Cartilage damage and bone erosion are more prominent determinants of functional impairment in longstanding experimental arthritis than synovial inflammation

被引：46

作者：

Hayer, Silvia ^{[1
]}

Bauer, Gregor ^{[1
,3
]}

Willburger, Martin ^{[1
,4
]}

Sinn, Katharina ^{[1
]}

Alasti, Farideh ^{[1
]}

Plasenzotti, Roberto ^{[2
]}

Shvets, Tetyana ^{[1
]}

Niederreiter, Birgit ^{[1
]}

Aschauer, Constantin ^{[1
,5
]}

Steiner, Guenter ^{[1
]}

Podesser, Bruno K. ^{[2
]}

Smolen, Josef S. ^{[1
]}

Redlich, Kurt ^{[1
]}

机构：

[1] Med Univ Vienna, Dept Internal Med 3, Div Rheumatol, A-1090 Vienna, Austria

[2] Med Univ Vienna, Div Biomed Res, A-1090 Vienna, Austria

[3] Kaiser Franz Josef Spital, Dept Neurol, A-1100 Vienna, Austria

[4] Landeskrankenhaus Rankweil, Dept Neurol, A-26830 Rankweil, Austria

[5] Med Univ Vienna, Dept Internal Med 3, Div Nephrol, A-1090 Vienna, Austria

来源：

DISEASE MODELS & MECHANISMS | 2016年 / 9卷 / 11期

关键词：

Functional impairment; Inflammatory joint damage; Rheumatoid arthritis animal model; TNF blockade; COLLAGEN-INDUCED ARTHRITIS; TUMOR-NECROSIS-FACTOR; RHEUMATOID-ARTHRITIS; JOINT DAMAGE; GAIT ANALYSIS; RADIOGRAPHIC DAMAGE; PHYSICAL FUNCTION; MURINE MODEL; MICE; COMBINATION;

D O I：

10.1242/dmm.025460

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Chronic inflammation of articular joints causing bone and cartilage destruction consequently leads to functional impairment or loss of mobility in affected joints from individuals affected by rheumatoid arthritis (RA). Even successful treatment with complete resolution of synovial inflammatory processes does not lead to full reversal of joint functionality, pointing to the crucial contribution of irreversibly damaged structural components, such as bone and cartilage, to restricted joint mobility. In this context, we investigated the impact of the distinct components, including synovial inflammation, bone erosion or cartilage damage, as well as the effect of blocking tumor necrosis factor (TNF) on functional impairment in human-TNF transgenic (hTNFtg) mice, a chronic inflammatory erosive animal model of RA. We determined CatWalk-assisted gait profiles as objective quantitative measurements of functional impairment. We first determined bodyweight- independent gait parameters, including maximum intensity, print length, print width and print area in wild-type mice. We observed early changes in those gait parameters in hTNFtgmice at week 5-the first clinical signs of arthritis. Moreover, we found further gait changes during chronic disease development, indicating progressive functional impairment in hTNFtg mice. By investigating the association of gait parameters with inflammation-mediated joint pathologies at different time points of the disease course, we found a relationship between gait parameters and the extent of cartilage damage and bone erosions, but not with the extent of synovitis in this chronicmodel. Next, we observed a significant improvement of functional impairment upon blocking TNF, even at progressed stages of disease. However, blocking TNF did not restore full functionality owing to remaining subclinical inflammation and structural microdamage. In conclusion, CatWalk gait analysis provides a useful tool for quantitative assessment of functional impairment in inflammatory destructive arthritis. Our findings indicate that cartilage damage and bone erosion, but not synovial inflammation, are the most important determinants for progressive functional impairment in this chronic erosive arthritis model.

引用

页码：1329 / 1338

页数：10

共 38 条

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