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

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.

journal_name

J Cell Physiol

journal_title

Journal of cellular physiology

authors

Guo Q,Cao Z,Wu B,Chen F,Tickner J,Wang Z,Qiu H,Wang C,Chen K,Tan R,Gao Q,Xu J

doi

10.1002/jcp.26893

subject

Has Abstract

pub_date

2018-01-01 00:00:00

pages

789-801

issue

eissn

0021-9541

issn

1097-4652

journal_volume

234

pub_type

杂志文章

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