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Relationship of age and body mass index to the expression of obesity and osteoarthritis-related genes in human meniscus.

ABSTRACT: Aging and obesity contribute to the initiation and progression of osteoarthritis with little information on their relation to gene expression in joint tissues, particularly the meniscus. Here, we test the hypothesis that patient age and body mass index (BMI) correlate with the expression of osteoarthritis- and obesity-related gene signatures in the meniscus.Meniscus was obtained from patients (N=68) undergoing arthroscopic partial meniscectomy. The mRNA expression of 24 osteoarthritis-related and 4 obesity-related genes in meniscus was assessed by quantitative real-time PCR. The relationship between gene expression and patient age and BMI was analyzed using Spearman's rank-order correlation. Hierarchical cluster dendrogram and heat map were generated to study inter-gene associations.Age was negatively correlated (P<0.05) with the expression of MMP-1 (r=-0.447), NF?B2 (r=-0.361), NF?BIA (r=-0.312), I?BA (r=-0.308), IL-8 (r=-0.305), ADAMTS-4 (r=-0.294), APLN (apelin) (r=-0.250) and IL-6 (r=-0.244). Similarly, BMI was negatively correlated with the expression of APLN (r=-0.328), ACAN (r=-0.268) and MMP-1 (r=-0.261). After adjusting for the correlation between age and BMI (r=0.310; P=0.008), the only independent effect of BMI on gene expression was for APLN (r=-0.272). However, age had an independent effect on the expression on ADAMTS-4 (r=-0.253), MMP-1 (r=-0.399), IL-8 (r=-0.327), COL1A1 (r=-0.287), NF?BIA (r=-0.278), NF?B2 (r=-0.312) and I?BA (r=-0.299). The gene correlation analysis identified four clusters of potentially relevant genes: transcription factors, matrix-degrading enzymes, cytokines and chemokines, and obesity genes.Age and BMI were negatively correlated with several osteoarthritis- and obesity-related genes. Although the bulk of these changes appeared to be driven by age, expression of APLN was related to BMI. Inter-gene correlation analysis implicated a common role for strongly correlated genes. Although age-related variations in gene expression appear to be more relevant than obesity-related differences for the role of the meniscus in osteoarthritis development, further investigation into the role of APLN in meniscus and joint health is warranted.

SUBMITTER: Rai MF

PROVIDER: S-EPMC3751987 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Relationship of age and body mass index to the expression of obesity and osteoarthritis-related genes in human meniscus.

Rai M F MF Sandell L J LJ Cheverud J M JM Brophy R H RH

International journal of obesity (2005) 20130115 9

<h4>Objective</h4>Aging and obesity contribute to the initiation and progression of osteoarthritis with little information on their relation to gene expression in joint tissues, particularly the meniscus. Here, we test the hypothesis that patient age and body mass index (BMI) correlate with the expression of osteoarthritis- and obesity-related gene signatures in the meniscus.<h4>Design</h4>Meniscus was obtained from patients (N=68) undergoing arthroscopic partial meniscectomy. The mRNA expressio ...[more]

PMID: 23318714

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Project description:Higher body mass index (BMI) increases the risk of meniscus injury and knee osteoarthritis (OA). However, it is unknown if and how obesity affects meniscus biology. We analyzed transcriptome-wide gene expression profiles of injured human menisci to test the hypothesis that meniscal gene expression signatures relate to patient BMI.Meniscus samples were obtained from patients undergoing arthroscopic partial meniscectomy. Transcriptome-wide analysis of gene expression followed by validation of selected transcripts by QuantiGene Plex assay was performed. Correlations of gene expression with BMI and relative fold changes (?1.5-fold) in 3 BMI categories (lean [BMI 18.5-24.9 kg/m(2) ], overweight [BMI 25.0-29.9 kg/m(2) ], and obese [BMI >30.0 kg/m(2) ]) were analyzed, and integrated functional classifications were probed computationally.The obese versus overweight comparison resulted in the largest set of differences (565 transcripts) followed by obese versus lean (280 transcripts) and overweight versus lean (125 transcripts). Biologic reproducibility was confirmed by cluster analysis of expressed transcripts. Differentially regulated transcripts represented important functional classifications. Transcripts associated with oxygen transport, calcium ion binding, and cell homeostasis were elevated with BMI, while those related to extracellular matrix deposition, cell migration, and glucosamine metabolic processes were repressed. While these functional classifications may play key roles in cartilage/meniscus homeostasis, failure of extracellular matrix deposition and increase in calcium ion binding likely contribute to OA development following meniscal injury.Our results indicate greater differences in gene expression between obese and overweight groups than between overweight and lean groups. This may indicate that there is a weight threshold at which injured meniscus responds severely to increased BMI. BMI-related changes in gene expression present a plausible explanation for the role of meniscal injury in OA development among obese patients.

