The loss of α2β1 integrin suppresses joint inflammation and cartilage destruction in mouse models of rheumatoid arthritis

Autor: Beate Eckes, Svetlana Frank, Doreen Wendholt, Wim B. van den Berg, Simon Strietholt, Adelheid Korb-Pap, Noreen Pundt, Leo A. B. Joosten, Marvin A. Peters, Thomas Pap, George Kollias
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Cartilage
Articular
Male
Pathology
medicine.medical_specialty
Immunology
Integrin
Medizin
Arthritis
Inflammation
Matrix metalloproteinase
Arthritis
Rheumatoid
Mice
Chondrocytes
Rheumatology
Cell Adhesion
medicine
Animals
Humans
Immunology and Allergy
Inbreeding
Pharmacology (medical)
Fibroblast
Cell Proliferation
Mice
Knockout
Synovitis
Hereditary cancer and cancer-related syndromes [ONCOL 1]
biology
Tumor Necrosis Factor-alpha
business.industry
Cartilage
Pathogenesis and modulation of inflammation Infection and autoimmunity [N4i 1]
Fibroblasts
medicine.disease
Arthritis
Experimental
Stifle
Infection and autoimmunity Auto-immunity
transplantation and immunotherapy [NCMLS 1]
Mice
Inbred C57BL
Disease Models
Animal
Destructive Arthritis
medicine.anatomical_structure
biology.protein
Cancer research
Female
Matrix Metalloproteinase 3
Tumor necrosis factor alpha
Integrin alpha2beta1
medicine.symptom
business
Zdroj: Arthritis and Rheumatism, 64, 1359-68
Arthritis and Rheumatism, 64, 5, pp. 1359-68
ISSN: 0004-3591
Popis: Item does not contain fulltext OBJECTIVE: Integrin alpha2beta1 functions as a major receptor for type I collagen on different cell types, including fibroblasts and inflammatory cells. Although in vitro data suggest a role for alpha2beta1 integrin in regulating both cell attachment and expression of matrix-degrading enzymes such as matrix metalloproteinases (MMPs), mice that lack the alpha2 integrin subunit (Itga2(-/-) mice) develop normally and are fertile. We undertook this study to investigate the effect of Itga2 deficiency in 2 different mouse models of destructive arthritis: the antigen-induced arthritis (AIA) mouse model and the human tumor necrosis factor alpha (TNFalpha)-transgenic mouse model. METHODS: AIA was induced in the knee joints of Itga2(-/-) mice and wild-type controls. Human TNF-transgenic mice were crossed with Itga2(-/-) mice and were assessed clinically and histopathologically for signs of arthritis, inflammation, bone erosion, and cartilage damage. MMP expression, proliferation, fibroblast attachment, and ERK activation were determined. RESULTS: Under arthritic conditions, Itga2 deficiency led to decreased severity of joint pathology. Specifically, Itga2(-/-) mice showed less severe clinical symptoms and dramatically reduced pannus formation and cartilage erosion. Mice lacking alpha2beta1 integrin exhibited reduced MMP-3 expression, both in their sera and in fibroblast-like synoviocytes (FLS), due to impaired ERK activation. Further, both the proliferation and attachment of FLS to cartilage were partially dependent on alpha2beta1 integrin in vitro and in vivo. CONCLUSION: Our findings suggest that alpha2beta1 integrin contributes significantly to inflammatory cartilage destruction by promoting fibroblast proliferation and attachment and MMP expression. 01 mei 2012
Databáze: OpenAIRE
Externí odkaz: