Modulating calcium-mediated NFATc1 and mitogen-activated protein kinase deactivation underlies the inhibitory effects of kavain on osteoclastogenesis and bone resorption

11Citations
Citations of this article
21Readers
Mendeley users who have this article in their library.

Abstract

Osteoclasts are responsible for bone resorption during the process of bone remodeling. Increased osteoclast numbers and bone resorption activity are the main factors contributing to bone loss–related diseases such as osteoporosis. Therefore, modulating the formation and function of osteoclasts is critical for the effective treatment of osteolysis and osteoporosis. Kavain is the active ingredient extracted from the root of the kava plant, which possesses known anti-inflammatory properties. However, the effects of kavain on osteoclastogenesis and bone resorption remain unclear. In this study, we found that kavain inhibits receptor activator of nuclear factor-κB ligand (RANKL)–induced osteoclast differentiation and fusion using tartrate-resistant acid phosphatase staining and immunofluorescence. Furthermore, kavain inhibited bone resorption performed by osteoclasts. Using reverse transcription-polymerase chain reaction and western blot analysis, we found that kavain downregulates the expression of osteoclast marker genes, such as nuclear factor of activated T cells, cytoplasmic 1 (Nfatc1), v-atpase d2 (Atp6v0d2), dendrocyte expressed seven transmembrane protein (Dcstamp), matrix metallopeptidase 9 (Mmp9), cathepsin K (Ctsk), and Acp5. Additionally, kavain repressed RANKL-induced calcium oscillations, nuclear factor of activated T cells activation, and mitogen-activated protein kinase phosphorylation, while leaving NF-κB unaffected. We found no effects of kavain on either osteoblast proliferation or differentiation. Besides, kavain inhibited bone loss in ovariectomized mice by suppressing osteoclastogenesis. Collectively, these data suggest a potential use for kavain as a candidate drug for the treatment of osteolytic diseases.

References Powered by Scopus

Osteoclast differentiation and activation

5559Citations
N/AReaders
Get full text

Osteoporosis: Now and the future

2181Citations
N/AReaders
Get full text

RANKL-RANK signaling in osteoclastogenesis and bone disease

1009Citations
N/AReaders
Get full text

Cited by Powered by Scopus

CircRNA_28313/miR-195a/CSF1 axis modulates osteoclast differentiation to affect OVX-induced bone absorption in mice

111Citations
N/AReaders
Get full text

The role of bmp signaling in osteoclast regulation

27Citations
N/AReaders
Get full text

A Review on the Molecular Mechanisms of Action of Natural Products in Preventing Bone Diseases

21Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Guo, Q., Cao, Z., Wu, B., Chen, F., Tickner, J., Wang, Z., … Xu, J. (2018). Modulating calcium-mediated NFATc1 and mitogen-activated protein kinase deactivation underlies the inhibitory effects of kavain on osteoclastogenesis and bone resorption. Journal of Cellular Physiology, 234(1), 789–801. https://doi.org/10.1002/jcp.26893

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 6

75%

Lecturer / Post doc 2

25%

Readers' Discipline

Tooltip

Medicine and Dentistry 5

63%

Pharmacology, Toxicology and Pharmaceut... 1

13%

Chemistry 1

13%

Earth and Planetary Sciences 1

13%

Save time finding and organizing research with Mendeley

Sign up for free