Human genome-wide expression analysis reorients the study of inflammatory mediators and biomechanics in osteoarthritis.


:A major objective of this article is to examine the research implications of recently available genome-wide expression profiles of cartilage from human osteoarthritis (OA) joints. We propose that, when viewed in the light of extensive earlier work, this novel data provides a unique opportunity to reorient the design of experimental systems toward clinical relevance. Specifically, in the area of cartilage explant biology, this will require a fresh evaluation of existing paradigms, so as to optimize the choices of tissue source, cytokine/growth factor/nutrient addition, and biomechanical environment for discovery. Within this context, we firstly discuss the literature on the nature and role of potential catabolic mediators in OA pathology, including data from human OA cartilage, animal models of OA, and ex vivo studies. Secondly, due to the number and breadth of studies on IL-1β in this area, a major focus of the article is a critical analysis of the design and interpretation of cartilage studies where IL-1β has been used as a model cytokine. Thirdly, the article provides a data-driven perspective (including genome-wide analysis of clinical samples, studies on mutant mice, and clinical trials), which concludes that IL-1β should be replaced by soluble mediators such as IL-17 or TGF-β1, which are much more likely to mimic the disease in OA model systems. We also discuss the evidence that changes in early OA can be attributed to the activity of such soluble mediators, whereas late-stage disease results more from a chronic biomechanical effect on the matrix and cells of the remaining cartilage and on other local mediator-secreting cells. Lastly, an updated protocol for in vitro studies with cartilage explants and chondrocytes (including the use of specific gene expression arrays) is provided to motivate more disease-relevant studies on the interplay of cytokines, growth factors, and biomechanics on cellular behavior.


Sandy JD,Chan DD,Trevino RL,Wimmer MA,Plaas A




Has Abstract


2015-11-01 00:00:00














  • Systematic review and meta-analysis of the reliability and discriminative validity of cartilage compositional MRI in knee osteoarthritis.

    abstract:OBJECTIVE:To assess reliability and discriminative validity of cartilage compositional magnetic resonance imaging (MRI) in knee osteoarthritis (OA). DESIGN:The study was carried out per PRISMA recommendations. We searched MEDLINE and EMBASE (1974 - present) for eligible studies. We performed qualitative synthesis of r...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章,meta分析


    authors: MacKay JW,Low SBL,Smith TO,Toms AP,McCaskie AW,Gilbert FJ

    更新日期:2018-09-01 00:00:00

  • Site-dependent changes in structure and function of lapine articular cartilage 4 weeks after anterior cruciate ligament transection.

    abstract:OBJECTIVE:The aim of this study was to investigate the site-dependent changes in the structure and function of articular cartilage in the lapine knee joint at a very early stage of osteoarthritis (OA), created experimentally by anterior cruciate ligament transection (ACLT). METHODS:Unilateral ACLT was performed in eig...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Mäkelä JT,Rezaeian ZS,Mikkonen S,Madden R,Han SK,Jurvelin JS,Herzog W,Korhonen RK

    更新日期:2014-06-01 00:00:00

  • Multimodality scoring of chondral injuries in the equine fetlock joint ex vivo.

    abstract:OBJECTIVE:We investigate the potential of a prototype multimodality arthroscope, combining ultrasound, optical coherence tomography (OCT) and arthroscopic indentation device, for assessing cartilage lesions, and compare the reliability of this approach with conventional arthroscopic scoring ex vivo. DESIGN:Areas of in...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Sarin JK,Brommer H,Argüelles D,Puhakka PH,Inkinen SI,Afara IO,Saarakkala S,Töyräs J

    更新日期:2017-05-01 00:00:00

  • Standardization of nutrient media for isolated human articular chondrocytes in gelified agarose suspension culture.

