Fcγ receptors directly mediate cartilage, but not bone, destruction in murine antigen-induced arthritis -: Uncoupling of cartilage damage from bone erosion and joint inflammation

被引:51
作者
Van Lent, Peter L.
Grevers, Lilyanne
Lubberts, Erik
de Vries, Teun J.
Nabbe, Karin C.
Verbeek, Sjef
Oppers, Birgit
Sloetjes, Annet
Blom, Arjen B.
van den Berg, Wim B.
机构
[1] Radboud Univ Nijmegen, Med Ctr, Dept Rheumatol, NL-6500 HB Nijmegen, Netherlands
[2] Univ Amsterdam, Acad Ctr Dent, NL-1012 WX Amsterdam, Netherlands
[3] Vrije Univ Amsterdam, NL-1081 HV Amsterdam, Netherlands
[4] Leiden Univ, Med Ctr, NL-2300 RA Leiden, Netherlands
来源
ARTHRITIS AND RHEUMATISM | 2006年 / 54卷 / 12期
关键词
D O I
10.1002/art.22253
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective. To determine the relationship between synovial inflammation and the concomitant occurrence of cartilage and bone erosion during conditions of variable inflammation using various Fc gamma receptor knockout (Fc gamma R-/-) mice. Methods. Antigen-induced arthritis (AIA) was introduced in the knee joints of various Fc gamma R-/- mice and wild-type controls. joint inflammation and cartilage and bone destruction levels were determined by histologic analysis. Cathepsin K, RANKL, and osteoprotegerin (OPG) levels were detected by immunolocalization. Results. In Fc gamma RIIb(-/-) mice, which lack the inhibiting Fc gamma receptor IIb, levels of joint inflammation and cartilage and bone destruction were significantly higher (infiltrate 93%, exudate 200%, cartilage 100%, bone 156%). AIA in mice lacking activating Fc gamma R types I, III, and IV, but not Fc gamma RIIb (FcR gamma-chain(-/-) mice), prevented cartilage destruction completely. In contrast, levels of bone erosion and joint inflammation were comparable with their wild-type controls. Of great interest, in arthritic mice lacking activating Fc gamma R types I, II, and III, but not IV (Fc gamma RI/II/III-/- mice), levels of joint inflammation were highly elevated (infiltrate and exudate, 100% and 188%, respectively). Cartilage destruction levels were decreased by 92%, whereas bone erosion was increased by 200%. Cathepsin K, a crucial mediator of osteoclasts, showed a strong correlation with the amount of inflammation but not with the amount of activating Fc gamma R, which was low in osteoclasts. RANKL, but not OPG, levels were higher in the inflammatory cells of arthritic knee joints of Fc gamma RI/II/ III-/- mice versus wild-type mice. Conclusion. Activating Fc gamma R are crucial in mediating cartilage destruction independently of joint inflammation. In contrast, Fc gamma R are not directly involved in bone erosion. Indirectly, Fc gamma R drive bone destruction by regulating joint inflammation.
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收藏
页码:3868 / 3877
页数:10
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