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Achyranthes bidentata extract exerts osteoprotective effects on steroid-induced osteonecrosis of the femoral head in rats by regulating RANKL/RANK/OPG signaling.

Jiang Y, Zhang Y, Chen W, Liu C, Li X, Sun D, Liu Z, Xu Y, Mao X, Guo Q, Lin N - J Transl Med (2014)

Bottom Line: Then, the effects of ABE treatment on osteoclast differentiation and bone formation were also evaluated in vivo and in vitro.Interestingly, OPG downregulation, RANK and RANKL upregulation, and an increased ratio of RANKL to OPG in sera and necrotic femoral head could be reversed by ABE treatment, which also effectively inhibited RANKL-induced osteoclast differentiation and regulated RANKL and OPG expression of in vitro.ABE may prevent steroid-induced ONFH and alleviate steroid-induced bone deterioration by regulating the RANKL/RANK/OPG signaling pathway.

View Article: PubMed Central - PubMed

Affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No, 16, Nanxiaojie, Dongzhimennei, Beijing 100700, China. linna888@163.com.

ABSTRACT

Background: Steroid-induced osteonecrosis of the femoral head (steroid-induced ONFH) presents great challenges due to the various effects of steroids on multi-system pathways involved into osteoblast differentiation, osteoblast and osteoclast apoptosis, lipid metabolism, calcium metabolism and coagulation. As one of the most frequently used herbs in Traditional Chinese Medicine formulas that are prescribed for the regulation of bone and mineral metabolism, the therapeutic effects of Achyranthes bidentata on steroid-induced ONFH remain unclear. Thus, the aim of the current study was to verify whether Achyranthes bidentata extract (ABE) can be used to prevent steroid-induced ONFH and to investigate its underlying pharmacological mechanisms.

Methods: Steroid-induced ONFH rat models were established to evaluate the effects of ABE treatment on osteonecrotic changes and repair processes. Microfocal computed tomography (Micro-CT) was performed to assess the effects of ABE treatment on bone mass, microstructure, and vascularization. Then, the effects of ABE treatment on osteoclast differentiation and bone formation were also evaluated in vivo and in vitro. In addition, receptor activator of nuclear factor kappa B (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) expression in sera, femoral heads and bone marrow-derived mesenchymal stem cells (BMSCs) were detected at both protein and mRNA levels.

Results: The ratio of empty lacuna, adipose tissue area, and adipocyte perimeter in the bone marrow were markedly lower in the ABE treatment groups than in the model group. Micro-CT evaluation indicated that ABE treatment could improve the microstructure of the trabecular bone, increase bone mineral density and promote vascularization in steroid-induced ONFH rats. Moreover, ABE treatment inhibited osteoclast differentiation and activated bone formation markers. Interestingly, OPG downregulation, RANK and RANKL upregulation, and an increased ratio of RANKL to OPG in sera and necrotic femoral head could be reversed by ABE treatment, which also effectively inhibited RANKL-induced osteoclast differentiation and regulated RANKL and OPG expression of in vitro.

Conclusion: ABE may prevent steroid-induced ONFH and alleviate steroid-induced bone deterioration by regulating the RANKL/RANK/OPG signaling pathway.

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Related in: MedlinePlus

ABE regulates the expression of RANKL and OPG in bone marrow mesenchymal stem cells (BMSCs). BMSCs were cultured with or without different concentrations of ABE (0.16, 0.8, 4 μg/ml, respectively). Three days post-culture, supernatants were obtained to detectthe amounts of RANKL (A) and OPG (B) in the supernatants by ELISA. (C) refers to the ratio of RANKL/OPG in the supernatants. Data are represented as the mean ± SD of three independent experiments. *P < 0.05, **P < 0.01 and ***P < 0.001 significantly different from Model group.
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Fig9: ABE regulates the expression of RANKL and OPG in bone marrow mesenchymal stem cells (BMSCs). BMSCs were cultured with or without different concentrations of ABE (0.16, 0.8, 4 μg/ml, respectively). Three days post-culture, supernatants were obtained to detectthe amounts of RANKL (A) and OPG (B) in the supernatants by ELISA. (C) refers to the ratio of RANKL/OPG in the supernatants. Data are represented as the mean ± SD of three independent experiments. *P < 0.05, **P < 0.01 and ***P < 0.001 significantly different from Model group.

