Osteoarthritis

Das, Siddharth Kumar; Farooqi, Abid

doi:10.1016/j.berh.2008.07.002

Cited by 104 publications

(83 citation statements)

References 83 publications

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“…This is coincident with the previous conclusion that obesity and gender are major risk factors for knee OA. 17 Our results showed that age was an independent risk factor in the overweight group. In this group, the frequency distribution of two genotypes (AA at rs12706832 and TT at rs2071045) was different.…”

Section: Discussionmentioning

confidence: 48%

Association of the leptin gene with knee osteoarthritis susceptibility in a Han Chinese population: a case–control study

et al. 2010

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Previous studies have suggested that leptin works as a key regulator in the pathogenesis of osteoarthritis (OA), and genetic factors modulate OA. This study assessed the contribution of leptin gene (LEP) polymorphism(s) to knee OA among Han Chinese. Three tag single-nucleotide polymorphisms (SNPs) covering all those LEP SNPs of which the minor allele frequencies were over 10% were selected. Study subjects (697 patients and 699 controls) were divided into four groups (underweight, normal weight, overweight and obese) by body mass index (BMI). Allele and genotype frequencies in the three tag SNPs were significantly different in the normal weight and overweight groups. In the normal weight, overweight and obese groups, BMI (P¼4.3Â10 À5 , 0.012 and 0.009, respectively) and gender (P¼3.5Â10 À22 , 5.1Â10 À23 and 2.1Â10 À8 , respectively) were effective factors. Age was an independent effective factor in the overweight group (P¼0.009). Haplotypes were associated with OA in the normal weight group (CAT, P¼0.015) and the overweight group (AGC, P¼0.015). Our results suggest an association between LEP and knee OA in the normal weight and overweight groups among Han Chinese. Keywords: case-control association study; leptin; osteoarthritis; tag SNPs INTRODUCTION Knee osteoarthritis (OA) usually causes considerable pain and frequent instability, consequently resulting in physical disability. 1 Among Chinese of over 60 years of age, prevalence of symptomatic knee OA is 19.4%. 2 For knee OA, obesity is a major risk factor, and genetic factors modulate obesity and OA. 3 Classic twin studies have shown that the genetic influence is between 39 and 65% in radiographic OA of the hand and knee in women. 4 Previous studies found associations of knee OA with ASPN, GDF5 and DVWA, and metaanalysis showed global association in GDF5, whereas ASPN and DVWA have ethnic differences. [5][6][7] Leptin is a 16-kDa non-glycosylated peptide hormone, mainly produced by adipocytes. 8 Leptin protein level is much higher in OA cartilage than in normal cartilage. 9 It participated in the pathogenesis of OA by affecting chondrocyte metabolism. 10,11 A high level of leptin expression increases nitric oxide, matrix metaloprotease-9 and matrix metaloprotease-13 expression, affects chondrocyte function and finally results in OA. 11,12 However, so far, few studies have been conducted on the possible existence of association between leptin gene (LEP) polymorphisms and OA susceptibility.

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Section: Discussionmentioning

confidence: 48%

Association of the leptin gene with knee osteoarthritis susceptibility in a Han Chinese population: a case–control study

et al. 2010

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“…1) OA is characterized by progressive degradation of articular cartilage and chondrocytes apoptosis and death. 2) Chondrocytes apoptosis has been identiˆed as a vital reason for cell loss and is now considered as an important factor contributing to degradation of extracellular matrix (ECM) in OA cartilage. 3) Many researches have also demonstrated that enzymatic cleavage by matrix metalloproteinases (MMPs) together with cytokines plays critical roles in the initiation and progression of cartilage destruction.…”

Section: Introductionmentioning

confidence: 99%

Protective Effect of Sinomenine on Cartilage Degradation and Chondrocytes Apoptosis

Deng

et al. 2010

YAKUGAKU ZASSHI

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Sinomenine (SIN), an alkaloid extracted from the stem of the Chinese medicinal plant sinomenium acutum, has been used for treating rheumatoid arthritis. But little is known whether SIN has a protective eŠect on osteoarthritis (OA). In this study, we investigated the protective eŠect of SIN on IL-1b-induced proteoglycan degradation and apoptosis in rabbit articular cartilage and chondrocytes. Treatment with 10 ng/ml IL-1b increased the level of glycosaminoglycan (GAG) released into the culture media, and up-regulated the activity and mRNA expression of matrix metalloproteinase 13 (MMP-13) and down-regulated the activity and mRNA expression of tissue inhibitor of metalloproteinase 1 (TIMP-1) in cartilage explants, as conˆrmed by the methods of GAG quantitation, MMP-13/TIMP-1 enzyme-linked immunosorbent assay (ELISA) and real-time quantitative RT-PCR. Treatment with 10 ng/ml IL-1b resulted in marked apoptosis in chondrocytes, as demonstrated by decreased cell viability, occurrence of DNA laddering and increased caspase-3 activity and annexin V binding of phosphatidylserine. However, simultaneous treatment with SIN (10, 50 or 250 mM) inhibited the GAG release and the activity and mRNA expression of MMP-13, and enhanced the activity and mRNA expression of TIMP-1 in a dose-dependent manner in cartilage explants. Furthermore, DNA fragment, caspase-3 activity and apoptosis rate were down-regulated, and cell viability was up-regulated dose-dependently in chondrocytes. Thus, SIN has the protective capacity to antagonize cartilage degradation and chondrocyte apoptosis, which suggest that SIN may act as an agent for pharmacological intervention in the progress of OA.

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“…It has been argued that OA is not the result of a single genetic anomaly but rather it is under the influence of multiple genes and environmental factors. Genetic analyses have shown that ADAM12, BMP2, CD36, COX2, NCOR2 genes are related to OA and associations of loci on the 2nd, 4th, 6th, 7th, 11th, 16th chromosomes and X chro- mosome with OA have been demonstrated (21). Relationships between different HLA alleles and OA or OA variants are also known.…”

Section: Discussionmentioning

confidence: 99%

Relationship between Primary Nodal Generalized Osteoarthritis with Tissue Antigens HLA-A and HLA-B in the Western Black Sea Region of Turkey

et al. 2011

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Objective To investigate the relationship between patients diagnosed with nodal generalized osteoarthritis (NGOA) and tissue antigens HLA-A and HLA-B in the Western Black Sea Region of Turkey. Patients and Methods Forty-six patients with NGOA (64.74±8.46) and 60 controls (62.32±6.8) were included in the study. Inclusion criteria were: (i) stage 2 and higher OA of the hand and knee based on the Kellgren-Lawrence classification, and (ii) stage 2 and higher lumbar disc degeneration according to Lawrence classification. Family histories were taken from patients. HLA-A and HLA-B were typed by PCR using sequence specific primer.

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Osteoarthritis

Cited by 104 publications

References 83 publications

Association of the leptin gene with knee osteoarthritis susceptibility in a Han Chinese population: a case–control study

Association of the leptin gene with knee osteoarthritis susceptibility in a Han Chinese population: a case–control study

Protective Effect of Sinomenine on Cartilage Degradation and Chondrocytes Apoptosis

Relationship between Primary Nodal Generalized Osteoarthritis with Tissue Antigens HLA-A and HLA-B in the Western Black Sea Region of Turkey

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