeks, n=10 rats/time point). Five naive rats (10 joints) per time point were also included in the study. For each time point, 10 synovial fluid lavage samples from the right MT, left CL, and naive (N; left+right knees) joints were tested in the ARG-aggrecan ELISA and values corrected for dilution using serum urea levels. Average ARG-aggrecan with the error bars indicating 95% confidence intervals. No correction was made in statistical testing for naive right-left knees not being independent. P values are included in the graph. Osteoarthritis and Cartilage 2011 19, 315-323DOI: (10.1016/j.joca.2010.12.004) Copyright © 2010 Osteoarthritis Research Society International Terms and Conditions