TY - JOUR
T1 - Role of Fc receptor γ chain in inflammation and cartilage damage during experimental antigen-induced arthritis
AU - van Lent, P. L.E.M.
AU - van Vuuren, A.
AU - Blom, A. B.
AU - Holthuysen, A. E.M.
AU - van De Putte, L. B.A.
AU - van De Winkel, J. G.J.
AU - van Den Berg, W. B.
N1 - Copyright © 2000 by the American College of Rheumatology
PY - 2000/4
Y1 - 2000/4
N2 - Objective. To study the role of Fc receptor (FcR) γ chain in inflammation and cartilage destruction during antigen-induced arthritis (AIA). Methods. FcR γ-/- mice and controls were immunized with methylated bovine serum albumin (mBSA) in Freund's complete adjuvant, followed by induction of arthritis by local injection of mBSA into the right knee joint. Joint inflammation was studied by 99mTc uptake and by histology. Breakdown of proteoglycans from the cartilage matrix was determined by loss of red staining in Safranin O-stained knee joint sections, and matrix metalloproteinase (MMP)-mediated aggrecan degradation was determined by immunolocalization using anti-VDIPEN antibodies. Chondrocyte death was measured by determining empty lacunae in hematoxylin-stained sections and with the TUNEL assay in cryostat sections. Erosion was detected as ruffling of the cartilage surface. Results. Joint swelling, as measured by 99mTc uptake on days 1, 3, and 7, was significantly decreased in FcR γ-/- mice compared with controls. On day 7 after AIA induction, sustained joint inflammation, as seen histologically, was not significantly lower in FcR γ-/- deficient mice. In various cartilage layers (femur, tibia, patella) of control arthritic knee joints, marked depletion of proteoglycans (40-70%), chondrocyte death (25-50%), and mild surface erosion were found. In FcR γ-/- knee joints, depletion of proteoglycans was comparable (40-70%). Strikingly, chondrocyte death and matrix erosion were absent. Furthermore, MMP-induced aggrecan neoepitopes, which were abundantly found in controls, were also absent in FcR γ-/-. Nevertheless, latent MMPs were present in the cartilage matrix as seen in APMA-activated patellae. Conclusion. FcR γ chain is involved in the severity of acute and sustained inflammation and is a crucial factor in cartilage erosion during AIA, probably by regulating activation of latent MMPs present in the cartilage matrix.
AB - Objective. To study the role of Fc receptor (FcR) γ chain in inflammation and cartilage destruction during antigen-induced arthritis (AIA). Methods. FcR γ-/- mice and controls were immunized with methylated bovine serum albumin (mBSA) in Freund's complete adjuvant, followed by induction of arthritis by local injection of mBSA into the right knee joint. Joint inflammation was studied by 99mTc uptake and by histology. Breakdown of proteoglycans from the cartilage matrix was determined by loss of red staining in Safranin O-stained knee joint sections, and matrix metalloproteinase (MMP)-mediated aggrecan degradation was determined by immunolocalization using anti-VDIPEN antibodies. Chondrocyte death was measured by determining empty lacunae in hematoxylin-stained sections and with the TUNEL assay in cryostat sections. Erosion was detected as ruffling of the cartilage surface. Results. Joint swelling, as measured by 99mTc uptake on days 1, 3, and 7, was significantly decreased in FcR γ-/- mice compared with controls. On day 7 after AIA induction, sustained joint inflammation, as seen histologically, was not significantly lower in FcR γ-/- deficient mice. In various cartilage layers (femur, tibia, patella) of control arthritic knee joints, marked depletion of proteoglycans (40-70%), chondrocyte death (25-50%), and mild surface erosion were found. In FcR γ-/- knee joints, depletion of proteoglycans was comparable (40-70%). Strikingly, chondrocyte death and matrix erosion were absent. Furthermore, MMP-induced aggrecan neoepitopes, which were abundantly found in controls, were also absent in FcR γ-/-. Nevertheless, latent MMPs were present in the cartilage matrix as seen in APMA-activated patellae. Conclusion. FcR γ chain is involved in the severity of acute and sustained inflammation and is a crucial factor in cartilage erosion during AIA, probably by regulating activation of latent MMPs present in the cartilage matrix.
UR - https://www.scopus.com/pages/publications/0033857239
U2 - 10.1002/1529-0131(200004)43:4<740::AID-ANR4>3.0.CO;2-0
DO - 10.1002/1529-0131(200004)43:4<740::AID-ANR4>3.0.CO;2-0
M3 - Article
C2 - 10765918
AN - SCOPUS:0033857239
SN - 0004-3591
VL - 43
SP - 740
EP - 752
JO - Arthritis and Rheumatism
JF - Arthritis and Rheumatism
IS - 4
ER -