    abstract::Human articular cartilage cells were cultured in 1.5% agarose in Dulbecco's modified Eagle's medium (DMEM) with 10% fetal calf serum or in serum-free DMEM with 0.15% bovine serum albumin. 35S-aggrecan synthesis in serum-free DMEM was between 20% and 30% of the value observed in DMEM supplemented with 10% fetal calf se...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Verbruggen G,Malfait AM,Dewulf M,Broddelez C,Veys EM

    更新日期:1995-12-01 00:00:00

  • Tibial cancellous bone changes in patients with knee osteoarthritis. A short-term longitudinal study using Fractal Signature Analysis.

    abstract:OBJECTIVE:To quantify tibial cancellous bone changes over 24 months in patients with medial compartment knee osteoarthritis (OA) subdivided into those with slow or detectable joint space narrowing (JSN). METHOD:Digitised macroradiographs (4x) were obtained at baseline and 24 months from 40 patients (F:26) and subdivid...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Messent EA,Ward RJ,Tonkin CJ,Buckland-Wright C

    更新日期:2005-06-01 00:00:00

  • Effect of adenovirus-mediated overexpression of bovine ADAMTS-4 and human ADAMTS-5 in primary bovine articular chondrocyte pellet culture system.

    abstract:INTRODUCTION:Articular cartilage matrix synthesis and degradation are dynamic processes that must be balanced for proper maintenance of the tissue. In osteoarthritis (OA), this balance is skewed toward degradation and ultimate loss of matrix. The transcriptional and/or activity levels of hundreds of genes are dysregula...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Arai M,Anderson D,Kurdi Y,Annis-Freeman B,Shields K,Collins-Racie LA,Corcoran C,DiBlasio-Smith E,Pittman DD,Dorner AJ,Morris E,LaVallie ER

    更新日期:2004-08-01 00:00:00

  • Gene expression profiling of chondrocytes from a porcine impact injury model.

    abstract:OBJECTIVE:To identify differentially expressed genes between axially impacted and control articular cartilage taken from porcine patellae maintained in organ culture for 14 days. METHODS:Porcine patellae were impacted perpendicular to the articular surface to create an impact injury. Intact patellae (control and impac...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Ashwell MS,O'Nan AT,Gonda MG,Mente PL

    更新日期:2008-08-01 00:00:00

  • Associations between pre-operative radiographic changes and outcomes after total knee joint replacement for osteoarthritis.

    abstract:OBJECTIVE:To assess the influence of pre-operative X-ray changes on the response to total knee joint replacement (TKR). METHODS:We included patients from one centre who underwent primary TKR (n = 478) for osteoarthritis in 2006 and 2007. The International Knee Society score (IKSS) and short form health survey were col...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Dowsey MM,Nikpour M,Dieppe P,Choong PF

    更新日期:2012-10-01 00:00:00

  • Depletion of SIRT6 causes cellular senescence, DNA damage, and telomere dysfunction in human chondrocytes.

    abstract:OBJECTIVE:SIRT6, a member of the sirtuin family of nicotinamide adenine dinucleotide (NAD(+))-dependent protein deacetylases, has been implicated as a key factor in aging-related diseases. However, the role of SIRT6 in chondrocytes has not been fully explored. The purpose of this study was to examine the role of SIRT6 ...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Nagai K,Matsushita T,Matsuzaki T,Takayama K,Matsumoto T,Kuroda R,Kurosaka M

    更新日期:2015-08-01 00:00:00

  • Differences in the repair process of longitudinal and transverse injuries of cartilage in the rat knee.

    abstract:OBJECTIVE:To clarify the relationship between type or direction of cartilage injury and its repair process, we investigated defects produced in rat knees histologically, immunohistochemically, and histomorphometrically. METHODS:A full-thickness cartilage injury (1 mm wide and 5 mm long) was produced on the patellar gr...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Yoshioka M,Kubo T,Coutts RD,Hirasawa Y

    更新日期:1998-01-01 00:00:00

  • Osteoarthritis of the knee after meniscal resection: long term radiographic evaluation of disease progression.

