Expression of focal adhesion kinase, Akt/PKB, Elk-1 and p90RSK in rheumatoid arthritis tissues but not at sites of cartilage invasion

Objective

To investigate expression of the focal adhesion kinase (FAK), Akt/PKB and the transcription factors Elk-1 and p90RSK in rheumatoid arthritis (RA).

Materials and methods

Synovial tissues from eight RA synovia (FAK, Akt/PKB) or six RA synovia (Elk-1, p90RSK), one osteoarthritis (OA) synovia and two normal synovia were investigated by immunohistochemistry with antibodies recognizing the phoshorylated of the respective molecules. In addition, cultured rheumatoid arthritis synovial fibroblasts (RASF) and normal (N) synovial fibroblasts were coimplanted with human cartilage for 60 days. The invasion score was determined on H & E stained sections, and sections with strong cartilage invasion were also stained for the aforementioned molecules by immunohistochemistry utilizing the avidin–biotin detection system.

Results

In RA tissues, FAK was expressed in the lining, sublining layer and perivascular layer. Limited perivascular FAK expression was detected in two normal synovia and no staining occurred in one OA tissue. In the lining and sublining, Akt/PKB was present in all investigated RA tissue, but not in the normal synovia and only in a few cells of the OA sample. Cartilage invading RASF neither stained for FAK or for Akt/PKB. The transcription factor Elk-1 was expressed in RA tissues in both the lining and sublining layer. No staining was detected in normal synovium, and only limited Elk-1 expression in the lining layer of one OA tissue. In addition, p90RSK was also expressed in RA tissues in the lining and sublining layer; however, no staining occurred in the normal synovium. In OA tissue, staining was restricted to the lining layer. SCID mice sections with strong cartilage invasion of RASF did not stain positive for Elk-1 or for p90RSK.

Conclusions

We suggest that expression of the phosphokinases FAK, Akt/PKB and the transcription factors Elk-1 and p90RSK are associated with inflammation, but not with cartilage invasion in RA. Therefore, we assume that these molecules might not be therapeutic targets to inhibit cartilage destruction in RA.