| Objectives: Osteoarthritis (OA) is a common joint disease characterized by cartilage loss and formed osteophyte. With the further investigation of the pathophysiology of OA,it was found that OA could be divided into different phenotypes according to different pathogenesis. With the increasing prevalence of obesity in the world,metabolic OA is a hot research topic. Previous studies have shown that the mechanism of metabolic inflammation in OA may be involved in the process of inflammation (cytokines and adipokines), oxidative stress, sex hormones in the fat deposition or the related tissue. Our study aims to examine the roles of systemic and local fat as well as inflammatory and metabolic mechanisms in the development and progression of symptoms and structural changes in OA.Methods: Our study is based on two databases. The first one is Anhui Osteoarthritis Database. We consecutively enrolled 205 O A patients who fulfilled the American College of Rheumatology criteria for the classification of clincial knee OA. The general informations such as age,sex,height and weight were recorded by questionnaires. Knee symptoms were assessed by The The Western Ontario and McMaster Universities Arthritis Index (WOMAC). The Kellgren-Lawrence (K-L) grade and osteophyte scores were measured by radiographic plain film. Magnetic resonance imaging (MRI) of symptomatic knee was performed with a 3.0T whole-body magnetic resonance unit.Cartilage defects, Bone marrow lesions (BMLs), cartilage volume, and Infrapatellar fat pad (IPFP) volume and signal intensity (SI) alterations were assessed on the MRI by OsiriX software. Body compositions were assessed by dual x-ray absorptiometry(DEXA). Serum levels of leptin, adiponectin,resistin,IL-17, IL-18 and MMP-3, 10, 13 were measured using ELISA. According to different data types, different statistical models were used for statistical analysis. These models were used to analyse the relationship between different body compositions,adipokines and cytokines and OA symptoms and structural changes,and the relationship between adipokines and cytokines and IPFP volume and SI alterations. The second database is Osteoarthritis Initiative Study,which is open for investigators all over the world. Case knees (n=355) were defined by iROA on the knee radiographs at any assessment after baseline (BL) but prior to the 48-month visit. They were matched one-to-one by gender, age (± 5 years) and radiographicstatus with a control knee. Control knees did not develop incident ROA from BL to 48 months. MR images were assessed at BL, P0 (visit when ROA was found on radiograph),1 year prior to PO (P-1). We used a novel method to measure IPFP signal intensity alterations quantitatively. Conditional logistic regression accounting for the correlation of knees in an individual was applied to assess risk of ROA in regard to signal intensity alteration before and after adjustment for covariates measured at baseline. Models were run at three time points.Results: First part, we found that BMI and lean mass were positively associated with bone marrow lesions, and weight, BMI and fat mass were positively associated with osteophyte; but lean mass was not associated with osteophyte. Furthermore, while BMI was positively correlated with the severity of OA and fat mass was positively associated with severity of OA, lean mass was negatively associated with severity of OA. Second part, our results showed that 1) serum leptin level was negatively correlated with OA symptoms of stiffness; 2) serum adiponectin levels were negatively correlated with cartilage defects in knee joints; 3) serum resistin levels were positively correlated with cartilage defects and bone marrow lesions; 4) serum levels of IL-17 were positively correlated with cartilage defects and bone marrow lesions in the highest level group of high sensitivity C reactive protein (hs-CRP); 5) serum levels of IL-18 were positively and consistently correlated with medial tibial and femoral cartilage defects and lateral tibial femoral bone marrow lesions, total cartilage volume, degradation products of cartilage,and joint symptom assessed by WOMAC scores. Third part, we reported that high serum levels of IL-17 were associated with a decrease in IPFP volume and an increase in signal intensity alterations. Serum levels of adiponectin were positively associated with IPFP volume and negatively associated with signal intensity alterations of IPFP. Serum levels of resistin were positively associated with signal intensity alteration of IPFP. Fourth part,We found that almost all the baseline IPFP measurements were correlated with incidence of Radiographic OA (ROA) in 4 years. All IPFP measurements were correlated with the incidence of ROA at P-0 (the visit when iROA was found on radiograph) and P-1 (1 year prior to P-0).Conclusions: In summary, body fat mass and lean mass may play different roles in the progression of OA, serum adipokines and cytokines may mediate the link between metabolic inflammation and symptoms and structural changes in knee OA, and IPFP may play an important predictive role in the incidence of ROA. |
