Mechanical strain determines the site-specific localization of inflammation and tissue damage in arthritis

被引：147

作者：

Cambre, Isabelle ^{[1
,2
]}

Gaublomme, Djoere ^{[1
,2
]}

Burssens, Arne ^{[1
,2
,3
]}

Jacques, Peggy ^{[1
,2
]}

Schryvers, Nadia ^{[1
,2
]}

De Muynck, Amelie ^{[4
]}

Meuris, Leander ^{[5
,6
]}

Lambrecht, Stijn ^{[1
,2
]}

Carter, Shea ^{[7
,8
]}

de Bleser, Pieter ^{[9
]}

Saeys, Yvan ^{[9
]}

Van Hoorebeke, Luc ^{[4
]}

Kollias, George ^{[10
,11
]}

Mack, Matthias ^{[12
]}

Simoens, Paul ^{[13
]}

Lories, Rik ^{[7
,8
]}

Callewaert, Nico ^{[5
,6
]}

Schett, Georg ^{[14
,15
]}

Elewaut, Dirk ^{[1
,2
]}

机构：

[1] VIB Inflammat Res Ctr IRC, Unit Mol Immunol & Inflammat, Technol Pk 927, B-9052 Ghent, Belgium

[2] Univ Ghent, Ghent Univ Hosp, Dept Rheumatol, De Pintelaan 185, B-9000 Ghent, Belgium

[3] Ghent Univ Hosp, Dept Orthopaed & Traumatol, De Pintelaan 185, B-9000 Ghent, Belgium

[4] Univ Ghent, UGCT Dept Phys & Astron, Proeftuinstr 86, B-9000 Ghent, Belgium

[5] VIB Inflammat Res Ctr IRC, Unit Med Biotechnol, Technol Pk 927, B-9052 Ghent, Belgium

[6] Univ Ghent, Dept Biochem & Microbiol, Lab Prot Biochem & Biomol Engn, Technol Pk 927, B-9000 Ghent, Belgium

[7] Katholieke Univ Leuven, Dept Dev & Regenerat, Lab Tissue Homeostasis & Dis, Skeletal Biol & Engn Res Ctr, Herestr 49, B-3000 Leuven, Belgium

[8] Univ Hosp Leuven, Div Rheumatol, Herestr 49, B-3000 Leuven, Belgium

[9] VIB Ctr Inflammat Res, Data Min & Modeling Biomed, Technol Pk 927, B-9052 Ghent, Belgium

[10] Biomed Sci Res Ctr Alexander Fleming, Div Immunol, 34 Fleming St, Vari 16672, Attica, Greece

[11] Univ Athens, Sch Med, Dept Expt Physiol, 75 Mikras Asias St, Athens 11527, Greece

[12] Univ Hosp Regensburg, Dept Internal Med Nephrol 2, D-93402 Regensburg, Germany

[13] Univ Ghent, Fac Vet Med, Dept Morphol, Salisburylaan 133, B-9820 Merelbeke, Belgium

[14] Friedrich Alexander Univ Erlangen Nuremberg, Dept Internal Med 3, Rheumatol & Immunol, Ulmenweg 18, D-91054 Erlangen, Germany

[15] Univ Klinikum, Ulmenweg 18, D-91054 Erlangen, Germany

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

关键词：

RHEUMATOID-ARTHRITIS; JOINT; AUTOIMMUNITY; OSTEOCLASTS; RESOLUTION; MONOCYTES; DISEASE; CELLS; TNF;

D O I：

10.1038/s41467-018-06933-4

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Many pro-inflammatory pathways leading to arthritis have global effects on the immune system rather than only acting locally in joints. The reason behind the regional and patchy distribution of arthritis represents a longstanding paradox. Here we show that biomechanical loading acts as a decisive factor in the transition from systemic autoimmunity to joint inflammation. Distribution of inflammation and erosive disease is confined to mechano-sensitive regions with a unique microanatomy. Curiously, this pathway relies on stromal cells but not adaptive immunity. Mechano-stimulation of mesenchymal cells induces CXCL1 and CCL2 for the recruitment of classical monocytes, which can differentiate into bone-resorbing osteoclasts. Genetic ablation of CCL2 or pharmacologic targeting of its receptor CCR2 abates mechanically-induced exacerbation of arthritis, indicating that stress-induced chemokine release by mesenchymal cells and chemo-attraction of monocytes determines preferential homing of arthritis to certain hot spots. Thus, mechanical strain controls the site-specific localisation of inflammation and tissue damage in arthritis.

引用

页数：14

共 35 条

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[2]

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