    abstract:OBJECTIVE:To determine prevalence, incidence and progression of radiographic knee osteoarthritis (OA) in a cohort of subjects with previous meniscectomy. METHODS:We assessed 221 subjects (177 men and 44 women) with weight bearing knee radiography twice (assessment A and B) with a follow-up time ranging from 4 to 10 ye...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Paradowski PT,Lohmander LS,Englund M

    更新日期:2016-05-01 00:00:00

  • Osteoarthritis-related difficulty walking and risk for diabetes complications.

    abstract:OBJECTIVES:To examine the effect of Osteoarthritis (OA)-related difficulty walking on risk for diabetes complications in persons with diabetes and OA. DESIGN:A population cohort aged 55+ years with symptomatic hip and knee OA was recruited 1996-98 and followed through provincial administrative data to 2015 (n = 2,225)...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Hawker GA,Croxford R,Bierman AS,Harvey P,Ravi B,Kendzerska T,Stanaitis I,King LK,Lipscombe L

    更新日期:2017-01-01 00:00:00

  • Relationship between structural pathology and pain behaviour in a model of osteoarthritis (OA).

    abstract:OBJECTIVES:To address the hypothesis that different types of established osteoarthritis (OA) pain behaviours have associations with different aspects of articular pathology, we investigated the relationship between structural knee joint pathology and pain behaviour following injection of a low vs a high dose of monosod...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Nwosu LN,Mapp PI,Chapman V,Walsh DA

    更新日期:2016-11-01 00:00:00

  • A static, closed and scaffold-free bioreactor system that permits chondrogenesis in vitro.

    abstract:OBJECTIVE:To characterise in vitro engineered cartilaginous constructs made employing a novel static, scaffold-free and closed chamber system. DESIGN:Chondrocytes derived from slaughter age pigs (3-6 months) were seeded at high density (20 x 10(6)) into cylindrical chambers (1.0 x 0.5cm) and were maintained between an...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Grogan SP,Rieser F,Winkelmann V,Berardi S,Mainil-Varlet P

    更新日期:2003-06-01 00:00:00

  • Precision and accuracy of joint space width measurements of the medial compartment of the knee using standardized MTP semi-flexed radiographs.

    abstract:OBJECTIVE:To quantify the precision and accuracy of measurements of joint space width (JSW) and joint space narrowing (JSN) from the medial tibiofemoral compartment of knee radiographs using a simple and easily adaptable protocol. METHODS:Radiographs of a caliper (a surrogate for JSW) were obtained to determine the pr...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Dupuis DE,Beynnon BD,Richard MJ,Novotny JE,Skelly JM,Cooper SM

    更新日期:2003-10-01 00:00:00

  • Expression of vitamin D receptors and matrix metalloproteinases in osteoarthritic cartilage and human articular chondrocytes in vitro.

    abstract:OBJECTIVES:To examine the in situ distributions of vitamin D receptors (VDR) and matrix metalloproteinases (MMPs) in osteoarthritic cartilage for comparison with non-arthritic, normal cartilage; and to assess the in vitro effects of 1alpha,25 dihydroxyvitaminD(3)(1alpha,25(OH)(2)D(3)) on MMPs-1, -3 and -9 and prostagla...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Tetlow LC,Woolley DE

    更新日期:2001-07-01 00:00:00

  • Prevalence of cam and pincer-type deformities on hip MRI in an asymptomatic young Swiss female population: a cross-sectional study.

    abstract:OBJECTIVES:Femoroacetabular impingement is proposed to cause early osteoarthritis (OA) in the non-dysplastic hip. We previously reported on the prevalence of femoral deformities in a young asymptomatic male population. The aim of this study was to determine the prevalence of both femoral and acetabular types of impinge...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Leunig M,Jüni P,Werlen S,Limacher A,Nüesch E,Pfirrmann CW,Trelle S,Odermatt A,Hofstetter W,Ganz R,Reichenbach S

