Glechoma hederacea suppresses RANKL-mediated osteoclastogenesis

J. K. Hwang, M. Erkhembaatar, D. R. Gu, S. H. Lee, C. H. Lee, DongMin Shin, Y. R. Lee, M. S. Kim

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Glechoma hederacea (GH), commonly known as ground-ivy or gill-over-theground, has been extensively used in folk remedies for relieving symptoms of inflammatory disorders. However, the molecular mechanisms underlying the therapeutic action of GH are poorly understood. Here, we demonstrate that GH constituents inhibit osteoclastogenesis by abrogating receptor activator of nuclear κ-B ligand (RANKL)-induced free cytosolic Ca2+ ([Ca2+]i) oscillations. To evaluate the effect of GH on osteoclastogenesis, we assessed the formation of multi-nucleated cells (MNCs), enzymatic activity of tartrateresistant acidic phosphatase (TRAP), expression of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), and [Ca 2+]i alterations in response to treatment with GH ethanol extract (GHE) in primarily cultured bone marrow- derived macrophages (BMMs). Treatment of RANKL-stimulated or non-stimulated BMMs with GHE markedly suppressed MNC formation, TRAP activity, and NFATc1 expression in a dose-dependent manner. Additionally, GHE treatment induced a large transient elevation in [Ca 2+]i while suppressing RANKL-induced [Ca2+]i oscillations, which are essential for NFATc1 activation. GHE-evoked increase in [Ca 2+]i was dependent on extracellular Ca2+ and was inhibited by 1,4-dihydropyridine (DHP), inhibitor of voltage-gated Ca2+ channels (VGCCs), but was independent of storeoperated Ca2+ channels. Notably, after transient [Ca2+] elevation, treatment with GHE desensitized the VGCCs, resulting in an abrogation of RANKLinduced [Ca 2+]i oscillations and MNC formation. These findings demonstrate that treatment of BMMs with GHE suppresses RANKL-mediated osteoclastogenesis by activating and then desensitizing DHP-sensitive VGCCs, suggesting potential applications of GH in the treatment of bone disorders, such as periodontitis, osteoporosis, and rheumatoid arthritis.

Original languageEnglish
Pages (from-to)685-690
Number of pages6
JournalJournal of Dental Research
Volume93
Issue number7
DOIs
Publication statusPublished - 2014 Jan 1

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Lamiaceae
Osteogenesis
Ethanol
NFATC Transcription Factors
Macrophages
Phosphoric Monoester Hydrolases
Therapeutics
Periodontitis
Traditional Medicine
Cytoplasmic and Nuclear Receptors
Osteoporosis
Rheumatoid Arthritis
Ligands
Bone and Bones

All Science Journal Classification (ASJC) codes

  • Dentistry(all)

Cite this

Hwang, J. K., Erkhembaatar, M., Gu, D. R., Lee, S. H., Lee, C. H., Shin, D., ... Kim, M. S. (2014). Glechoma hederacea suppresses RANKL-mediated osteoclastogenesis. Journal of Dental Research, 93(7), 685-690. https://doi.org/10.1177/0022034514536579
Hwang, J. K. ; Erkhembaatar, M. ; Gu, D. R. ; Lee, S. H. ; Lee, C. H. ; Shin, DongMin ; Lee, Y. R. ; Kim, M. S. / Glechoma hederacea suppresses RANKL-mediated osteoclastogenesis. In: Journal of Dental Research. 2014 ; Vol. 93, No. 7. pp. 685-690.
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abstract = "Glechoma hederacea (GH), commonly known as ground-ivy or gill-over-theground, has been extensively used in folk remedies for relieving symptoms of inflammatory disorders. However, the molecular mechanisms underlying the therapeutic action of GH are poorly understood. Here, we demonstrate that GH constituents inhibit osteoclastogenesis by abrogating receptor activator of nuclear κ-B ligand (RANKL)-induced free cytosolic Ca2+ ([Ca2+]i) oscillations. To evaluate the effect of GH on osteoclastogenesis, we assessed the formation of multi-nucleated cells (MNCs), enzymatic activity of tartrateresistant acidic phosphatase (TRAP), expression of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), and [Ca 2+]i alterations in response to treatment with GH ethanol extract (GHE) in primarily cultured bone marrow- derived macrophages (BMMs). Treatment of RANKL-stimulated or non-stimulated BMMs with GHE markedly suppressed MNC formation, TRAP activity, and NFATc1 expression in a dose-dependent manner. Additionally, GHE treatment induced a large transient elevation in [Ca 2+]i while suppressing RANKL-induced [Ca2+]i oscillations, which are essential for NFATc1 activation. GHE-evoked increase in [Ca 2+]i was dependent on extracellular Ca2+ and was inhibited by 1,4-dihydropyridine (DHP), inhibitor of voltage-gated Ca2+ channels (VGCCs), but was independent of storeoperated Ca2+ channels. Notably, after transient [Ca2+] elevation, treatment with GHE desensitized the VGCCs, resulting in an abrogation of RANKLinduced [Ca 2+]i oscillations and MNC formation. These findings demonstrate that treatment of BMMs with GHE suppresses RANKL-mediated osteoclastogenesis by activating and then desensitizing DHP-sensitive VGCCs, suggesting potential applications of GH in the treatment of bone disorders, such as periodontitis, osteoporosis, and rheumatoid arthritis.",
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Hwang, JK, Erkhembaatar, M, Gu, DR, Lee, SH, Lee, CH, Shin, D, Lee, YR & Kim, MS 2014, 'Glechoma hederacea suppresses RANKL-mediated osteoclastogenesis', Journal of Dental Research, vol. 93, no. 7, pp. 685-690. https://doi.org/10.1177/0022034514536579

