{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T22:50:23Z","timestamp":1782514223652,"version":"3.54.5"},"reference-count":35,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2016,10,10]],"date-time":"2016-10-10T00:00:00Z","timestamp":1476057600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"The National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81472122"],"award-info":[{"award-number":["81472122"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Natural Science Foundation of Guangdong Province, China","award":["2014A030310109"],"award-info":[{"award-number":["2014A030310109"]}]},{"name":"Guangzhou Science and Technology Project","award":["201510010049"],"award-info":[{"award-number":["201510010049"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteoporosis and Alzheimer\u2019s disease (AD) are common chronic degenerative disorders which are strongly associated with advanced age. We have previously demonstrated that amyloid beta peptide (A\u03b2), one of the pathological hallmarks of AD, accumulated abnormally in osteoporotic bone specimens in addition to having an activation effect on osteoclast (Bone 2014,61:164-75). However, the underlying molecular mechanisms remain unclear. Activation of NF-\u03baB, extracellular signal-regulated kinase (ERK) phosphorylates, and calcium oscillation signaling pathways by receptor activator NF-\u03baB ligand (RANKL) plays a pivotal role in osteoclast activation. Targeting this signaling to modulate osteoclast function has been a promising strategy for osteoclast-related diseases. In this study, we investigated the effects of A\u03b2 on RANKL-induced osteoclast signaling pathways in vitro. In mouse bone marrow monocytes (BMMs), A\u03b2 exerted no effect on RANKL-induced osteoclastogenesis but promoted osteoclastic bone resorption. In molecular levels, A\u03b2 enhanced NF-\u03baB activity and I\u03baB-\u03b1 degradation, activated ERK phosphorylation and stimulated calcium oscillation, thus leading to upregulation of NFAT-c1 expression during osteoclast activation. Taken together, our data demonstrate that A\u03b2 enhances RANKL-induced osteoclast activation through I\u03baB-\u03b1 degradation, ERK phosphorylation, and calcium oscillation signaling pathways and that A\u03b2 may be a promising agent in the treatment of osteoclast-related disease such as osteoporosis.<\/jats:p>","DOI":"10.3390\/ijms17101683","type":"journal-article","created":{"date-parts":[[2016,10,10]],"date-time":"2016-10-10T10:35:19Z","timestamp":1476095719000},"page":"1683","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Amyloid \u03b2 Peptide Enhances RANKL-Induced Osteoclast Activation through NF-\u03baB, ERK, and Calcium Oscillation Signaling"],"prefix":"10.3390","volume":"17","author":[{"given":"Shangfu","family":"Li","sequence":"first","affiliation":[{"name":"Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen University, TianHe Road 600, TianHe District, Guangzhou 510630, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen University, TianHe Road 600, TianHe District, Guangzhou 510630, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dian","family":"Teguh","sequence":"additional","affiliation":[{"name":"Molecular Lab, School of Pathology and Laboratory Medicine, University of Western Australia, Perth 6009, WA, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Molecular Lab, School of Pathology and Laboratory Medicine, University of Western Australia, Perth 6009, WA, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiake","family":"Xu","sequence":"additional","affiliation":[{"name":"Molecular Lab, School of Pathology and Laboratory Medicine, University of Western Australia, Perth 6009, WA, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limin","family":"Rong","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen University, TianHe Road 600, TianHe District, Guangzhou 510630, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,10,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.jtemb.2014.08.010","article-title":"Osteoporosis in neurodegeneration","volume":"28","author":"Roos","year":"2014","journal-title":"J. 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