    更新日期:2013-04-01 00:00:00

  • Joint-dependent response to impact and implications for post-traumatic osteoarthritis.

    abstract:OBJECTIVE:The prevalence of osteoarthritis (OA) varies between joints. Cartilage in eight different joints was evaluated to elucidate the disparate susceptibilities between joints to post-traumatic OA (PTOA) and provide evidence for joint-specific clinical treatments. The hypothesis was that cartilage in different join...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Novakofski KD,Berg LC,Bronzini I,Bonnevie ED,Poland SG,Bonassar LJ,Fortier LA

    更新日期:2015-07-01 00:00:00

  • Early-onset osteoarthritis of mouse temporomandibular joint induced by partial discectomy.

    abstract:OBJECTIVE:The objective of this study is to characterize mouse temporomandibular joint (TMJ) following partial discectomy, since there is no documentation of whether or not partial discectomy can induce early-onset osteoarthritis (OA) in mouse TMJ. METHODS:Partial discs of TMJ in mice were removed by microsurgery. His...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Xu L,Polur I,Lim C,Servais JM,Dobeck J,Li Y,Olsen BR

    更新日期:2009-07-01 00:00:00

  • Ultrasonographic assessment of medial femoral cartilage deformation acutely following walking and running.

    abstract:OBJECTIVE:To determine the magnitude of medial femoral cartilage deformation using ultrasonography (US) following walking and running in healthy individuals. DESIGN:Twenty-five healthy participants with no history of osteoarthritis or knee injury volunteered for this study. Medial femoral cartilage thickness was asses...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Harkey MS,Blackburn JT,Davis H,Sierra-Arévalo L,Nissman D,Pietrosimone B

    更新日期:2017-06-01 00:00:00

  • Cytochrome c oxidase levels in chondrocytes during monolayer expansion and after return to three dimensional culture.

    abstract:OBJECTIVE:Here we investigate whether monolayer culture or culture at 21% oxygen influences activity of cytochrome c oxidase, the terminal enzyme in the respiratory chain whose activity is essential for oxidative metabolism and whether return to three dimensional (3-D) culture restores cytochrome c oxidase activity to ...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Boubriak OA,Brooks JT,Urban JP

    更新日期:2009-08-01 00:00:00

  • Varus thrust and knee frontal plane dynamic motion in persons with knee osteoarthritis.

    abstract:OBJECTIVE:Varus thrust visualized during walking is associated with a greater medial knee load and an increased risk of medial knee osteoarthritis (OA) progression. Little is known about how varus thrust presence determined by visual observation relates to quantitative gait kinematic data. We hypothesized that varus th...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Chang AH,Chmiel JS,Moisio KC,Almagor O,Zhang Y,Cahue S,Sharma L

    更新日期:2013-11-01 00:00:00

  • Purine receptors modulate chondrocyte extracellular inorganic pyrophosphate production.

    abstract:OBJECTIVE:Extracellular inorganic pyrophosphate (ePPi) plays a key role in the regulation of normal and pathologic mineralization. The purpose of this work was to evaluate the role of P1 and P2 purine receptors in modulating ePPi production by articular chondrocytes. METHODS:Porcine cartilage explants and chondrocyte ...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Rosenthal AK,Hempel D,Kurup IV,Masuda I,Ryan LM

    更新日期:2010-11-01 00:00:00

  • Time-lapse observation of the dedifferentiation process in mouse chondrocytes using chondrocyte-specific reporters.

    abstract:OBJECTIVE:When chondrocytes prepared from cartilage are expanded in monolayer culture, fibroblast-like cells gradually prevail. Although these prevailing fibroblast-like cells are believed to emerge because of the dedifferentiation of chondrocytes, the definite origin of the prevailing fibroblast-like cells has not bee...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Minegishi Y,Hosokawa K,Tsumaki N

