Downregulation of the inflammatory response by CORM-3 results in protective effects in a model of postmenopausal arthritis.
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.
Department of Pharmacology, University of Valencia, Av. Vicent Andres Estelles s/n, 46100, Burjassot, Valencia, Spain.
Lidia
L
Ibáñez
Maria José
MJ
Alcaraz
Nuria
N
Maicas
David
D
Guede
José Ramón
JR
Caeiro
Roberto
R
Motterlini
Maria Luisa
ML
Ferrándiz
D019386:Alendronate / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001168:Arthritis / Q000188:drug therapy; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D051379:Mice; D008811:Mice, Inbred DBA; D009942:Organometallic Compounds / Q000494:pharmacology*; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*
D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D009942:Organometallic Compounds; C476530:tricarbonylchloro(glycinato)ruthenium(II); D019386:Alendronate