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Article

Kalkitoxin Reduces Osteoclast Formation and Resorption and Protects against Inflammatory Bone Loss

1
Department of Dental Pharmacology, School of Dentistry, Jeonbuk National University, Jeonju 54896, Korea
2
Department of Periodontology, School of Dentistry, Jeonbuk National University, Jeon-Ju 561-756, Korea
3
College of Pharmacy, Ajou University, San 5, Woncheon-dong, Youngtong-gu Suwon 443-749, Korea
4
Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, CA 92037, USA
5
Laboratory of Pharmacology, School of Pharmacy, Jeonbuk National University, Jeon-Ju 561-756, Korea
*
Author to whom correspondence should be addressed.
Academic Editors: Chih-Hsin Tang and Giacomina Brunetti
Int. J. Mol. Sci. 2021, 22(5), 2303; https://doi.org/10.3390/ijms22052303
Received: 25 December 2020 / Revised: 19 February 2021 / Accepted: 22 February 2021 / Published: 25 February 2021
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
Osteoclasts, bone-specified multinucleated cells produced by monocyte/macrophage, are involved in numerous bone destructive diseases such as arthritis, osteoporosis, and inflammation-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 inflammation-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. View Full-Text
Keywords: kalkitoxin; marine natural product; osteoclast; inflammation; bone loss kalkitoxin; marine natural product; osteoclast; inflammation; bone loss
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MDPI and ACS Style

Li, L.; Yang, M.; Shrestha, S.K.; Kim, H.; Gerwick, W.H.; Soh, Y. Kalkitoxin Reduces Osteoclast Formation and Resorption and Protects against Inflammatory Bone Loss. Int. J. Mol. Sci. 2021, 22, 2303. https://doi.org/10.3390/ijms22052303

AMA Style

Li L, Yang M, Shrestha SK, Kim H, Gerwick WH, Soh Y. Kalkitoxin Reduces Osteoclast Formation and Resorption and Protects against Inflammatory Bone Loss. International Journal of Molecular Sciences. 2021; 22(5):2303. https://doi.org/10.3390/ijms22052303

Chicago/Turabian Style

Li, Liang, Ming Yang, Saroj K. Shrestha, Hyoungsu Kim, William H. Gerwick, and Yunjo Soh. 2021. "Kalkitoxin Reduces Osteoclast Formation and Resorption and Protects against Inflammatory Bone Loss" International Journal of Molecular Sciences 22, no. 5: 2303. https://doi.org/10.3390/ijms22052303

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