Osthole inhibits osteoclasts formation and bone resorption by regulating NF-κB signaling and NFATc1 activations stimulated by RANKL

Yong Ma, Lining Wang, Suyang Zheng, Jiake Xu, Yalan Pan, Pengcheng Tu, Jie Sun, Yang Guo

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Abstract

Chinese herbal medicine Fructus Cnidii has an outstanding effect on chronic lumbar pain and impotence, also has been used against osteoporosis with high frequency. Yet, the mechanisms of osthole, a derivative of Fructus Cnidii, on osteoclasts remains barely known. In this study, it was found out that osthole (10−6mol/L, 10−5mol/L) had the influence of inhibiting osteoclast formation and bone resorptive activities induced by receptor activator of nuclear factor κB ligand (RANKL), rather than affecting the viability of osteoclast-like cells. Furthermore, osthole could also inhibit the messenger RNA expressions of c-Src, tartrate-resistant acid phosphatase, β3-Integrin, matrix metallopeptidase 9, and cathepsin K. The results of the mechanistic study indicated that osthole regulated the nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) and nuclear factor-κB (NF-κB) activations following the RANKL stimulation. These findings suggested that the inhibitory effects of osthole were associated with restraining the activations of NFATc1 and NF-κB induced by RANKL. Thus osthole can be used as a potential treatment for abnormal bone-resorption related diseases.

Original languageEnglish
Pages (from-to)16052-16061
Number of pages10
JournalJournal of Cellular Biochemistry
Volume120
Issue number9
DOIs
Publication statusPublished - 1 Sep 2019

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NFATC Transcription Factors
Osteoclasts
Bone Resorption
Bone
Chemical activation
Cathepsin K
Herbal Medicine
Metalloproteases
Erectile Dysfunction
Cytoplasmic and Nuclear Receptors
Acid Phosphatase
Osteogenesis
Integrins
Chronic Pain
Osteoporosis
osthol
Cells
Ligands
Derivatives
Messenger RNA

Cite this

Ma, Yong ; Wang, Lining ; Zheng, Suyang ; Xu, Jiake ; Pan, Yalan ; Tu, Pengcheng ; Sun, Jie ; Guo, Yang. / Osthole inhibits osteoclasts formation and bone resorption by regulating NF-κB signaling and NFATc1 activations stimulated by RANKL. In: Journal of Cellular Biochemistry. 2019 ; Vol. 120, No. 9. pp. 16052-16061.
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Osthole inhibits osteoclasts formation and bone resorption by regulating NF-κB signaling and NFATc1 activations stimulated by RANKL. / Ma, Yong; Wang, Lining; Zheng, Suyang; Xu, Jiake; Pan, Yalan; Tu, Pengcheng; Sun, Jie; Guo, Yang.

In: Journal of Cellular Biochemistry, Vol. 120, No. 9, 01.09.2019, p. 16052-16061.

Research output: Contribution to journalArticle

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AU - Ma, Yong

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AU - Zheng, Suyang

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AU - Pan, Yalan

AU - Tu, Pengcheng

AU - Sun, Jie

AU - Guo, Yang

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AB - Chinese herbal medicine Fructus Cnidii has an outstanding effect on chronic lumbar pain and impotence, also has been used against osteoporosis with high frequency. Yet, the mechanisms of osthole, a derivative of Fructus Cnidii, on osteoclasts remains barely known. In this study, it was found out that osthole (10−6mol/L, 10−5mol/L) had the influence of inhibiting osteoclast formation and bone resorptive activities induced by receptor activator of nuclear factor κB ligand (RANKL), rather than affecting the viability of osteoclast-like cells. Furthermore, osthole could also inhibit the messenger RNA expressions of c-Src, tartrate-resistant acid phosphatase, β3-Integrin, matrix metallopeptidase 9, and cathepsin K. The results of the mechanistic study indicated that osthole regulated the nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) and nuclear factor-κB (NF-κB) activations following the RANKL stimulation. These findings suggested that the inhibitory effects of osthole were associated with restraining the activations of NFATc1 and NF-κB induced by RANKL. Thus osthole can be used as a potential treatment for abnormal bone-resorption related diseases.

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