Ajou University repository

Kalkitoxin reduces osteoclast formation and resorption and protects against inflammatory bone lossoa mark
  • Li, Liang ;
  • Yang, Ming ;
  • Shrestha, Saroj Kumar ;
  • Kim, Hyoungsu ;
  • Gerwick, William H. ;
  • Soh, Yunjo
Citations

SCOPUS

0

Citation Export

Publication Year
2021-03-01
Journal
International Journal of Molecular Sciences
Publisher
MDPI AG
Citation
International Journal of Molecular Sciences, Vol.22 No.5, pp.1-12
Keyword
Bone lossInflammationKalkitoxinMarine natural productOsteoclast
Mesh Keyword
ActinsAnimalsBone DensityBone ResorptionCathepsin KCell SurvivalInflammationJanus KinasesLipidsLipopolysaccharidesLyngbyaMacrophage Colony-Stimulating FactorMacrophagesMaleMAP Kinase Signaling SystemMatrix Metalloproteinase 9Membrane ProteinsMiceMice, Inbred ICRNerve Tissue ProteinsNFATC Transcription FactorsOsteoclastsOsteogenesisPhosphorylationProto-Oncogene Proteins c-fosRANK LigandTartrate-Resistant Acid PhosphataseThiazoles
All Science Classification Codes (ASJC)
CatalysisMolecular BiologySpectroscopyComputer Science ApplicationsPhysical and Theoretical ChemistryOrganic ChemistryInorganic Chemistry
Abstract
Osteoclasts, bone-specified multinucleated cells produced by monocyte/macrophage, are involved in numerous bone destructive diseases such as arthritis, osteoporosis, and inflamma-tion-induced bone loss. The osteoclast differentiation mechanism suggests a possible strategy to treat bone diseases. In this regard, we recently examined the in vivo impact of kalkitoxin (KT), a marine product obtained from the marine cyanobacterium Moorena producens (previously Lyngbya majuscula), on the macrophage colony-stimulating factor (M-CSF) and on the receptor activator of nuclear factor κB ligand (RANKL)-stimulated in vitro osteoclastogenesis and inflamma-tion-mediated bone loss. We have now examined the molecular mechanism of KT in greater detail. KT decreased RANKL-induced bone marrow-derived macrophages (BMMs) tartrate-resistant acid phosphatase (TRAP)-multinucleated cells at a late stage. Likewise, KT suppressed RANKL-induced pit area and actin ring formation in BMM cells. Additionally, KT inhibited several RANKL-induced genes such as cathepsin K, matrix metalloproteinase (MMP-9), TRAP, and dendritic cell-specific transmembrane protein (DC-STAMP). In line with these results, RANKL stimulated both genes and protein expression of c-Fos and nuclear factor of activated T cells (NFATc1), and this was also suppressed by KT. Moreover, KT markedly decreased RANKL-induced p-ERK1/2 and p-JNK pathways at different time points. As a result, KT prevented inflammatory bone loss in mice, such as bone mineral density (BMD) and osteoclast differentiation markers. These experiments demonstrated that KT markedly inhibited osteoclast formation and inflammatory bone loss through NFATc1 and mitogen-activated protein kinase (MAPK) signaling pathways. Therefore, KT may have potential as a treatment for destructive bone diseases.
ISSN
1422-0067
Language
eng
URI
https://aurora.ajou.ac.kr/handle/2018.oak/31868
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85101419614&origin=inward
DOI
https://doi.org/2-s2.0-85101419614
Journal URL
https://www.mdpi.com/1422-0067/22/5/2303/pdf
Type
Article
Funding
The Basic Science Research Program supported this research through the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT, and Future Planning (2017R1A2B4011988) and NRF-2017R1A2B4006110.Funding: The Basic Science Research Program supported this research through the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT, and Future Planning (2017R1A2B4011988) and NRF-2017R1A2B4006110.
Show full item record

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Related Researcher

Kim, Hyoungsu Image
Kim, Hyoungsu김형수
Division of Pharmacy Sciences
Read More

Total Views & Downloads

File Download

  • There are no files associated with this item.