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














  • Regulation of inflammatory and catabolic responses to IL-1β in rat articular chondrocytes by microRNAs miR-122 and miR-451.

    abstract:OBJECTIVE:miR-122 stimulates proliferation of growth plate chondrocytes whereas miR-451 stimulates terminal differentiation and matrix turnover. Here, we examined the potential of these microRNA as regulators of articular chondrocytes using an in vitro model of osteoarthritis. METHODS:miR-122 and miR-451 presence in r...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Scott KM,Cohen DJ,Hays M,Nielson DW,Grinstaff MW,Lawson TB,Snyder BD,Boyan BD,Schwartz Z

    更新日期:2021-01-01 00:00:00

  • Reliability, reproducibility and variability of the traditional Histologic/Histochemical Grading System vs the new OARSI Osteoarthritis Cartilage Histopathology Assessment System.

    abstract:OBJECTIVE:For many years, the Histologic/Histochemical Grading System (HHGS) for osteoarthritis monitoring has been used as a histological scoring system for the quality of cartilage. There are, however, some limitations using this grading system. The goal of the investigation presented in this paper was to examine the...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Custers RJ,Creemers LB,Verbout AJ,van Rijen MH,Dhert WJ,Saris DB

    更新日期:2007-11-01 00:00:00

  • Differential response of porcine osteoblasts and chondrocytes in cell or tissue culture after 5-aminolevulinic acid-based photodynamic therapy.

    abstract:OBJECTIVE:Outcome in osteochondral allografting is limited by the immunological incompatibility of the grafted tissue. Based on a resistance of chondrocytes to photodynamic therapy in cell culture it is proposed that 5-aminolevulinic acid-based photodynamic therapy (5-ALA-PDT) might be used to inactivate bone while mai...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Bastian JD,Egli RJ,Ganz R,Hofstetter W,Leunig M

    更新日期:2009-04-01 00:00:00

  • In vivo serial joint space measurements during dynamic loading in a canine model of osteoarthritis.

    abstract:OBJECTIVE:To devise a reliable, sensitive method to measure joint space in vivo during dynamic loading. Additionally, to determine if dynamic joint space changes were related to the severity of long-term cartilage damage. DESIGN:Subjects were 23 adult foxhounds (18 experimental, 5 control). Experimental subjects had s...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Anderst WJ,Les C,Tashman S

    更新日期:2005-09-01 00:00:00

  • Subregional statistical shape modelling identifies lesser trochanter size as a possible risk factor for radiographic hip osteoarthritis, a cross-sectional analysis from the Osteoporotic Fractures in Men Study.

    abstract:OBJECTIVE:Statistical shape modelling (SSM) of hip dual-energy X-ray absorptiometry (DXA) scans has identified relationships between hip shape and radiographic hip OA (rHOA). We aimed to further elucidate shape characteristics related to rHOA by focusing on subregions identified from whole-hip shape models. METHOD:SSM...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Faber BG,Bredbenner TL,Baird D,Gregory J,Saunders F,Giuraniuc CV,Aspden RM,Lane NE,Orwoll E,Tobias JH,Osteoporotic Fractures in Men (MrOS) Study Research Group.

    更新日期:2020-08-01 00:00:00

  • Evidence for functional ATP-sensitive (K(ATP)) potassium channels in human and equine articular chondrocytes.

    abstract:OBJECTIVE:Chondrocytes are highly sensitive to variations in extracellular glucose and oxygen levels in the extracellular matrix. As such, they must possess a number of mechanisms to detect and respond to alterations in the metabolic state of cartilage. In other organs such as the pancreas, heart and brain, such detect...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Mobasheri A,Gent TC,Nash AI,Womack MD,Moskaluk CA,Barrett-Jolley R

    更新日期:2007-01-01 00:00:00

  • Effects of a 10-week toe-out gait modification intervention in people with medial knee osteoarthritis: a pilot, feasibility study.

