Osteoarthritis and Cartilage - Articles in Press

Effects of intraarticular IL1-Ra for acute anterior cruciate ligament knee injury: a randomized controlled pilot trial (NCT00332254) - Corrected Proof

2012-02-03

Summary: Objective: To evaluate the clinical effectiveness of intraarticular IL-1 receptor antagonist (IL-1Ra) for anterior cruciate ligament (ACL) tear.Methods: Eleven patients with acute ACL tear confirmed by magnetic resonance imaging (MRI) were randomized to receive a single intraarticular injection of IL-1Ra (anakinra 150 mg, n = 6) or equal volume of saline placebo (1 ml, n = 5). The double-blinded treatment was administered a mean 2 weeks after injury. Synovial fluid (SF) (n = 9 patients) and sera (all patients) were available at baseline (prior to injection) and immediately prior to surgery (mean 35 days later) and analyzed for SF IL-1α, IL-1β, IL-1Ra and serum hyaluronan (HA), an indicator of synovial inflammation. The primary outcome, standardized Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire, was obtained at 0 (baseline), 4, and 14 days after injection.Results: Compared with placebo, the IL-1Ra group had substantially greater improvement in key outcomes over 14 days (KOOS pain P = 0.001; activities of daily living P = 0.0015; KOOS sports function P = 0.0026; KOOS quality of life (QOL) P = 0.0048; and total KOOS P < 0.0001). There were no adverse reactions in either group. SF IL-1α (P = 0.05) and serum HA (P = 0.03), but not IL-1β, or IL-1Ra, decreased significantly in the IL-1Ra but not the placebo treated patients. Compared with placebo, IL-1α was borderline significantly different in the IL-1Ra treated group (P = 0.06).Conclusions: Administered within the first month following severe knee injury, IL-1Ra reduced knee pain and improved function over a 2-week interval. This promising proof of concept study provides a new paradigm for studies of acute joint injury and suggests that a larger follow-up study is warranted.

Insulin-like growth factor-1 boosts the developing process of condylar hyperplasia by stimulating chondrocytes proliferation - Corrected Proof

Y. Chen, J. Ke, X. Long, Q. Meng, M. Deng, W. Fang, J. Li, H. Cai, S. Chen — 2012-02-03

Summary: Objective: The etiology of Condylar hyperplasia (CH) of human temporomandibular joint (TMJ) remains largely unknown. Our previous study has demonstrated that enriched insulin-like growth factor-1(IGF-1) was expressed in the proliferation and hypertrophic layers of CH cartilage. Accordingly, this study was aimed to investigate whether IGF-1 regulates CH chondrocytes proliferation in condylar cartilage overgrowth and explore the molecular mechanism of IGF-1 involved in.Methods: Chondrocytes were isolated from 6 CH and 3 normal cartilage (NC) specimens and cultured in alginate beads or monolayer, treated with IGF-1 or specific inhibitors such as 7-[trans-3-[(azetidin-1-yl)methyl]cyclobutyl]-5-(3-benzyloxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (NVP-AEW541), U0126, and LY294002. Thereafter, cellular proliferation capacity was evaluated by Cell Viability Analyzer (alginate beads culture) or 3-(4,5-dimethylthiazo(-2-yl)-2,5-diphenyltetrazolium bromide (MTT) (monolayer culture). Gene expression levels of IGF-1, IGF-1 receptor (IGF-1R), collagen type II, type X and those genes associated with proliferation were evaluated by realtime PCR. Protein levels of IGF-1 and IGF-1R synthesized by CH chondrocytes were accessed by enzyme-linked immunosorbent assay (ELISA) and western blotting.Results: CH chondrocytes enhanced cellular proliferation capacity and expressed significantly higher levels of messenger RNA (mRNA) and protein expressions of IGF-1 and IGF-1R, as compared with NC chondrocytes. Furthermore, enriched IGF-1 enhanced CH chondrocytes proliferation, up-regulated the expressions of specific genes associated with cellular proliferation and elevated the gene expression of collagen type II A1 (COL2A1). Besides, IGF-1-mediated CH chondrocytes proliferation mainly depended on the mitogen-activated protein kinase (MAPK)–ERK pathway.Conclusions: IGF-1 promotes human TMJ cartilage overgrowth in the developing process of CH by enhancing chondrocytes proliferation via MAPK–ERK pathway.

