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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 저널정보
- 대한약리학회 The Korean Journal of Physiology & Pharmacology The Korean Journal of Physiology & Pharmacology 제23권 제1호
- 발행연도
- 2019.1
- 수록면
- 47 - 54 (8page)
이용수
초록· 키워드
오류제보하기
Estrogen withdrawal in post-menopausal women leads to overactivation of osteoclasts, which contributes to the development of osteoporosis. Inflammatory cytokines are known as one of mechanisms of osteoclast activation after estrogen deficiency. SPA0355 is a thiourea derivative that has been investigated for its antioxidant and anti-inflammatory activities. However, its efficacy in bone resorption has not been previously investigated. The aim of this study was to investigate the impact of SPA0355 on the development of osteoporosis and to explore its mode of action. In vitro experiments showed that SPA0355 inhibited receptor activator of NF- B ligand (RANKL)-induced osteoclastogenesis in primary bone marrow-derived macrophages. This effect appears to be independent of estrogen receptor activation as ICI 180,782 failed to abrogate its effects on osteoclasts. Further signaling studies revealed that SPA0355 suppressed activation of the MAPKs, Akt, and NF- B pathways. SPA0355 also increased osteoblastic differentiation, as evidenced by its effects on alkaline phosphatase activity and mineralization nodule formation. Intraperitoneal administration of SPA0355 to ovariectomized mice prevented bone loss, as verified by threedimensional images and bone morphometric parameters derived from CT analysis. Noticeably, SPA0355 did not show hepatotoxicity and nephrotoxicity and also had little effect on hematological parameters. Taken together, the results indicate that SPA0355 may protect against bone loss in ovariectomized mice by stimulation of osteoblast differentiation and by inhibition of osteoclast resorption. Therefore, SPA0355 is a safe and potential candidate for management of postmenopausal osteoporosis.
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참고문헌 (18)
참고문헌 신청
Manolagas SC / 2010 / What old means to bone / Trends Endocrinol Metab 21:369~374
Fujiwara Y / 2016 / RANKL(Receptor Activator of NFκB Ligand)produced by osteocytes is required for the increase in B cells and bone loss caused by estrogen deficiency in mice / J Biol Chem 291:24838~24850
Darnay BG / 1999 / Activation of NF-kappaB by RANK requires tumor necrosis factor receptor-associated factor (TRAF) 6 and NF-kappaB-inducing kinase. Identification of a novel TRAF6 interaction motif / J Biol Chem 274:7724~7731
Eghbali-Fatourechi G / 2003 / Role of RANK ligand in mediating increased bone resorption in early postmenopausal women / J Clin Invest 111:1221~1230
Matsumoto M / 2000 / Involvement of p38 mitogen-activated protein kinase signaling pathway in osteoclastogenesis mediated by receptor activator of NF-kappa B ligand(RANKL) / J Biol Chem 275:31155~31161
Fujiwara Y / 2016 / RANKL(Receptor Activator of NFκB Ligand)produced by osteocytes is required for the increase in B cells and bone loss caused by estrogen deficiency in mice / J Biol Chem 291:24838~24850
Darnay BG / 1999 / Activation of NF-kappaB by RANK requires tumor necrosis factor receptor-associated factor (TRAF) 6 and NF-kappaB-inducing kinase. Identification of a novel TRAF6 interaction motif / J Biol Chem 274:7724~7731
Eghbali-Fatourechi G / 2003 / Role of RANK ligand in mediating increased bone resorption in early postmenopausal women / J Clin Invest 111:1221~1230
Matsumoto M / 2000 / Involvement of p38 mitogen-activated protein kinase signaling pathway in osteoclastogenesis mediated by receptor activator of NF-kappa B ligand(RANKL) / J Biol Chem 275:31155~31161
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