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

Qiang Guo, Zhen Cao, Bo Wu, Fangxiao Chen, Jennifer Tickner, Ziyi Wang, Heng Qiu, Chao Wang, Kai Chen, Renxiang Tan, Qile Gao, Jiake Xu

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3 Citations (Scopus)

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-B 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-kappa B 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.

Original languageEnglish
Pages (from-to)789-801
Number of pages13
JournalJournal of Cellular Physiology
Volume234
Issue number1
DOIs
Publication statusPublished - Jan 2019

Cite this

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title = "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-B 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-kappa B 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.",
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author = "Qiang Guo and Zhen Cao and Bo Wu and Fangxiao Chen and Jennifer Tickner and Ziyi Wang and Heng Qiu and Chao Wang and Kai Chen and Renxiang Tan and Qile Gao and Jiake Xu",
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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. / Guo, Qiang; Cao, Zhen; Wu, Bo; Chen, Fangxiao; Tickner, Jennifer; Wang, Ziyi; Qiu, Heng; Wang, Chao; Chen, Kai; Tan, Renxiang; Gao, Qile; Xu, Jiake.

In: Journal of Cellular Physiology, Vol. 234, No. 1, 01.2019, p. 789-801.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Modulating calcium-mediated NFATc1 and mitogen-activated protein kinase deactivation underlies the inhibitory effects of kavain on osteoclastogenesis and bone resorption

AU - Guo, Qiang

AU - Cao, Zhen

AU - Wu, Bo

AU - Chen, Fangxiao

AU - Tickner, Jennifer

AU - Wang, Ziyi

AU - Qiu, Heng

AU - Wang, Chao

AU - Chen, Kai

AU - Tan, Renxiang

AU - Gao, Qile

AU - Xu, Jiake

PY - 2019/1

Y1 - 2019/1

N2 - 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-B 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-kappa B 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.

AB - 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-B 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-kappa B 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.

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KW - calcium

KW - kavain

KW - MAPK

KW - osteoclast

KW - TNF-ALPHA

KW - KAPPA-B

KW - INDUCED OSTEOPOROSIS

KW - ESTROGEN DEFICIENCY

KW - DIFFERENTIATION

KW - FACTOR-2

KW - MEDICINE

KW - DRUG

U2 - 10.1002/jcp.26893

DO - 10.1002/jcp.26893

M3 - Article

VL - 234

SP - 789

EP - 801

JO - Journal Cellular Physiology

JF - Journal Cellular Physiology

SN - 0021-9541

IS - 1

ER -