Inhibitory effect of Galgeun-tang on RANKL-induced osteoclast differentiation and bone loss in ovariectomized rats

In bone homeostasis, bone loss due to excessive osteoclasts and inflammation or osteolysis in the bone formation process cause bone diseases such as osteoporosis. Suppressing the accompanying oxidative stress such as ROS in this process is an important treatment strategy for bone disease. Therefore, in this study, the effect of (2R)-4-(4-hydroxyphenyl)-2-butanol 2-O-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside (BAG), an arylbutanoid glycoside isolated from Betula platyphylla var. japonica was investigated in RANKL-induced RAW264.7 cells and LPS-stimulated MC3E3-T1 cells. BAG inhibited the activity of TRAP, an important marker of osteoclast differentiation and F-actin ring formation, which has osteospecific structure. In addition, the protein and gene levels were suppressed of integrin β3 and CCL4, which play an important role in the osteoclast-induced bone resorption and migration of osteoclasts, and inhibited the production of ROS and restored the expression of antioxidant enzymes such as SOD and CAT lost by RANKL. The inhibitory effect of BAG on osteoclast differentiation and ROS production appears to be due to the inhibition of MAPKs phosphorylation and NF-κβ translocation, which play a major role in osteoclast differentiation. In addition, BAG inhibited ROS generated by LPS and effectively restores the mineralization of lost osteoblasts, thereby showing the effect of bone formation in the inflammatory situation accompanying bone loss by excessive osteoclasts, suggesting its potential as a new natural product-derived bone disease treatment.

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Potent inhibitory effect of Foeniculum vulgare Miller extract on osteoclast differentiation and ovariectomy-induced bone loss

International Journal of Molecular Medicine ◽

10.3892/ijmm.2012.950 ◽

2012 ◽

Cited By ~ 2

Author(s):

Sang-Han Lee

Keyword(s):

Bone Loss ◽

Osteoclast Differentiation ◽

Inhibitory Effect ◽

Foeniculum Vulgare ◽

Potent Inhibitory Effect ◽

Foeniculum Vulgare Miller

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Flemingia macrophyllaExtract Ameliorates Experimental Osteoporosis in Ovariectomized Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1093/ecam/nep179 ◽

2011 ◽

Vol 2011 ◽

pp. 1-9 ◽

Cited By ~ 7

Author(s):

Hui-Ya Ho ◽

Jin-Bin Wu ◽

Wen-Chuan Lin

Keyword(s):

Bone Resorption ◽

Bone Loss ◽

Bone Marrow Cells ◽

Serum Alkaline Phosphatase ◽

Osteoclast Differentiation ◽

Ethanolic Extract ◽

Ovariectomized Rats ◽

Native Plant ◽

Experimental Osteoporosis

Flemingia macrophylla(Leguminosae), a native plant of Taiwan, is used as folk medicine. Anin vitrostudy showed that a 75% ethanolic extract ofF. macrophylla(FME) inhibited osteoclast differentiation of cultured rat bone marrow cells, and the active component, lespedezaflavanone A (LDF-A), was isolated. It was found that oral administration of FME for 13 weeks suppressed bone loss in ovariectomized rats, an experimental model of osteoporosis. In addition, FME decreased urinary deoxypyridinoline concentrations but did not inhibit serum alkaline phosphatase activities, indicating that it ameliorated bone loss via inhibition of bone resorption. These results suggest that FME may represent a useful remedy for the treatment of bone resorption diseases, such as osteoporosis. In addition, LDF-A could be used as a marker compound to control the quality of FME.

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Clodronate has an inhibitory effect on bone loss in ovariectomized rats

Bone and Mineral ◽

10.1016/0169-6009(92)92037-q ◽

1992 ◽

Vol 17 ◽

pp. 174

Author(s):

R. Hannuniemi ◽

T. Virtamo

Keyword(s):

Bone Loss ◽

Inhibitory Effect ◽

Ovariectomized Rats

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Influence of vitamin D3 on inhibitory effect of vitamin K2 on bone loss in ovariectomized rats.

Folia Pharmacologica Japonica ◽

10.1254/fpj.104.101 ◽

1994 ◽

Vol 104 (2) ◽

pp. 101-109 ◽

Cited By ~ 15

Author(s):

Kuniko HARA ◽

Yasuhiro AKIYAMA ◽

Takashi TOMIUGA ◽

Masatoshi KOBAYASHI ◽

Tetsuya NAKAMURA ◽

...

Keyword(s):

Bone Loss ◽

Vitamin D3 ◽

Inhibitory Effect ◽

Vitamin K2 ◽

Ovariectomized Rats

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Water Extract ofDryopteris crassirhizomaAttenuates Bone Loss by Suppressing Osteoclast Differentiation and Function

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/852648 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 6

Author(s):

Hyunil Ha ◽

Ki-Shuk Shim ◽

Taesoo Kim ◽

Hyosun An ◽

Jin Yeul Ma

Keyword(s):

