Differential expression of the FAK family kinases in rheumatoid arthritis and osteoarthritis synovial tissues

The focal adhesion kinase (FAK) family kinases, including FAK and proline-rich kinase 2 (Pyk)2, are the predominant mediators of integrin alpha v beta 3 signaling events that play an important role in cell adhesion, osteoclast pathology, and angiogenesis, all processes important in rheumatoid arthritis (RA). Using immunohistochemical and western blot analysis, we studied the distribution of phospho (p) FAK, pPyk2, pSrc, pPaxillin and pPL gamma. in the synovial tissue (ST) from patients with RA, osteoarthritis (OA) and normal donors (NDs) as well as in RA ST fibroblasts and peripheral blood differentiated macrophages (PB M Phi s) treated with tumor necrosis factor-alpha (TNF alpha) or interleukin-1 beta (IL1 beta). RA and OA STs showed a greater percentage of pFAK on lining cells and M Phi s compared with ND ST. RA ST fibroblasts expressed pFAK at baseline, which increased with TNF alpha or IL1 beta stimulation. Pyk2 and Src were phosphorylated more on RA versus OA and ND lining cells and MFs. pPyk2 was expressed on RA ST fibrobasts but not in MFs at baseline, however it was upregulated upon TNF alpha or IL1 beta activation in both cell types. pSrc was expressed in RA ST fibroblasts and MFs at baseline and was further increased by TNF alpha or IL1 beta stimulation. pPaxillin and pPLC. were upregulated in RA versus OA and ND lining cells and sublining M Phi s. Activation of the FAK family signaling cascade on RA and OA lining cells may be responsible for cell adhesion and migration into the diseased STs. Therapies targeting this novel signaling pathway may be beneficial in RA.