Article

Serum transforming growth factor-beta 1 is not a robust biomarker of incident and progressive radiographic osteoarthritis at the hip and knee: The Johnston County Osteoarthritis Project

Department of Medicine, Thurston Arthritis Research Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Osteoarthritis and Cartilage (Impact Factor: 4.17). 02/2010; 18(6):825-9. DOI: 10.1016/j.joca.2010.02.013
Source: PubMed

ABSTRACT

To test whether serum transforming growth factor-beta 1 (TGF-beta1) predicts incident and progressive hip or knee radiographic OA (rOA).
Serum TGF-beta1 was measured for 330 participants aged 45 years and older in the Johnston County Osteoarthritis Project, with paired longitudinal films available for 618 hips and 658 knees. Incident and progressive rOA were defined using Kellgren-Lawrence (K-L) grade as well as osteophyte (OST) and joint space narrowing (JSN) scores. Natural logarithm transformation was used to produce near-normal distributions for continuous TGF-beta1 (lnTGF-beta1). Separate multivariable Weibull regression models were used to provide hazard ratios (HRs) for a 1-unit increase lnTGF-beta1 with each rOA outcome, accounting for variable follow-up times and clustering by individual, adjusted for age, race, gender, and body mass index (BMI). Interaction terms were considered statistically significant at P<0.10.
The mean (+/-SD) age of the sample was 61.9+/-9.7 years, the mean BMI was 30.3+/-6.9 kg/m(2), with 60.6% women and 42.4% AA. The mean (+/-SD) TGF-beta1 was 17.8+/-6.1 ng/ml; follow-up time was 6.1+/-1.3 years. There were no significant interactions by race or gender. HRs showed no significant relationship between lnTGF-beta1 and incident or progressive rOA, OST, or JSN, at the knee or the hip.
Levels of TGF-beta1 do not predict incident or progressive rOA, OST, or JSN at the hip or knee in this longitudinal, population-based study, making it unlikely that TGF-beta1 will be a robust biomarker for rOA in future studies.

Download full-text

Full-text

Available from: Yvonne M Golightly, Jul 03, 2014
    • "Three other markers (circulating levels of aggrecan, cellular inhibitor of apoptosis protein (cIAP), and serum level of keratan sulfate (KS)) were not associated with incidence[12,13]and progression risk of knee OA[28]. Moreover, levels of transforming growth factor-beta 1, a multifunctional growth factor with a role in cartilage matrix metabolism, did not predict incident or progressive radiographic OA or JSN at the hip or knee in Johnston County Osteoarthritis Project, a community-based longitudinal study[14]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The identification of early biochemical predictors of osteoarthritis (OA) has been the focus of much research over the past few years. However, it still is unclear whether current biochemical markers can be used in prognostic risk assessment of OA. The aim of this systematic review is to evaluate the possible prognostic application of blood and urinary biochemical markers of knee and hip OA. Abstract and full text selection was done by two independent reviewers. A total of 25 relevant publications including 37 biochemical markers of bone and cartilage turnover and inflammation associated with some aspects of OA were reviewed. Most of those biomarkers were studied only once or twice. Due to heterogeneity of both OA-phenotype and determinant among the publications, meta-analysis of the studied biochemical markers was not possible. There was strong evidence for urinary C-terminal telopeptide of collagen type II (uCTX-II) as a prognostic marker for knee OA progression and serum cartilage oligomeric protein (COMP) level as prognostic marker for incidence of knee and hip OA. Evidence for prognostic value of C-reactive protein is still inconclusive. International standardization of future investigations should be pursued to obtain more high-quality, homogenous data on the full spectrum of biochemical OA markers. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    No preview · Article · Apr 2015 · Maturitas
  • Source
    • "Lastly, in the largest study of serum TGF-β to date, Nelson and colleagues [70] reported that this marker was higher in women than men in the JoCo OA and that the associations between this marker and prevalent radiographic knee and hip OA, osteophytes, and joint space narrowing were similar in men and women. A single measure of this marker was unable to predict incidence or progression of radiographic knee or hip OA, osteophytes, or joint space narrowing in either men or women [71]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Sex differences in the prevalence, incidence, and severity of osteoarthritis (OA) have long been known. Some differences in the evaluation of this issue across studies may be related to differences in study design, sampling, study size, study populations, targeted joint sites, and definitions of OA. This report highlights recent studies of sex differences in individual joint components imaged by magnetic resonance imaging and in systemic biomarkers of joint metabolism. Particularly important are those studies that examine this issue in young unaffected adults and children before the development of disease. Despite some variation across studies, women appear for the most part to have a thinner and more reduced volume of cartilage in the knee than men, and this may occur from early childhood. It is not clear whether women have a more accelerated rate of cartilage volume loss than men. Few data exist on sex differences in systemic biomarkers of joint metabolism. In these studies, it is critically important to characterize the total body burden of OA and the presence of comorbid conditions likely to influence a given biomarker. Lastly, future research should dovetail studies of sex differences in imaging and biochemical biomarkers with genetics to maximize insight into the mechanisms behind observed sex differences.
    Full-text · Article · Jul 2010 · Arthritis research & therapy
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: As osteoarthritis (OA) is a highly heterogeneous disease in terms of progression, establishment of prognostic biomarkers would be highly beneficial for treatment. The present study was performed to identify novel biomarkers capable of predicting the progression of knee OA. A total of 69 plasma samples (OA patients undergoing radiographic progression, n = 25; nonprogression, n = 33; healthy donors, n = 11) were analyzed by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS), and ion peaks of interest were identified by liquid chromatography and matrix-assisted laser desorption/ionization (MALDI)-TOF MS. The identities of these proteins were further validated by immunoprecipitation combined with SELDI-TOF MS analysis. SELDI-TOF MS analysis indicated that the intensities of 3 ion peaks differed significantly between progressors and nonprogressors. Subsequent analyses indicated that these peaks corresponded to apolipoprotein C-I, C-III, and an N-terminal truncated form of transthyretin, respectively. The identities of these proteins were confirmed by the loss of ion peaks in SELDI-TOF MS spectra by immunoprecipitation using specific antibodies for the respective proteins. Three potential biomarkers were identified whose serum levels differed significantly between OA progressors and nonprogressors. These biomarkers are expected to be prognostic biomarkers for knee OA and to facilitate the development of novel disease-modifying treatments for OA.
    Full-text · Article · Jul 2013 · Biomarker insights
Show more