Randomized controlled studies on the efficacy of antiarthritic agents in inhibiting cartilage degeneration and pain associated with progression of osteoarthritis in the rat

Arthritis Research & Therapy
Erica M TenBroekA M Bendele

Abstract

As an initial step in the development of a local therapeutic to treat osteoarthritis (OA), a number of agents were tested for their ability to block activation of inflammation through nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), subchondral bone changes through receptor activator of nuclear factor κB ligand (RANKL)-mediated osteoclastogenesis, and proteolytic degradation through matrix metalloproteinase (MMP)-13 activity. Candidates with low toxicity and predicted efficacy were further examined using either of two widely accepted models of OA joint degeneration in the rat: the monoiodoacetic acid (MIA) model or the medial meniscal tear/medial collateral ligament tear (MMT/MCLT) model. Potential therapeutics were assessed for their effects on the activation of nuclear factor (NF)-κB, RANKL-mediated osteoclastogenesis, and MMP-13 activity in vitro using previously established assays. Toxicity was measured using HeLa cells, a synovial cell line, or primary human chondrocytes. Drugs predicted to perform well in vivo were tested either systemically or via intraarticular injection in the MIA or the MMT/MCLT model of OA. Pain behavior was measured by mechanical hyperalgesia using the digital Randall-Selitto test...Continue Reading

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Citations

Dec 10, 2019·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Kelly A KimmerlingKatie C Mowry
Oct 3, 2019·Expert Review of Clinical Pharmacology·T M SaffariC A Hundepool
Feb 1, 2017·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·William KingJennifer Woodell-May
Jun 20, 2018·Frontiers in Endocrinology·Holly L RacineMaria A Serrat
Jan 13, 2021·PloS One·Lyvia Maria Rodrigues de Sousa GomesJoão Batista Santos Garcia
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May 1, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Stanislav SukhikhOlga Babich
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ishtiaq AhmedQingyou Liu
Jul 29, 2021·Nature Reviews. Rheumatology·Karen ChingChunyi Wen
Jul 19, 2021·Clinical and Experimental Pharmacology & Physiology·Felicity Y HanMaree T Smith

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Methods Mentioned

BETA
Assay
enzyme-linked immunosorbent assay
lavage

Software Mentioned

biomedical
Prism
MS Excel
GraphPad

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