Osteoarthritis year 2011 in review: clinical - Corrected Proof

T.E. McAlindon, J.B. Driban, G.H. Lo — 2012-01-30

Summary: The purpose of this narrative year in review of clinical studies was to highlight a few publications related to obesity and weight loss, physical activity, and synovitis as well as disease modifying interventions that were published between September 2010 and September 2011. This year clinical research highlighted the extent to which obesity and osteoarthritis (OA) are impacting quality of life among adults in the United States and that reducing excessive body weight or becoming more physically active may be beneficial. In addition to weight loss and physical activity and synovitis, research over the past year has highlighted the diverse methods being pursued for structural modification interventions. In addition to chondroitin sulfate there were interesting preliminary findings that meniscal implants and joint distractions may modify OA progression.

Osteoarthritis year 2011 in review: genetics - Corrected Proof

I. Meulenbelt — 2012-01-27

Summary: In the last decades, many researchers aimed to identify causal genetic variants by means of candidate gene analyses, genome wide linkage and association studies to elucidate underlying mechanisms of osteoarthritis (OA). Although several consistent genetic variants were identified the successes are limited. This review has a focus on studies published until mid 2011 and on data presented at the Osteoarthritis Research Society International 2011 (OARSI) in San Diego and that aim to elucidate the primary molecular and cellular events commencing OA onset in humans by applying genetic study designs.

Osteoarthritis year 2011 in review: biochemical markers of osteoarthritis: an overview of research and initiatives - Corrected Proof

Y. Henrotin — 2012-01-27

Summary: The “year in review” session is a key moment of the Osteoarthritis Research Society International (OARSI) Congress. This is a unique opportunity for opinion leaders to summarize and comment the recent advances in one particular field of osteoarthritis research. This review is a summary of selected studies related to soluble biomarkers published between September 1st, 2010 and August 30th, 2011 and identified by a pubmed search using the terms “biomarkers” and “osteoarthritis”. In addition, I have selected some works presented during the 2011 OARSI Congress. This year was dominated by the publication of a consensus paper on the qualification of osteoarthritis (OA) biomarkers by the OARSI/Food Drug Administration (FDA) Osteoarthritis Biomarkers Working Group, and of proteomes of chondrocyte vesicles, urine and serum.

Reply to “Human genetic studies on osteoarthritis from clinicians’ viewpoints” - Corrected Proof

2012-01-25

Akune and Kawaguchi in an editorial comment to the paper by Kerkhof et al. raise the question whether conventional osteoarthritis (OA) genetic studies are worth the investment. The authors have misunderstood the scope and the conclusions of our paper by assuming they were limited to genetic OA research only. On the contrary, problems of disease definition affect classical observational epidemiological, biomarker or clinical trial studies and genetic studies are among the few to deal with the heterogeneity in the OA definitions.

Osteoarthritis year 2011 in review: imaging in OA – a radiologists’ perspective - Corrected Proof

D. Hayashi, F.W. Roemer, A. Guermazi — 2012-01-25

Summary: With major technological advances and application of magnetic resonance imaging (MRI) to large longitudinal osteoarthritis (OA) studies the role of imaging has become increasingly important for OA research over the last years. Currently, radiography, MRI and ultrasound are the most established imaging tools applied in a research setting. MRI assessment of OA features can be morphologic, compositional and can be applied in non-loaded and loaded conditions. Morphologic assessment includes semiquantitative and quantitative analyses. Novel semiquantitative scoring methods for knee, hip and hand OA using MRI were introduced. A series of key reports were published this year, reviewing the importance of radiography and MRI as a research tool. Although radiography is insensitive for the detection of OA-related structural pathology when compared to MRI, it still has been widely used for subject inclusion in observational and interventional studies due also to a straight forward disease definition that was established more than 50years ago. In an attempt to generate an MRI-based definition of structural disease, a Delphi exercise was performed to develop a testable MRI definition of structural OA. This presentation reviews publications related to imaging of OA, published in English between September 2010 and October 2011, excluding animal studies or in vitro data. This is not a systematic or comprehensive review and the selection of papers included is based on the expert opinions of the presenter, from a musculoskeletal radiologist’s perspective.

Weight change in osteoarthritis - Corrected Proof

L.M. Abbate, J.M. Jordan — 2012-01-24

In this issue of the journal, we re-visit the relationship of body weight with osteoarthritis (OA) in both the knee and hip joints. Body weight deserves much attention and is important in OA because it is a potentially modifiable risk factor for knee and hip OA. Furthermore, increases in overweight and obesity have been seen worldwide over the past several decades. The studies by Aaboe et al. on weight loss in knee OA and Apold et al. on weight gain in hip OA in this issue provide valuable insight into the relationship of weight change and OA.

