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01.07.2012 | Original Research

Downregulation of the Inflammatory Response by CORM-3 Results in Protective Effects in a Model of Postmenopausal Arthritis

verfasst von: Lidia Ibáñez, Maria José Alcaraz, Nuria Maicas, David Guede, José Ramón Caeiro, Roberto Motterlini, Maria Luisa Ferrándiz

Erschienen in: Calcified Tissue International | Ausgabe 1/2012

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Abstract

CO-releasing molecules (CORMs) are a new class of drugs able to release small amounts of CO in biological systems. We have shown previously that one of these molecules, CORM-3, exerts anti-inflammatory effects in animal models. The aim of this study was to assess the effects of CORM-3 on bone metabolism in a model of postmenopausal rheumatoid arthritis osteoporosis. Ovariectomy was followed by collagen-induced arthritis in female DBA-1/J mice. Animals showing arthritis on day 22 after immunization were then randomized into control and treatment groups. CORM-3 was administered at 10 mg/kg, intraperitoneally, once a day. Alendronate was administered at 100 μg/kg, orally, once a day. On days 36 and 50 after immunization, animals were killed and tissues analyzed. The arthritic score was significantly reduced by CORM-3 but not by alendronate treatment. Histopathological analyses indicated that both compounds reduced cellular infiltration and cartilage degradation. Local bone erosion and reduction in TNFα levels were seen for CORM-3 on day 50 and for alendronate on day 36. Serum levels of COMP, IL-6, MMP-3, CTX-I, alkaline phosphatase, and osteocalcin were decreased by both treatments, whereas TNFα levels were reduced by CORM-3 and TRAP-5b by alendronate. Micro-computed tomographic analysis showed protective effects on trabecular bone, which were more prominent for CORM-3 on day 36 and for alendronate on day 50. Our results suggest that CORMs represent a novel anti-inflammatory strategy to counteract joint bone erosion with partial protective effects on systemic bone loss in postmenopausal rheumatoid arthritis.

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Titel: Downregulation of the Inflammatory Response by CORM-3 Results in Protective Effects in a Model of Postmenopausal Arthritis
verfasst von: Lidia Ibáñez
Maria José Alcaraz
Nuria Maicas
David Guede
José Ramón Caeiro
Roberto Motterlini
Maria Luisa Ferrándiz
Publikationsdatum: 01.07.2012
Verlag: Springer-Verlag
Erschienen in: Calcified Tissue International / Ausgabe 1/2012
Print ISSN: 0171-967X
Elektronische ISSN: 1432-0827
DOI: https://doi.org/10.1007/s00223-012-9612-7

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Downregulation of the Inflammatory Response by CORM-3 Results in Protective Effects in a Model of Postmenopausal Arthritis

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