Glechoma hederacea suppresses RANKL-mediated osteoclastogenesis. / Hwang, J. K.; Erkhembaatar, M.; Gu, D. R.; Lee, S. H.; Lee, C. H.; Shin, DongMin; Lee, Y. R.; Kim, M. S.

In: Journal of Dental Research, Vol. 93, No. 7, 01.01.2014, p. 685-690.

Research output: Contribution to journalArticle

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T1 - Glechoma hederacea suppresses RANKL-mediated osteoclastogenesis

AU - Hwang, J. K.

AU - Erkhembaatar, M.

AU - Gu, D. R.

AU - Lee, S. H.

AU - Lee, C. H.

AU - Shin, DongMin

AU - Lee, Y. R.

AU - Kim, M. S.

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N2 - Glechoma hederacea (GH), commonly known as ground-ivy or gill-over-theground, has been extensively used in folk remedies for relieving symptoms of inflammatory disorders. However, the molecular mechanisms underlying the therapeutic action of GH are poorly understood. Here, we demonstrate that GH constituents inhibit osteoclastogenesis by abrogating receptor activator of nuclear κ-B ligand (RANKL)-induced free cytosolic Ca2+ ([Ca2+]i) oscillations. To evaluate the effect of GH on osteoclastogenesis, we assessed the formation of multi-nucleated cells (MNCs), enzymatic activity of tartrateresistant acidic phosphatase (TRAP), expression of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), and [Ca 2+]i alterations in response to treatment with GH ethanol extract (GHE) in primarily cultured bone marrow- derived macrophages (BMMs). Treatment of RANKL-stimulated or non-stimulated BMMs with GHE markedly suppressed MNC formation, TRAP activity, and NFATc1 expression in a dose-dependent manner. Additionally, GHE treatment induced a large transient elevation in [Ca 2+]i while suppressing RANKL-induced [Ca2+]i oscillations, which are essential for NFATc1 activation. GHE-evoked increase in [Ca 2+]i was dependent on extracellular Ca2+ and was inhibited by 1,4-dihydropyridine (DHP), inhibitor of voltage-gated Ca2+ channels (VGCCs), but was independent of storeoperated Ca2+ channels. Notably, after transient [Ca2+] elevation, treatment with GHE desensitized the VGCCs, resulting in an abrogation of RANKLinduced [Ca 2+]i oscillations and MNC formation. These findings demonstrate that treatment of BMMs with GHE suppresses RANKL-mediated osteoclastogenesis by activating and then desensitizing DHP-sensitive VGCCs, suggesting potential applications of GH in the treatment of bone disorders, such as periodontitis, osteoporosis, and rheumatoid arthritis.

AB - Glechoma hederacea (GH), commonly known as ground-ivy or gill-over-theground, has been extensively used in folk remedies for relieving symptoms of inflammatory disorders. However, the molecular mechanisms underlying the therapeutic action of GH are poorly understood. Here, we demonstrate that GH constituents inhibit osteoclastogenesis by abrogating receptor activator of nuclear κ-B ligand (RANKL)-induced free cytosolic Ca2+ ([Ca2+]i) oscillations. To evaluate the effect of GH on osteoclastogenesis, we assessed the formation of multi-nucleated cells (MNCs), enzymatic activity of tartrateresistant acidic phosphatase (TRAP), expression of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), and [Ca 2+]i alterations in response to treatment with GH ethanol extract (GHE) in primarily cultured bone marrow- derived macrophages (BMMs). Treatment of RANKL-stimulated or non-stimulated BMMs with GHE markedly suppressed MNC formation, TRAP activity, and NFATc1 expression in a dose-dependent manner. Additionally, GHE treatment induced a large transient elevation in [Ca 2+]i while suppressing RANKL-induced [Ca2+]i oscillations, which are essential for NFATc1 activation. GHE-evoked increase in [Ca 2+]i was dependent on extracellular Ca2+ and was inhibited by 1,4-dihydropyridine (DHP), inhibitor of voltage-gated Ca2+ channels (VGCCs), but was independent of storeoperated Ca2+ channels. Notably, after transient [Ca2+] elevation, treatment with GHE desensitized the VGCCs, resulting in an abrogation of RANKLinduced [Ca 2+]i oscillations and MNC formation. These findings demonstrate that treatment of BMMs with GHE suppresses RANKL-mediated osteoclastogenesis by activating and then desensitizing DHP-sensitive VGCCs, suggesting potential applications of GH in the treatment of bone disorders, such as periodontitis, osteoporosis, and rheumatoid arthritis.

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