Background Over 50% of osteoarthritis (OA) patients show synovial inflammation, even at early stages of the disease. However, if and how this synovial activation contributes to the irreversible joint pathology that characterizes OA, is not known.
Objectives To identify common pathways that may determine progression of cartilage damage and osteophyte formation in OA.
Methods From 25 patients with knee OA that entered the CHECK Cohort study (Cohort Hip and Cohort Knee) synovial biopsies were collected at baseline. CHECK is a prospective 10-year follow-up study on patients with early osteoarthritis-related complaints initiated by the Dutch Arthritis Foundation. At baseline and follow-up, radiographs were analyzed using the KIDA (Knee Image Digital Analysis) system. Progression was determined based on change of joint space width (JSW) and osteophyte size in these radiographs. Synovial samples from baseline were studied using histology and microarray (affymetrix U133-plus-2.0), and Functional Annotation Clustering (FAC) was done using DAVID.
Results To detect genes and pathways that were predictive for progression of joint damage between baseline and t=5 years, we identified patients that were marked progressors or non-progressors, either based on JSW (respectively n=13 vs n=8) or osteophyte size (respectively n=10 vs n=11) at these time points. At baseline, neither minimum JSW nor osteophyte size differed between the groups. Among the genes that were differentially expressed by osteophyte progressors were MMP1, 2, 3, 9 and -14, whereas in JSW-progressors only MMP1 was differentially expressed. In the group of JSW-progressors, macrophage markers like CD14, S100A8, S100A9, MHC class II genes, and CXCR2 were positively associated with progression. This indicates that expression of these factors may predict, or even be involved in, progression of cartilage damage in OA patients. The osteophyte-progressors also showed an increase of most of these markers, but to a far lesser extent. Using FAC we identified inflammatory response, macrophage differentiation, blood vessel formation, ossification and cell migration to be enriched in JSW-progressors. Blood vessel formation, wound healing, ossification and cell proliferation were enriched in osteophyte-progressors. Histologically, in the JSW-progressors the lining layer was thicker and the cellularity was higher in the sublining compared to non-progressors, and compared to osteophyte progressors. Both JSW-progressors and osteophyte-progressors showed increased vascularisation compared to non-progressors.
Conclusions These data suggest an active role for the synovium in OA pathology, and identifies pathways that are likely to be involved. We found evidence for a difference in underlying processes in the synovium regarding progression of cartilage damage and progression of osteophyte formation. The presence of macrophages, especially in the lining layer, appears to be associated with progression of cartilage damage, whereas synovial expression of MMPs seems to be related to progression of osteophyte formation.
Disclosure of Interest None declared
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