Specific antibody protection of the extracellular cartilage matrix against collagen antibody-induced damage

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Specific antibody protection of the extracellular cartilage matrix against collagen antibody-induced damage

Croxford, Allyson M. (author): Monash University, Clayton, Australia

Crombie, Duncan (author): Monash University, Clayton, Australia

McNaughton, Donald (author): Monash University, Clayton, Australia

Holmdahl, Rikard (author): Karolinska Institutet,Karolinska Institute, Stockholm, Sweden

Nandakumar, Kutty Selva, 1965- (author): Karolinska Institutet,Karolinska Institute, Stockholm, Sweden

Rowley, Merrill J. (author): Monash University, Clayton, Australia

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(creator_code:org_t)

2010-07-26
2010
English.
In: Arthritis and Rheumatism. - Hoboken, NJ : John Wiley & Sons. - 0004-3591 .- 1529-0131. ; 62:11, s. 3374-3384

Related links:: https://doi.org/10.1...; show more...; https://onlinelibrar...; https://urn.kb.se/re...; https://doi.org/10.1...; http://kipublication...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

OBJECTIVE: The type II collagen (CII)-specific monoclonal antibodies (mAb) M2139 and CIIC1 induce arthritis in vivo and degrade bovine cartilage explants in vitro, whereas mAb CIIF4 is nonarthritogenic and prevents arthritis development when given in combination with M2139 and CIIC1. To determine the nature of the protective capacity of CIIF4 antibody, we examined the effects of adding CIIF4 to cartilage explants cultured in vitro with M2139 and CIIC1. METHODS: Bovine cartilage explants were cultured in the presence of M2139 and CIIC1, with or without CIIF4. Histologic changes were examined, and chemical changes to collagens and proteoglycans were assessed by Fourier transform infrared microspectroscopy (FTIRM). Fresh cartilage and cartilage that had been freeze-thawed to kill chondrocytes cultured with or without the addition of GM6001, a broad-spectrum inhibitor of matrix metalloproteinases (MMPs), were compared using FTIRM analysis. RESULTS: M2139 and CIIC1 caused progressive degradation of the cartilage surface and loss of CII, even in the absence of viable chondrocytes. CIIF4 did not cause cartilage damage, and when given with the arthritogenic mAb, it prevented their damage and permitted matrix regeneration, a process that required viable chondrocytes. Inhibition of MMP activity reduced cartilage damage but did not mimic the effects of CIIF4. CONCLUSION: CII-reactive antibodies can cause cartilage damage or can be protective in vivo and in vitro, depending on their epitope specificity. Since CII antibodies of similar specificity also occur in rheumatoid arthritis in humans, more detailed studies should unravel the regulatory mechanisms operating at the effector level of arthritis pathogenesis. © 2010 by the American College of Rheumatology.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)

Keyword

Analysis of Variance
Animals
Antibodies
Monoclonal/*pharmacology
Cartilage/*immunology/metabolism/pathology
Cattle
Chondrocytes/*immunology/metabolism/pathology
Collagen Type II/*immunology
Extracellular Matrix/*immunology/metabolism/pathology
Matrix Metalloproteinases/immunology/metabolism
Proteoglycans/immunology/metabolism
Spectroscopy
Fourier Transform Infrared
Tissue Culture Techniques

Publication and Content Type

ref (subject category)
art (subject category)

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By the author/editor: Croxford, Allyso ...; Crombie, Duncan; McNaughton, Dona ...; Holmdahl, Rikard; Nandakumar, Kutt ...; Rowley, Merrill ...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Rheumatology and ...

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By the university: Halmstad University; Karolinska Institutet

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