Show simple item record

dc.contributor.authorWang, Qingqing
dc.contributor.authorChen, Delong
dc.contributor.authorJin, Haiming
dc.contributor.authorYe, Zhen
dc.contributor.authorWang, Chao
dc.contributor.authorChen, Kai
dc.contributor.authorKuek, Vincent
dc.contributor.authorXu, Ke
dc.contributor.authorQiu, Heng
dc.contributor.authorChen, Peng
dc.contributor.authorSong, Dezhi
dc.contributor.authorZhao, Jinmin
dc.contributor.authorLiu, Qian
dc.contributor.authorDavis, Rohan A
dc.contributor.authorSong, Fangming
dc.contributor.authorXu, Jiake
dc.date.accessioned2020-08-31T04:40:15Z
dc.date.available2020-08-31T04:40:15Z
dc.date.issued2020
dc.identifier.issn0884-0431
dc.identifier.doi10.1002/jbmr.4025
dc.identifier.urihttp://hdl.handle.net/10072/396934
dc.description.abstractExcessive osteoclast (OC) activity together with relatively weak osteoblast (OB) function are strongly connected to osteolytic diseases, including osteoporosis, tumor‐induced osteolysis, and inflammatory bone erosion. Very few natural products or compounds have been shown to exert therapeutic effects on both OCs and OBs, limiting the potential development of natural compounds for clinical application. Hymenialdisine (HMD) is a marine sponge–derived natural inhibitor of protein kinases with previously reported anti‐osteoarthritis and anti‐cancer properties. However, the roles of HMD in OCs, OBs, and osteoporosis have not yet been well established. Here, we found that HMD not only suppressed osteoclastogenesis but also promoted OB differentiation. HMD exerted dose‐dependent inhibitory effects on RANKL‐induced OC formation, bone resorption, and OC‐specific gene expression. These strong inhibitory effects were achieved by blocking the NF‐κB and MAPK signaling pathways, and NFATc1 expression. In addition, HMD potentially stimulated OB differentiation by activating alkaline phosphatase (ALP) and enhancing OB matrix mineralization. We found that HMD can activate the glycogen synthase kinase 3β (GSK‐3β)/β‐catenin/T‐cell factor (TCF)/lymphoid enhancer factor (LEF) signaling pathway to upregulate Runx‐2 expression, the main transcription factor in this pathway. Increased expression of Runx‐2 was also correlated with expression of the OB‐specific genes Col1a1 and osteocalcin (Ocn). Furthermore, we also evaluated the therapeutic potential of HMD in a female C57BL/6j mouse model of ovariectomy (OVX)‐induced systematic bone loss. HMD showed a remarkable ability to prevent decreases in bone volume (BV/TV) and trabecular thickness (Tb.Th). In summary, HMD exerts notable effects in inhibiting OC‐related osteolysis and enhancing OB‐induced ossification, suggesting the potential application of HMD in osteoporosis treatment.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherWiley
dc.relation.ispartofpagefrom1582
dc.relation.ispartofpageto1596
dc.relation.ispartofissue8
dc.relation.ispartofjournalJournal of Bone and Mineral Research
dc.relation.ispartofvolume35
dc.subject.fieldofresearchBiological sciences
dc.subject.fieldofresearchEngineering
dc.subject.fieldofresearchBiomedical and clinical sciences
dc.subject.fieldofresearchcode31
dc.subject.fieldofresearchcode40
dc.subject.fieldofresearchcode32
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsEndocrinology & Metabolism
dc.subject.keywordsOSTEOCLASTS
dc.subject.keywordsOSTEOBLASTS
dc.titleHymenialdisine: A Marine Natural Product That Acts on Both Osteoblasts and Osteoclasts and Prevents Estrogen-Dependent Bone Loss in Mice
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationWang, Q; Chen, D; Jin, H; Ye, Z; Wang, C; Chen, K; Kuek, V; Xu, K; Qiu, H; Chen, P; Song, D; Zhao, J; Liu, Q; Davis, RA; Song, F; Xu, J, Hymenialdisine: A Marine Natural Product That Acts on Both Osteoblasts and Osteoclasts and Prevents Estrogen-Dependent Bone Loss in Mice, Journal of Bone and Mineral Research, 2020, 35 (8)
dcterms.dateAccepted2020-04-02
dc.date.updated2020-08-31T04:38:40Z
gro.hasfulltextNo Full Text
gro.griffith.authorDavis, Rohan A.


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

  • Journal articles
    Contains articles published by Griffith authors in scholarly journals.

Show simple item record