Bone Loss ◽

Protective Effect ◽

Osteoclast Differentiation ◽

Water Extract ◽

Inhibitory Effect ◽

Ring Structure ◽

Nuclear Factor ◽

Actin Ring ◽

Activated T Cells ◽

Osteoclast Precursors

The rhizome ofDryopteris crassirhizomahas been used as a traditional herbal medicine for treating various inflammatory and infectious diseases such as tapeworm infestation and mumps. In the present study, we investigated the bone protective effect of water extract of the rhizome ofDryopteris crassirhizoma(WEDC). We found that WEDC inhibits osteoclast differentiation via directly acting on osteoclast precursors. In osteoclast precursors, WEDC inhibited receptor activator of nuclear factor-κB ligand- (RANKL-) induced expression of c-Fos and nuclear factor of activated T cells cytoplasmic 1, a key downstream target of c-Fos during osteoclast differentiation. We found that WEDC inhibits RNAKL-induced activation of extracellular-regulated kinase and NF-κB that mediates c-Fos expression and osteoclast differentiation. In addition to the inhibitory effect of osteoclast differentiation, WEDC markedly suppressed bon-resorbing activity of mature osteoclasts, which was accompanied by disruption of actin ring structure. Furthermore, administration of WEDC suppressed RANKL-induced trabecular bone loss in mice. Collectively, our results demonstrate that WEDC inhibits not only osteoclast differentiation by inhibiting RANK signaling pathways in osteoclast precursors but also bone resorption by disrupting actin ring in mature osteoclasts, thereby contributing to its protective effect on bone loss.

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Ethanol Extracts of FreshDavallia formosana(WL1101) Inhibit Osteoclast Differentiation by Suppressing RANKL-Induced Nuclear Factor-κB Activation

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/647189 ◽

2013 ◽

Vol 2013 ◽

pp. 1-13 ◽

Cited By ~ 6

Author(s):

Tzu-Hung Lin ◽

Rong-Sen Yang ◽

Kuan-Chin Wang ◽

Dai-Hua Lu ◽

Houng-Chi Liou ◽

...

Keyword(s):

Bone Loss ◽

Nuclear Translocation ◽

Therapeutic Potential ◽

Osteoclast Differentiation ◽

Nuclear Factor Κb ◽

Ovariectomized Rats ◽

Nuclear Factor ◽

Receptor Activator ◽

Trabecular Bone Loss ◽

Ethanol Extracts

The rhizome ofDavallia formosanais commonly used to treat bone disease including bone fracture, arthritis, and osteoporosis in Chinese herbal medicine. Here, we report the effects of WL1101, the ethanol extracts of fresh rhizomes ofDavallia formosanaon ovariectomy-induced osteoporosis. In addition, excess activated bone-resorbing osteoclasts play crucial roles in inflammation-induced bone loss diseases, including rheumatoid arthritis and osteoporosis. In this study, we examined the effects of WL1101 on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis. Treatment with WL1101 significantly inhibited RANKL-stimulated osteoclastogenesis. Two isolated active compounds, ((−)-epicatechin) or WL14 (4-hydroxy-3-aminobenzoic acid) could also inhibit RANKL-induced osteoclastogenesis. WL1101 suppressed the RANKL-induced nuclear factor-κB (NF-κB) activation and nuclear translocation, which is the key process during osteoclastogenesis, by inhibiting the activation of IκB kinase (IKK) and IκBα. In animal model, oral administration of WL1101 (50 or 200 mg/kg/day) effectively decreased the excess bone resorption and significantly antagonized the trabecular bone loss in ovariectomized rats. Our results demonstrate that the ethanol extracts of fresh rhizomes ofDavallia formosanainhibit osteoclast differentiation via the inhibition of NF-κB activation and effectively ameliorate ovariectomy-induced osteoporosis. WL1101 may thus have therapeutic potential for the treatment of diseases associated with excessive osteoclastic activity.

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Differences in responses to X-ray exposure between osteoclast and osteoblast cells

Journal of Radiation Research ◽

10.1093/jrr/rrx026 ◽

2017 ◽

Vol 58 (6) ◽

pp. 791-802 ◽

Cited By ~ 16

Author(s):

Jian Zhang ◽

Ziyang Wang ◽

Anqing Wu ◽

Jing Nie ◽

Hailong Pei ◽

...

Keyword(s):

Bone Resorption ◽

Bone Loss ◽

Osteoclast Differentiation ◽

Inhibitory Effect ◽

Health Concern ◽

X Rays ◽

Potential Health ◽

X Ray ◽

Radiation Induced ◽

High Doses

Abstract Radiation-induced bone loss is a potential health concern for cancer patients undergoing radiotherapy. Enhanced bone resorption by osteoclasts and decreased bone formation by osteoblasts were thought to be the main reasons. In this study, we showed that both pre-differentiating and differentiating osteoclasts were relatively sensitive to X-rays compared with osteoblasts. X-rays decreased cell viability to a greater degree in RAW264.7 cells and in differentiating cells than than in osteoblastic MC3T3-E1 cells. X-rays at up to 8 Gy had little effects on osteoblast mineralization. In contrast, X-rays at 1 Gy induced enhanced osteoclastogenesis by enhanced cell fusion, but had no effects on bone resorption. A higher dose of X-rays at 8 Gy, however, had an inhibitory effect on bone resorption. In addition, actin ring formation was disrupted by 8 Gy of X-rays and reorganized into clusters. An increased activity of Caspase 3 was found after X-ray exposure. Actin disorganization and increased apoptosis may be the potential effects of X-rays at high doses, by inhibiting osteoclast differentiation. Taken together, our data indicate high radiosensitivity of osteoclasts. X-ray irradiation at relatively low doses can activate osteoclastogenesis, but not osteogenic differentiation. The radiosensitive osteoclasts are the potentially responsive cells for X-ray-induced bone loss.

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