1. Ruboxistaurin maintains the bone mass of subchondral bone for blunting osteoarthritis progression by inhibition of osteoclastogenesis and bone resorption activity.
- Author
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Pang C, Wen L, Lu X, Luo S, Qin H, Zhang X, Zhu B, and Luo S
- Subjects
- Animals, Bone Density physiology, Bone Remodeling physiology, Bone Resorption metabolism, Bone Resorption pathology, Cells, Cultured, Disease Progression, Dose-Response Relationship, Drug, Enzyme Inhibitors pharmacology, Enzyme Inhibitors therapeutic use, Female, Femur drug effects, Femur metabolism, Femur pathology, Indoles pharmacology, Male, Maleimides pharmacology, Mice, Mice, Inbred C57BL, Osteoarthritis metabolism, Osteoarthritis pathology, Osteoclasts metabolism, Osteoclasts pathology, Osteogenesis drug effects, Osteogenesis physiology, Bone Density drug effects, Bone Remodeling drug effects, Bone Resorption prevention & control, Indoles therapeutic use, Maleimides therapeutic use, Osteoarthritis prevention & control, Osteoclasts drug effects
- Abstract
Osteoarthritis (OA) is a common degenerative disease with a series of changes occurring in aging cartilage, such as increased oxidative stress, decreased markers of healthy cartilage and alterations in the autophagy pathway. And increasing evidence indicates that osteoarthritis affects the whole joint, including both cartilage and subchondral bone. The agents that can effectively suppress chondrocyte degradation and subchondral bone deterioration are crucial for the prevention and treatment of OA. Ruboxistaurin (RU), an orally active protein kinase C inhibitor, can reduce macrophage adhesion to endothelial cells and relieve the local inflammation when applicating in diabetes and kinds of aging-related vasculopathy, which were realized by its effects on decreasing inflammatory cytokines' expression and increasing cell anti-oxidative stress ability. However, whether ruboxistaurin protects against OA remains unknown. In this study, we investigated the therapeutic effects of ruboxistaurin in an anterior cruciate ligament transection (ACLT)-induced OA model by preventing the bone mass loss of subchondral bone. We found that ruboxistaurin can effectively alleviate ACLT-induced osteoarthritis, as demonstrated by the phenomenon of correcting pathological bone loss caused by osteoclasts overactivated in the early stage of osteoarthritis and protecting against articular cartilage degeneration. Moreover, we found that ruboxistaurin inhibited osteoclast formation and resorption activity by suppressing the expressions of osteoclast-related genes and (PKCδ/MAPKs) signaling cascade. Taken together, these results show that ruboxistaurin may be a potential therapeutic agent for rescuing abnormal subchondral bone deterioration and cartilage degradation in OA and reverses the vicious cycle related to osteoarthritis., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
- Published
- 2020
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