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The current study describes for the first time that HAR inhibits receptor activator of nuclear factor \u03baB ligand (RANKL)-induced osteoclastogenesis in vitro and suppresses inflammation-induced bone loss in a mouse model. HAR also inhibited the formation of osteoclasts from mouse bone marrow macrophages (BMMs) in a dose-dependent manner as well as the activity of mature osteoclasts, including filamentous actin (F-actin) ring formation and bone matrix breakdown. This involved a HAR-induced decrease in extracellular signal-regulated kinase (ERK) and c-jun N-terminal kinase (JNK) phosphorylation, leading to the inhibition of Syk-Btk-PLC\u03b32-Ca2+ in RANKL-dependent early signaling, as well as the activation of c-Fos and nuclear factor of activated T cells cytoplasmic 1 (NFATc1), which resulted in the down-regulation of various target genes. Consistent with these in vitro results, HAR blocked lipopolysaccharide (LPS)-induced bone loss in an inflammatory osteoporosis model. However, HAR did not prevent ovariectomy-mediated bone erosion in a postmenopausal osteoporosis model. These results suggest that HAR is a valuable agent against inflammation-related bone disorders but not osteoporosis induced by hormonal abnormalities.<\/jats:p>","DOI":"10.1021\/acs.jnatprod.5b00233","type":"journal-article","created":{"date-parts":[[2015,8,26]],"date-time":"2015-08-26T10:34:18Z","timestamp":1440585258000},"page":"2167-2174","source":"Crossref","is-referenced-by-count":40,"title":["Harpagoside Inhibits RANKL-Induced Osteoclastogenesis\nvia Syk-Btk-PLC\u03b32-Ca2+ Signaling Pathway and Prevents\nInflammation-Mediated Bone Loss"],"prefix":"10.1021","volume":"78","author":[{"given":"Ju-Young","family":"Kim","sequence":"first","affiliation":[{"name":"Wonkwang University , , , , , , ,","place":["Iksan, Jeonbuk, Korea, 570-749"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun-Hyang","family":"Park","sequence":"additional","affiliation":[{"name":"Wonkwang University , , , , , , ,","place":["Iksan, Jeonbuk, Korea, 570-749"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong Min","family":"Baek","sequence":"additional","affiliation":[{"name":"Wonkwang University , , , , , , ,","place":["Iksan, Jeonbuk, Korea, 570-749"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munkhsoyol","family":"Erkhembaatar","sequence":"additional","affiliation":[{"name":"Wonkwang University , , , , , , ,","place":["Iksan, Jeonbuk, Korea, 570-749"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Seuk","family":"Kim","sequence":"additional","affiliation":[{"name":"Wonkwang University , , , , , , ,","place":["Iksan, Jeonbuk, Korea, 570-749"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwon-Ha","family":"Yoon","sequence":"additional","affiliation":[{"name":"Wonkwang University , , , , , , ,","place":["Iksan, Jeonbuk, Korea, 570-749"]},{"name":"Wonkwang University , , , , , , ,","place":["Iksan, Jeonbuk, Korea, 570-749"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaemin","family":"Oh","sequence":"additional","affiliation":[{"name":"Wonkwang University , , , , , , ,","place":["Iksan, Jeonbuk, Korea, 570-749"]},{"name":"Wonkwang University , , , , , , ,","place":["Iksan, Jeonbuk, Korea, 570-749"]},{"name":"Wonkwang University , , , , , , ,","place":["Iksan, Jeonbuk, Korea, 570-749"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myeung Su","family":"Lee","sequence":"additional","affiliation":[{"name":"Wonkwang University , , , , , , ,","place":["Iksan, Jeonbuk, Korea, 570-749"]},{"name":"Wonkwang University , , , , , , ,","place":["Iksan, Jeonbuk, Korea, 570-749"]},{"name":"Wonkwang University , , , , , , ,","place":["Iksan, Jeonbuk, Korea, 570-749"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2015,8,26]]},"reference":[{"key":"2026090222293266300_cit1","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1093\/gerona\/glt093","volume":"68","author":"Cauley","year":"2013","journal-title":"J. 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