    abstract:OBJECTIVE:To examine the feasibility of a 10-week gait modification program in people with medial tibiofemoral knee osteoarthritis (OA), and to assess changes in clinical and biomechanical outcomes. DESIGN:Fifteen people with medial knee OA completed 10 weeks of gait modification focusing on increasing toe-out angle d...

    journal_title:Osteoarthritis and cartilage

    pub_type: 临床试验,杂志文章


    authors: Hunt MA,Takacs J

    更新日期:2014-07-01 00:00:00

  • Expression and function of TbetaRII-B, a variant of the type II TGF-beta receptor, in human chondrocytes.

    abstract:OBJECTIVE:Transforming growth factor-beta (TGF-beta) has profound effects on chondrocyte proliferation and matrix production, and dysregulation of TGF-beta action has been implicated in osteoarthritis. The mechanisms by which the diverse actions of TGF-beta are regulated in chondrocytes are unclear. Although it is well...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Parker WL,Finnson KW,Soe-Lin H,Knaus P,Philip A

    更新日期:2007-04-01 00:00:00

  • 2D and 3D MOCART scoring systems assessed by 9.4 T high-field MRI correlate with elementary and complex histological scoring systems in a translational model of osteochondral repair.

    abstract:OBJECTIVE:To compare the 2D and 3D MOCART system obtained with 9.4 T high-field magnetic resonance imaging (MRI) for the ex vivo analysis of osteochondral repair in a translational model and to correlate the data with semiquantitative histological analysis. METHODS:Osteochondral samples representing all levels of repa...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Goebel L,Zurakowski D,Müller A,Pape D,Cucchiarini M,Madry H

    更新日期:2014-10-01 00:00:00

  • Distinct expression pattern of early- and late-response genes in normal and osteoarthritic human synovial membranes.

    abstract::The significance of activating proteins (AP-1), c-fos, c-jun and jun B relative to the AP-1 responsive metallothionein, collagenase and stromelysin gene expression in the pathophysiology of osteoarthritis (OA) was investigated. The 'early' c-fos, c-jun and jun-B mRNAs were ubiquitously expressed in normal and OA human...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Zafarullah M,Martel-Pelletier J,Cloutier JM,Gedamu L,Pelletier JP

    更新日期:1993-07-01 00:00:00

  • Modulation of inflammation by chondroitin sulfate.

    abstract:OBJECTIVE AND METHODS:To evaluate the immune-modulator effect of chondroitin sulfate (CS) by means of the review of the literature. RESULTS:Inflammatory reactions are primarily originated by infectious agents, immune reactions and by sterile tissue lesions that activate membrane receptors by means of pathogen-associat...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章,评审


    authors: Vallières M,du Souich P

    更新日期:2010-06-01 00:00:00

  • Analysis of changes in proteoglycan content in murine articular cartilage using image analysis.

    abstract::The extracellular matrix of articular cartilage consists mainly of type II collagen and large aggregating proteoglycan (aggrecan). During arthritis and other joint diseases, the proteoglycan (PG) level of cartilage matrix is diminished, leading to impairment of normal joint function. A new method is described for meas...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: van der Kraan PM,de Lange J,Vitters EL,van Beuningen HM,van Osch GJ,van Lent PL,van den Berg WB

    更新日期:1994-09-01 00:00:00

  • Evidence that meniscus damage may be a component of osteoarthritis: the Framingham study.

    abstract:OBJECTIVES:The etiology of degenerative meniscus tear is unclear but could be related to a generalized osteoarthritic disease process. We studied whether radiographic hand osteoarthritis (OA) is associated with meniscus damage. METHODS:We examined 974 persons aged 50-90 years drawn via census tract data and random-dig...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Englund M,Haugen IK,Guermazi A,Roemer FW,Niu J,Neogi T,Aliabadi P,Felson DT

    更新日期:2016-02-01 00:00:00

  • Changes in biomechanical properties of tendons and ligaments from joint disuse.

    abstract:OBJECTIVE:The purpose of this paper is to review changes in the biomechanical properties of tendons and ligaments from joint disuse. METHOD:We have reviewed 37 experimental studies on joint disuse, which have been carried out with various models of disuse and with various animals. RESULTS:Immobilization of joints has...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Yasuda K,Hayashi K