Osteoarthritis year in review: rehabilitation and outcomes - Corrected Proof

A.M. Davis — 2012-01-24

Summary: Purpose: This review highlights seminal publications of rehabilitation interventions and outcomes in osteoarthritis (OA) of the hip or knee.Methods: Medline, CINAHL, and Embase databases from September 2010 through August 2011 were searched using the key words ‘osteoarthritis’, rehabilitation, physical therapy, exercise, and outcome(s), limited to human and English. Rehabilitation intervention studies were included if they were randomized trials (RCT), systematic reviews or meta-analyses. Studies of surgical interventions were excluded unless they included evaluation of a rehabilitation intervention. Outcome studies were included if they contributed methodologically to advancing outcome measurement. Reviews of measurement properties of outcomes were excluded. Eight publications were selected and reviewed that relate to interventions evaluating manual therapy in hip or knee OA, tele-rehabilitation and performance and participation measures as outcomes.Results: Interventions: One systematic review of hip and knee OA, one meta-analysis of knee OA provide limited support for the benefit of manual therapy with exercise for improving pain and function to a lesser extent in the short-term (3months). Study quality overall was low.One high quality RCT in knee replacement of usual outpatient physiotherapy vs internet-based tele-rehabilitation based on a non-inferiority analysis demonstrated comparable outcomes on Western Ontario McMaster Universities’ Osteoarthritis questionnaire (WOMAC) pain and function and performance measures.Outcomes: Three studies demonstrated that observed performance measures such as timed walk tests and stair-climbing and timed-up-and-go measure concepts differ from self-report of difficulty with physical function. Additionally, two studies showed differential times of recovery following total knee replacement (TKR).Two studies evaluated participation. One demonstrated the conceptual distinction of activity limitations and participation and a second re-analyzed trial data from knee OA studies. In one study, there were larger effects in combined activity/participation than for activity alone for arthroscopic lavage compared to intraarticular steroid and, in a second study, the effect was larger for activity with an advanced pharmacy intervention whereas the physiotherapy intervention demonstrated a larger effect for activity/participation.Conclusions: Interventions of manual therapy for hip and knee OA provided limited evidence of effectiveness. These studies are of limited quality due to lack of blinding and disclosure of co-intervention. Tele-rehabilitation may be a viable option to improve access to rehabilitation post joint replacement for those in rural and remote areas.Data continue to support the need to include performance measures as well as patient-reported outcomes in evaluating outcomes in OA. Additionally, measures of participation should be considered as core outcomes.

Coexistence of fibrotic and chondrogenic process in the capsule of idiopathic frozen shoulders - Corrected Proof

2012-01-16

Summary: Objective: To analyze changes in the capsule from idiopathic frozen shoulders and clarify their etiology.Materials and methods: Samples (the rotator interval capsule, middle glenohumeral ligament (MGHL), and inferior glenohumeral ligament (IGHL)) were collected from 12 idiopathic frozen shoulders with severe stiffness and 18 shoulders with rotator cuff tears as a control. The number of cells was counted and the tissue elasticity of the samples was calculated by scanning acoustic microscopy (SAM). The amount of glycosaminoglycan content was assessed by alcian blue staining. Gene and protein expressions related to fibrosis, inflammation, and chondrogenesis were analyzed by quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). Furthermore, the total genes of the two groups were compared by DNA microarray analysis.Results: The number of cells was significantly higher and the capsular tissue was significantly stiffer in idiopathic frozen shoulders compared with shoulders with rotator cuff tears. Staining intensity of alcian blue was significantly stronger in idiopathic frozen shoulders. Gene expressions related to fibrosis, inflammation, and chondrogenesis were significantly higher in idiopathic frozen shoulders compared with shoulders with rotator cuff tears assessed by both qPCR and DNA microarray analysis.Conclusion: In addition to fibrosis and inflammation, which used to be considered the main pathology of frozen shoulders, chondrogenesis is likely to have a critical role in pathogenesis of idiopathic frozen shoulders.

