Effects of the Cathepsin K Inhibitor ONO-5334 and Concomitant Use of ONO-5334 with Methotrexate on Collagen-Induced Arthritis in Cynomolgus Monkeys.

IF 2.3 Q2 RHEUMATOLOGY International Journal of Rheumatology Pub Date : 2019-02-17 eCollection Date: 2019-01-01 DOI:10.1155/2019/5710340
Hiroyuki Yamada, Hiroshi Mori, Yasutomo Nakanishi, Satoshi Nishikawa, Yasuaki Hashimoto, Yasuo Ochi, Makoto Tanaka, Kazuhito Kawabata
{"title":"Effects of the Cathepsin K Inhibitor ONO-5334 and Concomitant Use of ONO-5334 with Methotrexate on Collagen-Induced Arthritis in Cynomolgus Monkeys.","authors":"Hiroyuki Yamada,&nbsp;Hiroshi Mori,&nbsp;Yasutomo Nakanishi,&nbsp;Satoshi Nishikawa,&nbsp;Yasuaki Hashimoto,&nbsp;Yasuo Ochi,&nbsp;Makoto Tanaka,&nbsp;Kazuhito Kawabata","doi":"10.1155/2019/5710340","DOIUrl":null,"url":null,"abstract":"<p><p>We examined whether the cathepsin K inhibitor, ONO-5334, administered alone or in combination with methotrexate (MTX), could ameliorate joint destruction evoked by collagen-induced arthritis (CIA) in female cynomolgus monkeys. CIA was induced by immunizing with bovine type II collagen. ONO-5334 (30 mg/kg/day) was orally administered once daily and MTX (10 mg/body/day) twice weekly for 9 weeks. X-ray (evaluation of joint destruction) and swelling (inflammatory) scores of proximal interphalangeal (PIP), distal interphalangeal (DIP), and metacarpophalangeal (MP) joints were evaluated. Urinary concentrations of C-terminal telopeptide of type I collagen (CTX-I) and type II collagen (CTX-II) were measured. Arthritis, accompanied by bone and cartilage destruction, was successfully induced in this collagen-induced arthritis monkey model. ONO-5334 showed no suppressive effect on joint swelling, while the joint swelling scores in the MTX and combination (ONO-5334 + MTX) groups were less than 50% compared with the control group. ONO-5334 decreased X-ray score by a mean of 64% (p<0.05 vs the control group), and MTX also decreased in X-ray score by a mean of 46% but with no statistical significance. Combination of ONO-5334 and MTX further decreased the X-ray score by 28% over MTX group (74% reduction vs the control group, p<0.01). Maximum increase in CTX-I (10-fold) and CTX-II (7-fold) compared to baseline was observed at 7 and 3 weeks after the first sensitization, respectively. After treatment with ONO-5334 alone or in combination with MTX, concentrations were maintained near baseline for both markers. In conclusion, ONO-5334 prevented joint destruction but not joint inflammation in this monkey CIA model. Concomitant use of ONO-5334 with MTX reduced architectural joint destruction compared to MTX alone; therefore, ONO-5334 may help to prevent joint destruction in combination with MTX for the treatment of rheumatoid arthritis.</p>","PeriodicalId":51715,"journal":{"name":"International Journal of Rheumatology","volume":null,"pages":null},"PeriodicalIF":2.3000,"publicationDate":"2019-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2019/5710340","citationCount":"10","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Rheumatology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1155/2019/5710340","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2019/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
引用次数: 10

Abstract

We examined whether the cathepsin K inhibitor, ONO-5334, administered alone or in combination with methotrexate (MTX), could ameliorate joint destruction evoked by collagen-induced arthritis (CIA) in female cynomolgus monkeys. CIA was induced by immunizing with bovine type II collagen. ONO-5334 (30 mg/kg/day) was orally administered once daily and MTX (10 mg/body/day) twice weekly for 9 weeks. X-ray (evaluation of joint destruction) and swelling (inflammatory) scores of proximal interphalangeal (PIP), distal interphalangeal (DIP), and metacarpophalangeal (MP) joints were evaluated. Urinary concentrations of C-terminal telopeptide of type I collagen (CTX-I) and type II collagen (CTX-II) were measured. Arthritis, accompanied by bone and cartilage destruction, was successfully induced in this collagen-induced arthritis monkey model. ONO-5334 showed no suppressive effect on joint swelling, while the joint swelling scores in the MTX and combination (ONO-5334 + MTX) groups were less than 50% compared with the control group. ONO-5334 decreased X-ray score by a mean of 64% (p<0.05 vs the control group), and MTX also decreased in X-ray score by a mean of 46% but with no statistical significance. Combination of ONO-5334 and MTX further decreased the X-ray score by 28% over MTX group (74% reduction vs the control group, p<0.01). Maximum increase in CTX-I (10-fold) and CTX-II (7-fold) compared to baseline was observed at 7 and 3 weeks after the first sensitization, respectively. After treatment with ONO-5334 alone or in combination with MTX, concentrations were maintained near baseline for both markers. In conclusion, ONO-5334 prevented joint destruction but not joint inflammation in this monkey CIA model. Concomitant use of ONO-5334 with MTX reduced architectural joint destruction compared to MTX alone; therefore, ONO-5334 may help to prevent joint destruction in combination with MTX for the treatment of rheumatoid arthritis.

Abstract Image

Abstract Image

Abstract Image

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
组织蛋白酶K抑制剂ONO-5334及ONO-5334与甲氨蝶呤合用对食蟹猴胶原性关节炎的影响
我们研究了组织蛋白酶K抑制剂ONO-5334单独或与甲氨蝶呤(MTX)联合使用是否可以改善雌性食蟹猴胶原诱导关节炎(CIA)引起的关节破坏。用牛ⅱ型胶原免疫诱导CIA。ONO-5334 (30 mg/kg/天)每日口服一次,MTX (10 mg/体/天)每周两次,共9周。评估近端指间关节(PIP)、远端指间关节(DIP)和掌指关节(MP)的x线(关节破坏评估)和肿胀(炎症)评分。测定尿中I型胶原(CTX-I)和II型胶原(CTX-II) c末端末端肽的浓度。在这种胶原诱导的关节炎猴子模型中,成功地诱导了伴有骨和软骨破坏的关节炎。ONO-5334对关节肿胀无抑制作用,而与对照组相比,MTX和联合用药(ONO-5334 + MTX)组关节肿胀评分均小于50%。ONO-5334使x线评分平均降低64% (p
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
CiteScore
4.40
自引率
0.00%
发文量
9
审稿时长
24 weeks
期刊最新文献
An Observational Study on the Clinical Characteristics and Prognosis of Patients With Interstitial Lung Disease Secondary to Dermatomyositis and Antisynthetase Syndrome. Exploring the Psychiatric Manifestations of Primary Sjögren’s Syndrome: A Narrative Review Association of Baseline Serum Soluble Tumour Necrosis Factor Receptor Levels with the Response of Rheumatoid Arthritis to Janus Kinase Inhibitor Therapy. Primary Immune Thrombocytopenic Purpura (ITP) and ITP Associated with Systemic Lupus Erythematosus: A Review of Clinical Characteristics and Treatment Modalities Association of Cytokine IL-17, IL-4, IL-6, and IL-12 Gene Polymorphisms in Rheumatoid Arthritis Patients in a Tertiary Care Hospital in Bangladesh.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1