Coordinate expression of activating Fcγ receptors I and III and inhibiting Fcγ receptor type II in the determination of joint inflammation and cartilage destruction during immune complex–mediated arthritis

Nabbe, Karin C.; Blom, A.B.; Holthuysen, A.E.M.; Boross, Péter; Roth, Johannes; Verbeek, Sjef; Lent, P.L.E.M. van; Berg, Wim B. van den

doi:10.1002/art.10721

Cited by 63 publications

(61 citation statements)

References 54 publications

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“…In the S100A8/A9 heterodimer complex, S100A8 is the active component, and S100A9 stabilizes S100A8 to prevent its degradation (7). Recently, we demonstrated that in murine macrophages, S100A8, independent of complex formation with S100A9, up-regulated activating Fc␥ receptors and metalloproteinases, which are important mediators of cartilage destruction in arthritis (26,27). Additionally, we demonstrated that S100A9 and the heterodimer complex were much less potent (16,28).…”

Section: Discussionmentioning

confidence: 81%

S100A8 enhances osteoclastic bone resorption in vitro through activation of Toll‐like receptor 4: Implications for bone destruction in murine antigen‐induced arthritis

Grevers¹,

Vries²,

Vogl³

et al. 2011

Arthritis & Rheumatism

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Objective. Rheumatoid arthritis, which is associated with elevated levels of S100A8 and S100A9, is characterized by severe bone erosions caused by enhanced osteoclast formation and activity. The aim of the present study was to investigate the role of S100A8 and S100A9 in osteoclastic bone destruction in murine antigen-induced arthritis (AIA).Methods. Bone destruction was analyzed in the arthritic knee joints of S100A9-deficient mice in which S100A8 protein expression was also lacking, and in wild-type (WT) controls. Osteoclast precursors from S100A9-deficient and WT mice were differentiated into osteoclasts in vitro. Additionally, precursors were stimulated with S100A8, S100A9, or S100A8/A9 during osteoclastogenesis. Receptor involvement was investigated using an anti-receptor for advanced glycation end products (anti-RAGE)-blocking antibody, soluble RAGE, or Toll-like receptor 4 (TLR-4)-deficient osteoclast precursors. The formation of osteoclasts and actin rings, the regulation of osteoclast markers, and bone resorption were analyzed.Results. Bone erosions and cathepsin K staining were significantly suppressed in S100A9-deficient mice after AIA induction. However, osteoclast precursors from S100A9-deficient mice developed normally into functional osteoclasts, which excludes a role for intrinsic S100A8/A9. In contrast to the results observed with S100A9 and S100A8/A9, the addition of S100A8 during osteoclastogenesis resulted in stimulation of osteoclast formation in conjunction with enhanced actin ring formation and increased bone resorption. Analysis of the putative receptor for S100A8 in osteoclastogenesis revealed that osteoclast differentiation and function could not be inhibited by blocking RAGE, whereas the increase in osteoclast numbers and enhanced bone resorption were completely abrogated using TLR-4-deficient osteoclast precursors.Conclusion. These results demonstrate that S100A8 stimulated osteoclast formation and activity and suggest that both S100A8 and TLR-4 are important factors in mediating osteoclastic bone destruction in experimental arthritis.Bone erosions are an important hallmark of rheumatoid arthritis (RA) and typically result from enhanced formation and activity of osteoclasts in affected joints. Osteoclasts originate from hematopoietic precursors of the monocyte/macrophage lineage that differentiate into multinucleated osteoclasts under the

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Section: Discussionmentioning

confidence: 81%

S100A8 enhances osteoclastic bone resorption in vitro through activation of Toll‐like receptor 4: Implications for bone destruction in murine antigen‐induced arthritis

Grevers¹,

Vries²,

Vogl³

et al. 2011

Arthritis & Rheumatism

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“…The requirement for the expression of activating FcgR for disease manifestations has been demonstrated in several animal models of arthritis, including arthritis induced either by collagen 25 or immune complexes, 26,27 and in the newly described animal model for RA, the K/BxN mouse. 28 In addition, mice deficient in the inhibitory FcgRIIb develop accelerated joint disease providing further evidence for the importance of FcgR in animal models of RA.…”

Section: Introductionmentioning

confidence: 99%

FcγR expression on NK cells influences disease severity in rheumatoid arthritis

et al. 2004

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“…Studies of RA and arthritis in animal models demonstrate that Fc␥R are crucial players in the pathogenesis of arthritis (11)(12)(13)(14)(15)(16). It has been shown that activation of infiltrating or resident cells in the joint leads to severe cartilage destruction, such as matrix metalloproteinase-induced damage or chondrocyte death (17).…”

mentioning

confidence: 99%

Destructive Arthritis in the Absence of Both FcγRI and FcγRIII

Boross

Lent²,

Martín-Ramírez

et al. 2008

The Journal of Immunology

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Fc receptors for IgG (FcγR) have been implicated in the development of arthritis. However, the precise contribution of the individual FcγR to joint pathology is unclear. In this study, the role of the different FcγR was assessed both in an active and in a passive mouse model of arthritis by analyzing disease development in double and triple knockout (KO) offspring from crosses of FcγRI KO, FcγRIII KO, FcγRI/III double KO, or FcR γ-chain KO with the FcγRII KO on C57BL6 background, which is susceptible for collagen-induced arthritis (CIA). In the active CIA model, onset was significantly delayed in the absence of FcγRIII, whereas incidence and maximum severity were significantly decreased in FcγRI/II/III triple KO but not in FcγRII/III double KO and FcγRI/II double KO mice as compared with FcγRII KO animals. Remarkably, fully destructive CIA developed in FcγRI/II/III triple KO mice. In contrast, FcR γ/FcγRII double KO mice were resistant to CIA. These findings were confirmed with the passive KRN serum-induced arthritis model. These results indicate that all activating FcγR play a role in the development of arthritis, mainly in the downstream effector phase. FcγRIII is critically required for early arthritis onset, and FcγRI can substantially contribute to arthritis pathology. Importantly, FcγRI and FcγRIII were together dispensable for the development of destructive arthritis but the FcR γ-chain was not, suggesting a role for another FcR γ-chain associated receptor, most likely FcγRIV. In addition, FcγRII plays a negative regulatory role in both the central and effector phase of arthritis.

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Coordinate expression of activating Fcγ receptors I and III and inhibiting Fcγ receptor type II in the determination of joint inflammation and cartilage destruction during immune complex–mediated arthritis

Cited by 63 publications

References 54 publications

S100A8 enhances osteoclastic bone resorption in vitro through activation of Toll‐like receptor 4: Implications for bone destruction in murine antigen‐induced arthritis

S100A8 enhances osteoclastic bone resorption in vitro through activation of Toll‐like receptor 4: Implications for bone destruction in murine antigen‐induced arthritis

FcγR expression on NK cells influences disease severity in rheumatoid arthritis

Destructive Arthritis in the Absence of Both FcγRI and FcγRIII

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