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Title: Noggin haploinsufficiency differentially affects tissue responses in destructive and remodeling arthritis
Authors: Lories, Rik ×
Daans, Melina
Derese, Inge
Matthys, Patrick
Kasran, Ahmad
Tylzanowski, Przemyslaw
Ceuppens, Jan
Luyten, Frank #
Issue Date: Jun-2006
Publisher: John Wiley & Sons
Series Title: Arthritis and Rheumatism vol:54 issue:6 pages:1736-1746
Abstract: OBJECTIVE: The balance between destruction and homeostatic or reparative responses determines the outcome of arthritis. Increasing evidence suggests a role for signaling pathways, essential for development and growth, in the maintenance of tissue homeostasis and attempts at repair. Inappropriate activation of such pathways may also have a role in disease progression. We undertook this study to determine the effect of shifting the balance in bone morphogenetic protein (BMP) signaling in different mouse models of arthritis. METHODS: Endogenous levels of noggin, a BMP antagonist, were reduced using heterozygous noggin(+/LacZ) mice in a model of inflammation-driven destruction (methylated bovine serum albumin [mBSA]-induced monarthritis), a model of systemic autoimmune arthritis (collagen-induced arthritis [CIA]), and a model of joint ankylosis (spontaneous arthritis in DBA/1 mice). In addition, we studied BMP inactivation by adenoviral noggin overexpression in destructive arthritis. Cartilage damage and activation of BMP signaling were studied by digital image analysis using Safranin O sulfated glycosaminoglycan staining and immunohistochemistry for phosphorylated Smads (Smads 1, 5, and 8), respectively. RESULTS: Noggin haploinsufficiency provided protection for articular cartilage against destruction in mBSA-induced arthritis. Antagonist overexpression rendered cartilage more vulnerable in this model. Noggin gene transfer in knees affected by CIA also enhanced cartilage damage. Haploinsufficiency did not affect CIA, but noggin(+/LacZ) mice had an increased number of CD4-positive cells with normal immune responses. In noggin(+/LacZ) DBA/1 mice with spontaneous arthritis, we observed delayed progression from cartilage to bone formation. CONCLUSION: Tight spatiotemporal control of BMP signaling appears to be critical in the response of joint tissues in models of arthritis.
URI: 
ISSN: 0004-3591
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Rheumatology Section (-)
Laboratory of Immunobiology (Rega Institute)
Laboratory of Clinical Immunology
Laboratory for Intensive Care Medicine (-)
Laboratory of Intensive Care Medicine
× corresponding author
# (joint) last author

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