A novel pyrazole derivative protects from ovariectomy-induced osteoporosis through the inhibition of NADPH oxidase
DC Field | Value | Language |
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dc.contributor.author | Joo, Jung Hee | - |
dc.contributor.author | Huh, Jeong-Eun | - |
dc.contributor.author | Lee, Jee Hyun | - |
dc.contributor.author | Park, Doo Ri | - |
dc.contributor.author | Lee, Yoonji | - |
dc.contributor.author | Lee, Seul Gee | - |
dc.contributor.author | Choi, Sun | - |
dc.contributor.author | Lee, Hwa Jeong | - |
dc.contributor.author | Song, Seong-Won | - |
dc.contributor.author | Jeong, Yongmi | - |
dc.contributor.author | Goo, Ja-Il | - |
dc.contributor.author | Choi, Yongseok | - |
dc.contributor.author | Baek, Hye Kyung | - |
dc.contributor.author | Yi, Sun Shin | - |
dc.contributor.author | Park, Soo Jin | - |
dc.contributor.author | Lee, Ji Eun | - |
dc.contributor.author | Ku, Sae Kwang | - |
dc.contributor.author | Lee, Won Jae | - |
dc.contributor.author | Lee, Kee-In | - |
dc.contributor.author | Lee, Soo Young | - |
dc.contributor.author | Bae, Yun Soo | - |
dc.date.accessioned | 2021-09-04T01:31:15Z | - |
dc.date.available | 2021-09-04T01:31:15Z | - |
dc.date.created | 2021-06-17 | - |
dc.date.issued | 2016-03-15 | - |
dc.identifier.issn | 2045-2322 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/89205 | - |
dc.description.abstract | Osteoclast cells (OCs) are differentiated from bone marrow-derived macrophages (BMMs) by activation of receptor activator of nuclear factor kappa B (NF-kappa B) ligand (RANKL). Activation of NADPH oxidase (Nox) isozymes is involved in RANKL-dependent OC differentiation, implicating Nox isozymes as therapeutic targets for treatment of osteoporosis. Here, we show that a novel pyrazole derivative, Ewha-18278 has high inhibitory potency on Nox isozymes. Blocking the activity of Nox with Ewha-18278 inhibited the responses of BMMs to RANKL, including reactive oxygen species (ROS) generation, activation of mitogen-activated protein (MAP) kinases and NF-kappa B, and OC differentiation. To evaluate the anti-osteoporotic function of Ewha-18278, the derivative was applied to estrogen-deficient ovariectomized (OVX) ddY mice. Oral administration of Ewha-18278 (10 mg/kg/daily, 4 weeks) into the mice recovered bone mineral density, trabecular bone volume, trabecular bone length, number and thickness, compared to control OVX ddY mice. Moreover, treatment of OVX ddY mice with Ewha-18278 increased bone strength by increasing cortical bone thickness. We provide that Ewha-18278 displayed Nox inhibition and blocked the RANKL-dependent cell signaling cascade leading to reduced differentiation of OCs. Our results implicate Ewha-18278 as a novel therapeutic agent for the treatment of osteoporosis. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.subject | DEFICIENCY BONE LOSS | - |
dc.subject | POSTMENOPAUSAL OSTEOPOROSIS | - |
dc.subject | REACTIVE OXYGEN | - |
dc.subject | OSTEOCLAST DIFFERENTIATION | - |
dc.subject | HYDROGEN-PEROXIDE | - |
dc.subject | OXIDATIVE STRESS | - |
dc.subject | CRUCIAL ROLE | - |
dc.subject | MICE | - |
dc.subject | RISEDRONATE | - |
dc.subject | DISEASE | - |
dc.title | A novel pyrazole derivative protects from ovariectomy-induced osteoporosis through the inhibition of NADPH oxidase | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Choi, Yongseok | - |
dc.identifier.doi | 10.1038/srep22389 | - |
dc.identifier.scopusid | 2-s2.0-84960947591 | - |
dc.identifier.wosid | 000372028100001 | - |
dc.identifier.bibliographicCitation | SCIENTIFIC REPORTS, v.6 | - |
dc.relation.isPartOf | SCIENTIFIC REPORTS | - |
dc.citation.title | SCIENTIFIC REPORTS | - |
dc.citation.volume | 6 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.subject.keywordPlus | DEFICIENCY BONE LOSS | - |
dc.subject.keywordPlus | POSTMENOPAUSAL OSTEOPOROSIS | - |
dc.subject.keywordPlus | REACTIVE OXYGEN | - |
dc.subject.keywordPlus | OSTEOCLAST DIFFERENTIATION | - |
dc.subject.keywordPlus | HYDROGEN-PEROXIDE | - |
dc.subject.keywordPlus | OXIDATIVE STRESS | - |
dc.subject.keywordPlus | CRUCIAL ROLE | - |
dc.subject.keywordPlus | MICE | - |
dc.subject.keywordPlus | RISEDRONATE | - |
dc.subject.keywordPlus | DISEASE | - |
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