    更新日期:1999-01-01 00:00:00

  • Clinical feasibility of a novel biphasic osteochondral composite for matrix-associated autologous chondrocyte implantation.

    abstract:OBJECTIVE:Matrix-associated autologous chondrocyte implantation has been used to treat cartilage defects. We developed a biphasic cylindrical osteochondral composite construct for such use, and conducted this study to determine its feasibility for treating osteochondral lesions in human knees. METHOD:Ten patients with...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Chiang H,Liao CJ,Hsieh CH,Shen CY,Huang YY,Jiang CC

    更新日期:2013-04-01 00:00:00

  • Osteoarthritis year 2010 in review: pathomechanisms.

    abstract::Osteoarthritis is characterized by progressive breakdown of articular cartilage. This review summarizes findings of the last year, which shed new light on mechanisms and factors involved in cartilage loss. Evidence is accumulating that the transcription factor hypoxia-inducible factor-2α (HIF-2α) is highly enhanced in...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章,评审


    authors: van den Berg WB

    更新日期:2011-04-01 00:00:00

  • Perlecan in late stages of osteoarthritis of the human knee joint.

    abstract:OBJECTIVE:Disturbances of the proteoglycan metabolism play an essential role in the pathology of osteoarthritis. The extracellular matrix proteoglycan, perlecan, has lately been identified as a cell biological factor in cartilage development and maintenance. We investigated the tissue distribution of perlecan, the rela...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Tesche F,Miosge N

    更新日期:2004-11-01 00:00:00

  • Increased rate of hysterectomy in women undergoing surgery for osteoarthritis of the knee.

    abstract::We performed a case-controlled study to determine whether previous gynecological surgery is associated with severe osteoarthritis (OA) of the knee, the hip or the spine, as well as mild OA of the knee. Patients who underwent surgical treatment for OA were defined as having severe OA. Patients with knee pain and radiog...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Inoue K,Ushiyama T,Kim Y,Shichikawa K,Nishioka J,Hukuda S

    更新日期:1995-09-01 00:00:00

  • Skin and urine pentosidine weakly correlate with joint damage in a cohort of patients with early signs of osteoarthritis (CHECK).

    abstract:OBJECTIVES:Age-related changes in articular cartilage are likely to play a role in the aetiology of osteoarthritis (OA). One of the major age-related changes in cartilage is the accumulation of advanced-glycation-endproducts (AGEs). Since, cartilage tissue is not readily available from patients for studying AGE levels,...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章,多中心研究


    authors: Vos PA,DeGroot J,Huisman AM,Oostveen JC,Marijnissen AC,Bijlsma JW,van El B,Zuurmond AM,Lafeber FP

    更新日期:2010-10-01 00:00:00

  • The innate immune response as a mediator of osteoarthritis pain.

    abstract::In this narrative review, we discuss the emerging role of innate immunity in osteoarthritis (OA) joint pain. First, we give a brief description of the pain pathway in the context of OA. Then we consider how neuro-immune signaling pathways may promote OA pain. First, activation of neuronal Pattern Recognition Receptors...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章,评审


    authors: Miller RJ,Malfait AM,Miller RE

    更新日期:2020-05-01 00:00:00

  • The chemokine receptor CCR5 plays a role in post-traumatic cartilage loss in mice, but does not affect synovium and bone.

    abstract:OBJECTIVE:C-C chemokine receptor type 5 (CCR5) has been implicated in rheumatoid arthritis and several inflammatory diseases, where its blockade resulted in reduced joint destruction. However, its role in modulating cartilage and bone changes in post-traumatic osteoarthritis (OA) has not yet been investigated. In this ...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Takebe K,Rai MF,Schmidt EJ,Sandell LJ

    更新日期:2015-03-01 00:00:00

  • Osteoarthritis year 2012 in review: biomarkers.

