title: Changes in focal adhesion kinase expression in rats with collagen-induced arthritis and efficacy of intervention with disease modifying anti-rheumatic drugs alone or in combination.
abstract: Focal adhesion kinase (FAK) is known to promote the proliferation, migration and survival of synovial cells and plays an important role in the occurrence, development and pathological process of rheumatoid arthritis (RA). The aim of the present study was to observe FAK changes in synovial cells of rats with collagen-induced arthritis (CIA) and after intervention with disease modifying anti-rheumatic drugs (DMARDs) alone or in combination in a CIA female SD rat model induced by collagen type II. The rats were randomized to 8 groups: normal control group, CIA model control group, methotrexate (MTX, 0.9 mg/kg/w) group, cyclophosphamide (CTX, 24 mg/kg/3 w) group, leflunomide (LEF, 1.2 mg/kg/d) group, MTX + CTX group, LEF + CTX group, and MTX + LEF group. They were intervened with DMARDs alone or in combination for six weeks. The experiment lasted a total of 9 weeks in vivo. Articular inflammation was measured during the process of drug intervention in terms of the degree of swelling degree in the right hind foot using a venire caliper. All animals were sacrificed by breaking the neck after 9 weeks. Then, the ankle was fixed, decalcified, embedded, and HE stained, and prepared into slices to observe pathological changes in the synovial tissue. FAK expression in synovial cells was assayed by immunohistochemistry and the mean optical density (OD) value was measured using the HPIAS-2000 image analysis system. It was found that FAK expression was negative in normal control group, positive in CIA model control group, and decreased in the three DMARD combination treatment groups significantly as compared with that in the three single-drug groups (P < 0.05). FAK expression in LEF + CTX group or MTX + CTX group decreased more significantly than that in MTX + LEF group (P < 0.05), and there was no statistically significant difference between LEF + CTX and MTX + CTX groups. The arthritis index and pathological change in the synovial tissue in LEF + CTX group or MTX + CTX group were improved more significantly than those in MTX + LEF group or single-drug groups. Our results showed that FAK expression was positive in CIA rats, indicating that it played an important role in the pathogenesis of RA, and that intervention with DMARDs could reduce the FAK expression in synovial cells of CIA rats. We hope these findings would contribute to the treatment of RA and other rheumatic diseases by reducing adhesion, proliferation and migration of synovial cells and inhibiting the over-expression of FAK.
authors.affiliation: Department of Rheumatology, The Second Hospital, Shanxi Medical University Taiyuan 030001, Shanxi, China.
authors.forename: Hui-Ying
authors.initials: HY
authors.lastname: Gao
authors.affiliation: Department of Rheumatology, The Second Hospital, Shanxi Medical University Taiyuan 030001, Shanxi, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Rheumatology, The Second Hospital, Shanxi Medical University Taiyuan 030001, Shanxi, China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Li
authors.affiliation: Department of Rheumatology, The Second Hospital, Shanxi Medical University Taiyuan 030001, Shanxi, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Lv
authors.affiliation: Department of Rheumatology, The Second Hospital, Shanxi Medical University Taiyuan 030001, Shanxi, China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Wen
authors.affiliation: Department of Medicine, Shanxi Tumor Hospital Taiyuan 030013, Shanxi, China.
authors.forename: Qing-Zhen
authors.initials: QZ
authors.lastname: Song
authors.affiliation: Department of Rheumatology, The Second Hospital, Shanxi Medical University Taiyuan 030001, Shanxi, China.
authors.forename: Wen-Peng
authors.initials: WP
authors.lastname: Zhao
authors.affiliation: Department of Rheumatology, The Second Hospital, Shanxi Medical University Taiyuan 030001, Shanxi, China.
authors.forename: Xiang-Cong
authors.initials: XC
authors.lastname: Zhao
authors.affiliation: Department of Rheumatology, The Second Hospital, Shanxi Medical University Taiyuan 030001, Shanxi, China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Zhang
authors.affiliation: Department of Rheumatology, The Second Hospital, Shanxi Medical University Taiyuan 030001, Shanxi, China.
authors.forename: Si-Yu
authors.initials: SY
authors.lastname: Zhang
authors.affiliation: Department of Physiology, School of Medicine, Shanghai Jiaotong University Shanghai 200025, China.
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Zhi
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D024043:Collagen Type II; D003520:Cyclophosphamide / Q000494:pharmacology; D004359:Drug Therapy, Combination; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D007555:Isoxazoles / Q000494:pharmacology; D007596:Joints / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D000077339:Leflunomide; D008727:Methotrexate / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D013583:Synovial Membrane / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D013997:Time Factors
chemical_list: D018501:Antirheumatic Agents; D024043:Collagen Type II; D007555:Isoxazoles; D003520:Cyclophosphamide; D051417:Focal Adhesion Kinase 1; C496052:Ptk2 protein, rat; D000077339:Leflunomide; D008727:Methotrexate
keywords: Focal adhesion kinase; collagen-induced arthritis; disease modifying anti-rheumatic drug (DMARD); rheumatoid arthritis (RA)