1. Bone-targeted methotrexate-alendronate conjugate inhibits osteoclastogenesis in vitro and prevents bone loss and inflammation of collagen-induced arthritis in vivo.
- Author
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Xie Z, Liu G, Tang P, Sun X, Chen S, Qin A, Zhu P, Zhang J, and Fan S
- Subjects
- Animals, Arthritis, Experimental chemically induced, Arthritis, Experimental metabolism, Arthritis, Rheumatoid chemically induced, Arthritis, Rheumatoid drug therapy, Bone Resorption metabolism, Bone and Bones metabolism, Collagen pharmacology, Cytokines metabolism, Drug Therapy, Combination methods, Female, Inflammation metabolism, Male, Mice, Mice, Inbred C57BL, Muramidase metabolism, Osteoclasts drug effects, Osteoclasts metabolism, Rats, Rats, Wistar, Alendronate pharmacology, Arthritis, Experimental drug therapy, Bone Resorption prevention & control, Bone and Bones drug effects, Inflammation drug therapy, Methotrexate pharmacology, Osteogenesis drug effects
- Abstract
Rheumatoid arthritis (RA), a disease that causes joint destruction and bone erosion, is related to osteoclast activity. RA is generally treated with methotrexate (MTX). In this study, a MTX-Alendronate (ALN) conjugate was synthesized and characterized. The conjugate dramatically inhibited osteoclast formation and bone resorption compared with MTX and ALN used alone or in combination. Due to the characteristics of ALN, the MTX-ALN conjugate can adhere to the exposed bone surface and enhance drug accumulation in the pathological region for targeted therapy against osteoclastogenesis. Additionally, MTX was rapidly released in the presence of lysozyme under mildly acidic conditions, similar to inflammatory tissue and osteoclast-surviving conditions, which contributes to inflammatory inhibition; this was confirmed by the presence of pro-inflammatory cytokines. Our study highlights the use of the MTX-ALN conjugate as a potential therapeutic approach for RA by targeting osteoclastogenesis.
- Published
- 2018
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