Project description:BackgroundIncrease body mass index (BMI) is often accompanied by metabolic diseases such as diabetes, which will increase the uncertainty of total knee arthroplasty (TKA) efficacy and the risk of postoperative complications. The present study was to study the relationship between increase BMI and clinical efficacy of knee arthroplasty in patients with knee osteoarthritis.MethodsA total of 97 patients (36 males and 61 females) with knee osteoarthritis (KOA) who underwent TKA surgery were selected. According to the preoperative body mass index (BMI), the patients were divided into a normal group (n=42), overweight group (n=35), and obese group (n=20). All patients received TKA after admission. Seven days after surgery, the American Knee Society (AKS) and the Hospital for Special Surgery (HSS) scales were used to evaluate the recovery of knee function. The recovery was poor if the scores of AKS and HSS were less than 70.ResultsSeven days after TKA, the scores of AKS and HSS in different BMI groups were significantly different, and decreased with the increase of BMI (P<0.05). Age, increased BMI, diabetes, preoperative range of motion (ROM), intraoperative blood loss, postoperative C-reactive protein (CRP), postoperative posterior slope angle (PSA), postoperative infection, and postoperative deep vein thrombosis (DVT) of lower extremities were related to AKS score <70 (P<0.05). Diabetes, preoperative ROM, intraoperative blood loss, postoperative CRP, postoperative PSA, and postoperative infection were related to HSS score <70 (P<0.05). Increased BMI, diabetes, postoperative CRP, postoperative infection, and postoperative DVT were independent risk factors for AKS score <70 (HR =3.458, 1.152, 2.960, 1.023, 3.589, P<0.05). Increased BMI, diabetes, postoperative CRP, and postoperative infection were independent risk factors for HSS score <70 (HR =6.891, 1.263, 1.967, 1.235, P<1.235). The area under the curve (AUC) (95% CI) of BMI in diagnosing AKS <70 was 0.740 (0.641-0.839). The AUC (95% CI) of BMI in diagnosing HSS <70 was 0.809 (0.723-0.894).ConclusionsThe increase of BMI is an independent risk factor for the poor recovery of knee function after TKA in patients with KOA.

Project description:BackgroundMuscle quality (i.e., the expression of muscle function per unit of muscle mass) has been proposed as a clinically-relevant measure to detect individuals at risk of functional incapacity. Individuals with obesity might be at an increased risk of having poor muscle quality. Thus, we aimed to analyze the prevalence of poor muscle quality in obese individuals, to determine associated variables, and to provide normative values for this population.Methods203 individuals with obesity (103 women, age: 18-75 years, body mass index (BMI): 35-64 kg·m- 2) participated in this cross-sectional study. Their muscle strength (handgrip dynamometry), muscle power (sit-to-stand test) and muscle mass (bioelectrical impedance analysis) were measured, and muscle quality (strength/power to muscle mass ratio) was compared with reference values obtained in young healthy individuals. Muscle quality was individually categorized as normal, low or poor based on specific muscle strength and power (i.e., strength and power per unit of muscle mass, respectively). Sex and age-specific normative values of specific muscle strength and power were computed for the whole cohort.ResultsAge and being a woman were inversely associated with specific muscle strength, with age being also inversely associated with specific muscle power. A small proportion of participants (6%) presented with an impaired (i.e., low/poor) specific muscle power while most of them (96%) had impaired specific muscle strength. Eventually, 84% of the participants were deemed to have poor muscle quality. Being a woman (odds ratio [OR]: 18.09, 95% confidence intervals [CI]: 4.07-80.38), age (OR: 1.06, 95%CI: 1.03-1.10) and BMI (OR: 1.22, 95%CI: 1.07-1.38) were independently associated with a higher risk of poor muscle quality in adjusted analyses.ConclusionsThese findings show a high prevalence of poor muscle quality among individuals with obesity, with age, sex and BMI being independent predictors.

Project description:BackgroundThe accumulation of disparate diseases in complex multimorbidity makes prevention difficult if each disease is targeted separately. We aimed to examine obesity as a shared risk factor for common diseases, determine associations between obesity-related diseases, and examine the role of obesity in the development of complex multimorbidity (four or more comorbid diseases).MethodsWe did an observational study and used pooled prospective data from two Finnish cohort studies (the Health and Social Support Study and the Finnish Public Sector Study) comprising 114 657 adults aged 16-78 years at study entry (1998-2013). A cohort of 499 357 adults (aged 38-73 years at study entry; 2006-10) from the UK Biobank provided replication in an independent population. BMI and clinical characteristics were assessed at baseline. BMIs were categorised as obesity (≥30·0 kg/m2), overweight (25·0-29·9 kg/m2), healthy weight (18·5-24·9 kg/m2), and underweight (<18·5 kg/m2). Via linkage to national health records, participants were followed-up for death and diseases diagnosed according to the International Classification of Diseases 10th Revision (ICD-10). Hazard ratios (HRs) with 95% CIs and population attributable fractions (PAFs) for associations between BMI and multimorbidity were calculated.FindingsMean follow-up duration was 12·1 years (SD 3·8) in the Finnish cohorts and 11·8 years (1·7) in the UK Biobank cohort. Obesity was associated with 21 non-overlapping cardiometabolic, digestive, respiratory, neurological, musculoskeletal, and infectious diseases after Bonferroni multiple testing adjustment and ignoring HRs of less than 1·50. Compared with healthy weight, the confounder-adjusted HR for obesity was 2·83 (95% CI 2·74-2·93; PAF 19·9% [95% CI 19·3-20·5]) for developing at least one obesity-related disease, 5·17 (4·84-5·53; 34·4% [33·2-35·5]) for two diseases, and 12·39 (9·26-16·58; 55·2% [50·9-57·5]) for complex multimorbidity. The proportion of participants of healthy weight with complex multimorbidity by age 75 years was observed by age 55 years in participants with obesity, and degree of obesity was associated with complex multimorbidity in a dose-response relationship. Compared with obesity, the association between overweight and complex multimorbidity was more modest (HR 2·67, 95% CI 1·94-3·68; PAF 13·3% [95% CI 9·6-16·3]). The same pattern of results was observed in the UK Biobank cohort.InterpretationObesity is associated with diverse, increasing disease burdens, and might represent an important target for multimorbidity prevention that avoids the complexities of multitarget preventive regimens.FundingWellcome Trust, Medical Research Council, National Institute on Aging.

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Relationship of age and body mass index to the expression of obesity and osteoarthritis-related genes in human meniscus.

Publications

Relationship of age and body mass index to the expression of obesity and osteoarthritis-related genes in human meniscus.

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