In end stage osteoarthritis, cartilage tissue pentosidine levels are inversely related to parameters of cartilage damage - Corrected Proof

2012-01-13

Summary: Objectives: Age is the most prominent predisposition for development of osteoarthritis (OA). Age-related changes of articular cartilage are likely to play a role. Advanced glycation endproducts (AGEs) accumulate in cartilage matrix with increasing age and adversely affect the biomechanical properties of the cartilage matrix and influence chondrocyte activity. In clinical studies AGEing of cartilage and its relation to actual cartilage damage can only be measured by surrogate markers (e.g., serum, skin or urine AGE levels and imaging or biochemical markers of cartilage damage). In this study actual cartilage AGE levels were directly related to actual cartilage damage by use of cartilage obtained at joint replacement surgery.Methods: Cartilage and urine samples were obtained from 69 patients undergoing total knee replacement. Samples were analyzed for pentosidine as marker of AGE. Cartilage damage was evaluated macroscopically, histologically, and biochemically.Results: Cartilage and urine pentosidine both increased with increasing age. The higher the macroscopic, histological, and biochemical cartilage damage the lower the cartilage pentosidine levels were. In multiple regression analysis age is not found to be a confounder.Conclusion: There is an inverse relation between cartilage AGEs and actual cartilage damage in end-stage OA. This is likely due to ongoing (ineffective) increased turnover of cartilage matrix proteins even in end stage disease.

Chondrocyte hypertrophy and osteoarthritis: role in initiation and progression of cartilage degeneration? - Corrected Proof

P.M. van der Kraan, W.B. van den Berg — 2012-01-09

Summary: Objective: To review the literature on the role and regulation of chondrocyte terminal differentiation (hypertrophy-like changes) in osteoarthritis (OA) and to integrate this in a conceptual model of primary OA development.Methods: Papers investigating chondrocyte terminal differentiation in human OA cartilage and experimental models of OA were recapitulated and discussed. Focus has been on the occurrence of hypertrophy-like changes in chondrocytes and the factors described to play a role in regulation of chondrocyte hypertrophy-like changes in OA.Results: Chondrocyte hypertrophy-like changes are reported in both human OA and experimental OA models by most investigators. These changes play a crucial part in the OA disease process by protease-mediated cartilage degradation. We propose that altered chondrocyte behavior and concomitant cartilage degradation result in a disease-amplifying loop, leading to a mixture of disease stages and cellular responses within an OA joint.Conclusion: Chondrocyte hypertrophy-like changes play a role in early and late stage OA. Since not all cells in an OA joint are synchronized, inhibition of hypertrophy-like changes might be a therapeutic target to slow down further OA progression.

Response to letter by HJM Kerkhof on “Human genetic studies on osteoarthritis from clinicians’ viewpoints” - Corrected Proof

T. Akune, H. Kawaguchi — 2012-01-09

We greatly appreciate the in-depth discussion by Dr. Kerkhof et al. on our editorial. We also thank the authors for providing us a chance to make the points clearer so that readers of the editorial avoid misunderstanding our true intention. Our editorial referred specifically to conventional low-quality studies and not to genetic studies in general if they have been carried out to a high standard. The question raised in our editorial is whether conventional osteoarthritis (OA) genetic studies in the past have been performed with sufficient scientific strictness. Unfortunately, there are many low-quality studies in which inadequate effort has been paid to the stringency of study design. The editorial stresses the importance of the exactness of phenotype definition, selection of appropriate controls, and adjustment for confounding factors for OA genetic studies to discover true OA susceptibility genes. In fact, inconsistent and ambiguous disease definition is a critical limitation of studies as the authors indicate in their paper. Use of controls such as patients with other diseases than OA or so-called healthy subjects without knee symptoms may yield misleading results since they are likely to be contaminated by a substantial percentage of OA subjects. Adjustment of age and other confounders of OA is important, but even a prestigious journal in the genetic field has not seemed to take much account of age-matching between OA cases and controls [Ref. , Table 1].

Osteoarthritis year 2011 in review: biology - Corrected Proof

M. Lotz — 2011-12-26

Summary: This review is focused on advances in understanding the biology of joint homeostasis and osteoarthritis (OA) pathogenesis mechanisms that have led to proof of concept studies on new therapeutic approaches. The three selected topics include angiogenesis in joint tissues, biomechanics and joint lubrication and mitochondrial dysfunction. This new information represents progress in the integration of mechanisms that control multiple aspects of OA pathophysiology.

WITHDRAWN: Assessment of clinical outcomes 10–20 years after autologous chondrocyte implantation - Corrected Proof

H. Vasiliadis, G. Salanti, A. Georgoulis, A. Lindahl, L. Peterson — 2010-05-06

This article has been withdrawn at the request of the Editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

WITHDRAWN: Characteristic markers of the WNT signalling pathway are differentially expressed in osteoarthritic cartilage - Corrected Proof

2010-04-30

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

REMOVED: Generation of cartilage microtissues by hanging drops: effect of different culture conditions - Corrected Proof

I. Martinez — 2007-04-28

This article has been removed, consistent with Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The Publisher apologizes for any inconvenience this may cause.