Background During osteoarthritis (OA), articular cartilage degradation is essentially due to the increase of the expression of pro-catabolic factors, such as nerve growth factor (NGF), interleukin-17 (IL-17) that activate the local synthesis of metalloproteases (mainly MMP-13) and aggrecanase (mainly ADAMTS-5) leading to the breakdown of type II collagen and proteoglycans with microscopic and macroscopic damage. In obesity, adipose visceral tissue over-produces pro-flogistic and pro-catabolic mediators such as tumour necrosis factor (TNF-α), IL-1β, IL-17, NGF. In addition, the adipocytes produce specific adipokines and leptin has been involved in the pathophysiology of OA. Leptin has been reported to selectively promote the synthesis of pro-flogistic mediators and proteases in OA chondrocytes and thus representing a possible pathogenic link between obesity and OA.
Objectives To evaluate 1) the histological differences of the articular cartilage between obese and normal- weight patients with OA, 2) the differences in expression of MMP-13, ADAMTS-5, NGF, IL-17, IL-10 and leptin in the articular cartilage of obese and normal-weight OA patients, 3) the correlation between the expression of these molecules and body mass index (BMI) and cartilage damage.
Methods Articular cartilage of the tibial plateau of 19 obese patients (13 women, 6 men; BMI between 31-37; age 41-84 years) and 10 normal-weight patients (6 women, 4 men; BMI between 21-23; age 28-73 years) undergoing surgery knee replacement for OA. Classical histology (toluidine blue stain) for the assessment of OARSI score cartilage damage, immunohistochemical staining for the semi-quantitative evaluation of the cellular expression and RTQ-PCR for the quantification of gene expression of the different molecules were carried out. Statistical analysis was performed using Spearman rank correlation or U-Mann Whitney tests.
Results We found a statistically significant linear correlation between OARSI cartilage score and BMI (r=0.64, p=0.0002). The immunohistochemical findings showed a statistically significant linear correlation between cellular expression of leptin and OARSI score (r=0.79, p=0.0001) or BMI (r=0.48, p=0.0001). Likewise, NGF expression correlated with OARSI score (r=0.82, p<0.0001) or BMI (r=0.76, p<0.0001), ADAMTS-5 with OARSI score (r=0.8734, p≤0.0001) or BMI (r=0.55, p=0.001) and MMP-13 with OARSI score (r=0.80, p=0.0001) or BMI (r=0.69, p=0.0001), respectively. No difference in the cellular expression of IL- 17 between OA groups was detected. Concerning IL- 10, we found an inverse linear trend between cellular expression and OARSI score (r=-0.37, p=0.1) and statistically significant inverse linear correlation with BMI (r=-0.823, p<0.000). These findings were confirmed by RTQ-PCR analysis.
Conclusions This study provides further evidence that obesity has not only a mechanical impact on articular cartilage but has also a pro-inflammatory pattern fostering the dysregulation of the activity of chondrocytes and enabling the development of OA.
Disclosure of Interest None declared
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