Effects of the Cathepsin K Inhibitor ONO-5334 and Concomitant Use of ONO-5334 with Methotrexate on Collagen-Induced Arthritis in Cynomolgus Monkeys
المؤلفون المشاركون
Tanaka, Makoto
Yamada, Hiroyuki
Nishikawa, Satoshi
Mori, Hiroshi
Ochi, Yasuo
Nakanishi, Yasutomo
Hashimoto, Yasuaki
Kawabata, Kazuhito
المصدر
International Journal of Rheumatology
العدد
المجلد 2019، العدد 2019 (31 ديسمبر/كانون الأول 2019)، ص ص. 1-9، 9ص.
الناشر
Hindawi Publishing Corporation
تاريخ النشر
2019-02-17
دولة النشر
مصر
عدد الصفحات
9
التخصصات الرئيسية
الملخص EN
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.
نمط استشهاد جمعية علماء النفس الأمريكية (APA)
Yamada, Hiroyuki& Mori, Hiroshi& Nakanishi, Yasutomo& Nishikawa, Satoshi& Hashimoto, Yasuaki& Ochi, Yasuo…[et al.]. 2019. Effects of the Cathepsin K Inhibitor ONO-5334 and Concomitant Use of ONO-5334 with Methotrexate on Collagen-Induced Arthritis in Cynomolgus Monkeys. International Journal of Rheumatology،Vol. 2019, no. 2019, pp.1-9.
https://search.emarefa.net/detail/BIM-1168464
نمط استشهاد الجمعية الأمريكية للغات الحديثة (MLA)
Yamada, Hiroyuki…[et al.]. Effects of the Cathepsin K Inhibitor ONO-5334 and Concomitant Use of ONO-5334 with Methotrexate on Collagen-Induced Arthritis in Cynomolgus Monkeys. International Journal of Rheumatology No. 2019 (2019), pp.1-9.
https://search.emarefa.net/detail/BIM-1168464
نمط استشهاد الجمعية الطبية الأمريكية (AMA)
Yamada, Hiroyuki& Mori, Hiroshi& Nakanishi, Yasutomo& Nishikawa, Satoshi& Hashimoto, Yasuaki& Ochi, Yasuo…[et al.]. Effects of the Cathepsin K Inhibitor ONO-5334 and Concomitant Use of ONO-5334 with Methotrexate on Collagen-Induced Arthritis in Cynomolgus Monkeys. International Journal of Rheumatology. 2019. Vol. 2019, no. 2019, pp.1-9.
https://search.emarefa.net/detail/BIM-1168464
نوع البيانات
مقالات
لغة النص
الإنجليزية
الملاحظات
Includes bibliographical references
رقم السجل
BIM-1168464
قاعدة معامل التأثير والاستشهادات المرجعية العربي "ارسيف Arcif"
أضخم قاعدة بيانات عربية للاستشهادات المرجعية للمجلات العلمية المحكمة الصادرة في العالم العربي
تقوم هذه الخدمة بالتحقق من التشابه أو الانتحال في الأبحاث والمقالات العلمية والأطروحات الجامعية والكتب والأبحاث باللغة العربية، وتحديد درجة التشابه أو أصالة الأعمال البحثية وحماية ملكيتها الفكرية. تعرف اكثر