    abstract:PURPOSE:Biomarkers provide useful diagnostic information by detecting cartilage degradation in osteoarthritis (OA), reflecting disease-relevant biological activity and predicting the course of disease progression. They also serve as surrogate endpoints in the drug discovery process. The aim of this narrative review was...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章,评审


    authors: Mobasheri A

    更新日期:2012-12-01 00:00:00

  • The response of elderly human articular cartilage to mechanical stimuli in vitro.

    abstract:OBJECTIVE:To investigate the biosynthetic response of elderly human femoral head articular cartilage to mechanical stimulation in vitro and its variation with site. METHOD:Full-depth cartilage biopsies of articular cartilage were removed from defined sites on 10 femoral heads from patients aged 68-95 years. Cartilage ...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Plumb MS,Aspden RM

    更新日期:2005-12-01 00:00:00

  • Modulation of bovine articular chondrocyte gene expression in vitro by oxygen tension.

    abstract:OBJECTIVE:Adult articular cartilage is a physiologically hypoxic tissue with a proposed gradient of oxygen tension ranging from <10% oxygen at the cartilage surface to <1% in the deepest layers. This gradient may be disturbed during diseases of the joint, for example in rheumatoid arthritis when synovial fluid pO(2)fal...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Grimshaw MJ,Mason RM

    更新日期:2001-05-01 00:00:00

  • A prospective, randomized, pragmatic, health outcomes trial evaluating the incorporation of hylan G-F 20 into the treatment paradigm for patients with knee osteoarthritis (Part 1 of 2): clinical results.

    abstract:OBJECTIVE:First, to assess the clinical effectiveness of hylan G-F 20 in an appropriate care treatment regimen (as defined by the American College of Rheumatology (ACR) 1995 guidelines) as measured by validated disease-specific outcomes and health-related quality of life endpoints for patients with osteoarthritis (OA) ...

    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: Raynauld JP,Torrance GW,Band PA,Goldsmith CH,Tugwell P,Walker V,Schultz M,Bellamy N,Canadian Knee OA Study Group.

    更新日期:2002-07-01 00:00:00

  • Occupational risk factors for osteoarthritis of the knee: a meta-analysis.

    abstract:INTRODUCTION:Systematic reviews agree that knee osteoarthritis (OA) is related to occupational activities, but have not quantified the overall risks. METHODS:Systematic review of observational studies of knee OA and occupation. Job titles, elite sport, heavy work, kneeling, and other activities were included. Relative...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章,meta分析,评审


    authors: McWilliams DF,Leeb BF,Muthuri SG,Doherty M,Zhang W

    更新日期:2011-07-01 00:00:00

  • Gene expression profiling following BMP-2 induction of mesenchymal chondrogenesis in vitro.

    abstract:OBJECTIVE:This study aims to apply gene expression profiling technology to gain insight into the molecular regulation of mesenchymal chondrogenesis. METHODS:The experimental system consists of micromass cultures of C3H10T1/2 cells, a murine multipotential embryonic cell line, treated with the chondroinductive growth f...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Izzo MW,Pucci B,Tuan RS,Hall DJ

    更新日期:2002-01-01 00:00:00

  • Symptoms of the knee and hip in individuals with and without limb length inequality.

    abstract:OBJECTIVE:This cross-sectional study examined the association of limb length inequality (LLI) with chronic joint symptoms at the hip and knee in a large, community-based sample, adjusting for the presence of radiographic osteoarthritis (OA) and other confounders. METHODS:The total study group comprised 3012 participan...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Golightly YM,Allen KD,Helmick CG,Renner JB,Jordan JM

    更新日期:2009-05-01 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

  • Fibromodulin-null murine knee joints display increased incidences of osteoarthritis and alterations in tissue biochemistry.

    abstract:OBJECTIVE:To elucidate variations in tissue ultrastructure and incidence of pathology between fibromodulin (FM)-null mice and wild-type (WT) animals. DESIGN:FM-null and WT siblings from different age groups were compared. Serial sections were made through paraffin-embedded whole knees and investigated histologically. ...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Gill MR,Oldberg A,Reinholt FP

    更新日期:2002-10-01 00:00:00