Limits...
Inhibitory Effect of Chrysanthemum zawadskii Herbich var. latilobum Kitamura Extract on RANKL-Induced Osteoclast Differentiation.

Gu DR, Hwang JK, Erkhembaatar M, Kwon KB, Kim MS, Lee YR, Lee SH - Evid Based Complement Alternat Med (2013)

Bottom Line: However, these effects have not been tested on osteoclasts, the bone resorbing cells that regulate bone metabolism.CZE inhibited osteoclast differentiation and formation in a dose-dependent manner.These results indicate that CZE negatively regulates osteoclast differentiation and may be a therapeutic candidate for the treatment of various bone diseases, such as postmenopausal osteoporosis, rheumatoid arthritis, and periodontitis.

View Article: PubMed Central - PubMed

Affiliation: Center for Metabolic Function Regulation (CMFR), Wonkwang University School of Medicine, Iksan 570-749, Republic of Korea ; Department of Oral Microbiology and Immunology, College of Dentistry, Wonkwang University, Iksan 570-749, Republic of Korea.

ABSTRACT
Chrysanthemum zawadskii Herbich var. latilobum Kitamura, known as "Gujulcho" in Korea, has been used in traditional medicine to treat various inflammatory diseases, including rheumatoid arthritis. However, these effects have not been tested on osteoclasts, the bone resorbing cells that regulate bone metabolism. Here, we investigated the effects of C. zawadskii Herbich var. latilobum Kitamura ethanol extract (CZE) on osteoclast differentiation induced by treatment with the receptor activator of NF- κ B ligand (RANKL). CZE inhibited osteoclast differentiation and formation in a dose-dependent manner. The inhibitory effect of CZE on osteoclastogenesis was due to the suppression of ERK activation and the ablation of RANKL-stimulated Ca(2+)-oscillation via the inactivation of PLC γ 2, followed by the inhibition of CREB activation. These inhibitory effects of CZE resulted in a significant repression of c-Fos expression and a subsequent reduction of NFATc1, a key transcription factor for osteoclast differentiation, fusion, and activation in vitro and in vivo. These results indicate that CZE negatively regulates osteoclast differentiation and may be a therapeutic candidate for the treatment of various bone diseases, such as postmenopausal osteoporosis, rheumatoid arthritis, and periodontitis.

No MeSH data available.


Related in: MedlinePlus

Schematic diagram of the effect of CZE on RANKL-induced osteoclastogenesis. RANKL/RANK interaction may lead to the activation of MAPKs followed by c-Fos expression and alternatively activation of PLCγ2 inducing calcium signaling, which is critical for NFATc1 activation, followed by CREB activation and induction of c-Fos and NFATc1. CZE inhibited both RANKL-induced ERK and PLCγ activation signaling pathways.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3794617&req=5

fig6: Schematic diagram of the effect of CZE on RANKL-induced osteoclastogenesis. RANKL/RANK interaction may lead to the activation of MAPKs followed by c-Fos expression and alternatively activation of PLCγ2 inducing calcium signaling, which is critical for NFATc1 activation, followed by CREB activation and induction of c-Fos and NFATc1. CZE inhibited both RANKL-induced ERK and PLCγ activation signaling pathways.

Mentions: In addition to MAPK and NF-κB activation, RANKL/RANK signaling also activate phospholipase C gamma 2 (PLCγ2) and induces Ca2+-oscillation, followed by CREB activation [14, 25, 28]. CREB is critical for RANKL-stimulated NFATc1 and c-Fos induction in osteoclast precursors [14]. We first examined whether CZE affects the induction of Ca2+-oscillation by RANKL stimulation. BMMs were cultured with or without CZE under RANKL stimulation for 24 h. Intracellular Ca2+ concentration was measured as described previously. Control cells exhibited typical Ca2+-oscillation as shown in Figure 5(a). However, CZE-treated cells showed an irregular Ca2+-oscillation pattern with significantly increased intensity, but without increased frequency (Figure 5(b)). In addition, we acutely added CZE on control cells showing typical Ca2+-oscillation and then measured Ca2+ mobilization. As shown in Figure 5(c), Ca2+-oscillation was defective in these cells, with a large Ca2+ influx peak after CZE treatment. It seems that CZE may interact with some Ca2+ channels, which contributes to a substantial Ca2+ influx into the cells. We next examined whether RANKL-stimulated PLCγ2 activation is affected by CZE treatment. Phosphorylation of PLCγ2 in CZE-treated cells was significantly inhibited. In addition, the activation of CREB by RANKL was dramatically suppressed during osteoclast differentiation in CZE-treated cells. Collectively, these data demonstrate that CZE regulates not only MAPKs and NF-κB activation, but also PLCγ2 activation and RANKL-induced Ca2+-oscillation, which are important for CREB activation and c-Fos and NFATc1 induction in RANKL-stimulated osteoclast differentiation (Figure 6).


