gms | German Medical Science

Objectives: Osteoarthritis (OA) is a chronic joint disease characterized by progressive degradation of articular cartilage as well as by pathological changes in surrounding tissues. During OA pathogenesis fibrotic changes occur in infrapatellar fat pad (IFP), which might contribute to genesis of pain. In addition, recent studies have demonstrated that the glycoprotein thrombospondin-4 (TSP-4), originally detected in the extracellular matrix of cartilage and released during progressive cartilage degradation, is involved in pain development. In the present study, relationships between IFP fibrosis, TSP-4 expression in the IFP and knee joint pain were investigated.

Methods: IFP tissue and synovial fluid samples were collected from 20 patients undergoing total knee replacement surgery. Paraffin-embedded IFP sections were systematically stained with standard HE and Masson trichrome to assess fibrotic changes as well as immunohistochemically for TSP-4. The degree of fibrosis was evaluated by quantifying fibrotic areas, number of vessels and lymphocytic infiltration. In addition, TSP-4 stained areas were quantified in adjacent sections. The concentration of TSP-4 in synovial fluid samples was quantified using an commercially available ELISA. Pain levels of OA patients were assessed preoperatively using WOMAC-Score.

Results and conclusion: A clear correlation between degree of fibrosis, vascularization and lymphocytic infiltration was detected. This was independent of patient-specific parameters such as BMI, age and sex. The expression of TSP-4 could be detected in human IFP tissue at the protein level. Moreover, the degree of fibrosis correlated with TSP-4-stained areas. Regarding the degree of fibrosis and TSP-4-stained areas, four patient subgroups could be distinguished. Interestingly, a moderate TSP-4 expression could already be detected in samples with a low degree of fibrosis. There was no significant correlation between TSP-4 staining intensity in IFP and pain, however, it is striking that high TSP-4 values were never associated with low pain levels. The concentration of TSP-4 in synovial fluid ranged from 655–1,988 ng/ml (150–500% higher than in serum). There was no correlation between TSP-4 staining intensity and synovial fluid TSP-4 concentrations. A significant relationship between synovial fluid TSP-4 concentration and pain intensity was found only in female OA patients. For the first time, TSP-4 expression was demonstrated in the IFP. The correlation between TSP-4 staining intensity and degree of fibrosis and in particular the fact that increased TSP-4 intensity was observed in sections with minor fibrotic changes suggests that TSP-4 might play a role in the development of IFP fibrosis. While TSP-4 in IFP does not seem to contribute to genesis of pain, TSP-4 in synovial fluid might play an important role in this regard. The analysis of synovial fluid and serum samples in larger patient cohorts will show if TSP-4 could be used as a pain biomarker or even represent a novel analgesic target.