    更新日期:2013-12-01 00:00:00

  • Pain, motor and gait assessment of murine osteoarthritis in a cruciate ligament transection model.

    abstract:OBJECTIVE:The major complaint of Osteoarthritis (OA) patients is pain. However, due to the nature of clinical studies and the limitation of animal studies, few studies have linked function impairment and behavioral changes in OA animal models to cartilage loss and histopathology. Our objective was to study surrogate ma...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Ruan MZ,Patel RM,Dawson BC,Jiang MM,Lee BH

    更新日期:2013-09-01 00:00:00

  • FrzB-2: a human secreted frizzled-related protein with a potential role in chondrocyte apoptosis.

    abstract:OBJECTIVE:To characterize a novel secreted frizzled-related protein (SFRP) and determine its tissue distribution at the mRNA and protein level. METHODS:The FrzB-2 gene was identified by expressed sequence tag (EST) analysis of human tissue-derived libraries. Tissue distribution of FrzB-2 mRNA was determined by Norther...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: James IE,Kumar S,Barnes MR,Gress CJ,Hand AT,Dodds RA,Connor JR,Bradley BR,Campbell DA,Grabill SE,Williams K,Blake SM,Gowen M,Lark MW

    更新日期:2000-11-01 00:00:00

  • Cartilage growth and remodeling: modulation of balance between proteoglycan and collagen network in vitro with beta-aminopropionitrile.

    abstract:OBJECTIVE:To examine the effect of beta-aminopropionitrile (BAPN), an inhibitor of lysyl oxidase, on growth and remodeling of immature articular cartilage in vitro. DESIGN:Immature bovine articular cartilage explants from the superficial and middle layers were cultured for 13 days in serum-containing medium with or wi...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Asanbaeva A,Masuda K,Thonar EJ,Klisch SM,Sah RL

    更新日期:2008-01-01 00:00:00

  • Human osteoarthritic synovium impacts chondrogenic differentiation of mesenchymal stem cells via macrophage polarisation state.

    abstract:OBJECTIVE:Mesenchymal stem cells (MSCs) are a promising cell type for the repair of damaged cartilage in osteoarthritis (OA). However, OA synovial fluid and factors secreted by synovium impede chondrogenic differentiation of MSCs, and the mechanism responsible for this effect remains unclear. In this study, we sought t...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Fahy N,de Vries-van Melle ML,Lehmann J,Wei W,Grotenhuis N,Farrell E,van der Kraan PM,Murphy JM,Bastiaansen-Jenniskens YM,van Osch GJ

    更新日期:2014-08-01 00:00:00

  • Overexpression of active TGF-beta-1 in the murine knee joint: evidence for synovial-layer-dependent chondro-osteophyte formation.

    abstract:OBJECTIVE:To investigate the impact of a prolonged and constant active TGF-beta expression by the synovial lining cells on cartilage and ligamentous joint structures in vivo. DESIGN:An adenoviral vector (AdTGF-beta1(223,225)) was used for the overexpression of active TGF-beta1 in knee joints of C57Bl/6 mice. RESULTS:...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Bakker AC,van de Loo FA,van Beuningen HM,Sime P,van Lent PL,van der Kraan PM,Richards CD,van den Berg WB

    更新日期:2001-02-01 00:00:00

  • Intra-articular sodium hyaluronate in osteoarthritis of the knee: a multicenter, double-blind study.

    abstract::The efficacy and the safety of intra-articular injections of sodium hyaluronate were studied in patients with osteoarthritis of the knee in a randomized multicenter double-blind study. Two hundred and nine patients received five injections of either 25 mg hyaluronate/2.5 ml (verum, N = 102) or 0.25 mg hyaluronate/2.5 ...

    journal_title:Osteoarthritis and cartilage

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验


    authors: Puhl W,Bernau A,Greiling H,Köpcke W,Pförringer W,Steck KJ,Zacher J,Scharf HP

    更新日期:1993-10-01 00:00:00