Inhibitory Effect of Chrysanthemum zawadskii Herbich var. latilobum Kitamura Extract on RANKL-Induced Osteoclast Differentiation.

Gu DR, Hwang JK, Erkhembaatar M, Kwon KB, Kim MS, Lee YR, Lee SH - Evid Based Complement Alternat Med (2013)

Schematic diagram of the effect of CZE on RANKL-induced osteoclastogenesis. RANKL/RANK interaction may lead to the activation of MAPKs followed by c-Fos expression and alternatively activation of PLCγ2 inducing calcium signaling, which is critical for NFATc1 activation, followed by CREB activation and induction of c-Fos and NFATc1. CZE inhibited both RANKL-induced ERK and PLCγ activation signaling pathways.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3794617&req=5

fig6: Schematic diagram of the effect of CZE on RANKL-induced osteoclastogenesis. RANKL/RANK interaction may lead to the activation of MAPKs followed by c-Fos expression and alternatively activation of PLCγ2 inducing calcium signaling, which is critical for NFATc1 activation, followed by CREB activation and induction of c-Fos and NFATc1. CZE inhibited both RANKL-induced ERK and PLCγ activation signaling pathways.
Mentions: In addition to MAPK and NF-κB activation, RANKL/RANK signaling also activate phospholipase C gamma 2 (PLCγ2) and induces Ca2+-oscillation, followed by CREB activation [14, 25, 28]. CREB is critical for RANKL-stimulated NFATc1 and c-Fos induction in osteoclast precursors [14]. We first examined whether CZE affects the induction of Ca2+-oscillation by RANKL stimulation. BMMs were cultured with or without CZE under RANKL stimulation for 24 h. Intracellular Ca2+ concentration was measured as described previously. Control cells exhibited typical Ca2+-oscillation as shown in Figure 5(a). However, CZE-treated cells showed an irregular Ca2+-oscillation pattern with significantly increased intensity, but without increased frequency (Figure 5(b)). In addition, we acutely added CZE on control cells showing typical Ca2+-oscillation and then measured Ca2+ mobilization. As shown in Figure 5(c), Ca2+-oscillation was defective in these cells, with a large Ca2+ influx peak after CZE treatment. It seems that CZE may interact with some Ca2+ channels, which contributes to a substantial Ca2+ influx into the cells. We next examined whether RANKL-stimulated PLCγ2 activation is affected by CZE treatment. Phosphorylation of PLCγ2 in CZE-treated cells was significantly inhibited. In addition, the activation of CREB by RANKL was dramatically suppressed during osteoclast differentiation in CZE-treated cells. Collectively, these data demonstrate that CZE regulates not only MAPKs and NF-κB activation, but also PLCγ2 activation and RANKL-induced Ca2+-oscillation, which are important for CREB activation and c-Fos and NFATc1 induction in RANKL-stimulated osteoclast differentiation (Figure 6).

Bottom Line: However, these effects have not been tested on osteoclasts, the bone resorbing cells that regulate bone metabolism.CZE inhibited osteoclast differentiation and formation in a dose-dependent manner.These results indicate that CZE negatively regulates osteoclast differentiation and may be a therapeutic candidate for the treatment of various bone diseases, such as postmenopausal osteoporosis, rheumatoid arthritis, and periodontitis.

View Article: PubMed Central - PubMed

Affiliation: Center for Metabolic Function Regulation (CMFR), Wonkwang University School of Medicine, Iksan 570-749, Republic of Korea ; Department of Oral Microbiology and Immunology, College of Dentistry, Wonkwang University, Iksan 570-749, Republic of Korea.

ABSTRACT
Chrysanthemum zawadskii Herbich var. latilobum Kitamura, known as "Gujulcho" in Korea, has been used in traditional medicine to treat various inflammatory diseases, including rheumatoid arthritis. However, these effects have not been tested on osteoclasts, the bone resorbing cells that regulate bone metabolism. Here, we investigated the effects of C. zawadskii Herbich var. latilobum Kitamura ethanol extract (CZE) on osteoclast differentiation induced by treatment with the receptor activator of NF- κ B ligand (RANKL). CZE inhibited osteoclast differentiation and formation in a dose-dependent manner. The inhibitory effect of CZE on osteoclastogenesis was due to the suppression of ERK activation and the ablation of RANKL-stimulated Ca(2+)-oscillation via the inactivation of PLC γ 2, followed by the inhibition of CREB activation. These inhibitory effects of CZE resulted in a significant repression of c-Fos expression and a subsequent reduction of NFATc1, a key transcription factor for osteoclast differentiation, fusion, and activation in vitro and in vivo. These results indicate that CZE negatively regulates osteoclast differentiation and may be a therapeutic candidate for the treatment of various bone diseases, such as postmenopausal osteoporosis, rheumatoid arthritis, and periodontitis.

No MeSH data available.


Related in: MedlinePlus