Mentions: Compared with model group, doses of 0.16 ~ 4 μg/ml ABE significantly reduced the expression of RANKL, and enhanced the expression of OPG in supernatant of BMSCs with a dose-related manner (Figure 9). More interestingly, ABE treatments markedly decreased the ratio of RANKL to OPG. MTT assay also showed that the anti-osteoclastogenic effect of ABE was not attributable to cellular toxicity (Figure 10).Figure 9


Achyranthes bidentata extract exerts osteoprotective effects on steroid-induced osteonecrosis of the femoral head in rats by regulating RANKL/RANK/OPG signaling.

Jiang Y, Zhang Y, Chen W, Liu C, Li X, Sun D, Liu Z, Xu Y, Mao X, Guo Q, Lin N - J Transl Med (2014)

ABE regulates the expression of RANKL and OPG in bone marrow mesenchymal stem cells (BMSCs). BMSCs were cultured with or without different concentrations of ABE (0.16, 0.8, 4 μg/ml, respectively). Three days post-culture, supernatants were obtained to detectthe amounts of RANKL (A) and OPG (B) in the supernatants by ELISA. (C) refers to the ratio of RANKL/OPG in the supernatants. Data are represented as the mean ± SD of three independent experiments. *P < 0.05, **P < 0.01 and ***P < 0.001 significantly different from Model group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4256888&req=5

Fig9: ABE regulates the expression of RANKL and OPG in bone marrow mesenchymal stem cells (BMSCs). BMSCs were cultured with or without different concentrations of ABE (0.16, 0.8, 4 μg/ml, respectively). Three days post-culture, supernatants were obtained to detectthe amounts of RANKL (A) and OPG (B) in the supernatants by ELISA. (C) refers to the ratio of RANKL/OPG in the supernatants. Data are represented as the mean ± SD of three independent experiments. *P < 0.05, **P < 0.01 and ***P < 0.001 significantly different from Model group.
Mentions: Compared with model group, doses of 0.16 ~ 4 μg/ml ABE significantly reduced the expression of RANKL, and enhanced the expression of OPG in supernatant of BMSCs with a dose-related manner (Figure 9). More interestingly, ABE treatments markedly decreased the ratio of RANKL to OPG. MTT assay also showed that the anti-osteoclastogenic effect of ABE was not attributable to cellular toxicity (Figure 10).Figure 9

Bottom Line: Then, the effects of ABE treatment on osteoclast differentiation and bone formation were also evaluated in vivo and in vitro.Interestingly, OPG downregulation, RANK and RANKL upregulation, and an increased ratio of RANKL to OPG in sera and necrotic femoral head could be reversed by ABE treatment, which also effectively inhibited RANKL-induced osteoclast differentiation and regulated RANKL and OPG expression of in vitro.ABE may prevent steroid-induced ONFH and alleviate steroid-induced bone deterioration by regulating the RANKL/RANK/OPG signaling pathway.

View Article: PubMed Central - PubMed

Affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No, 16, Nanxiaojie, Dongzhimennei, Beijing 100700, China. linna888@163.com.

ABSTRACT

Background: Steroid-induced osteonecrosis of the femoral head (steroid-induced ONFH) presents great challenges due to the various effects of steroids on multi-system pathways involved into osteoblast differentiation, osteoblast and osteoclast apoptosis, lipid metabolism, calcium metabolism and coagulation. As one of the most frequently used herbs in Traditional Chinese Medicine formulas that are prescribed for the regulation of bone and mineral metabolism, the therapeutic effects of Achyranthes bidentata on steroid-induced ONFH remain unclear. Thus, the aim of the current study was to verify whether Achyranthes bidentata extract (ABE) can be used to prevent steroid-induced ONFH and to investigate its underlying pharmacological mechanisms.

Methods: Steroid-induced ONFH rat models were established to evaluate the effects of ABE treatment on osteonecrotic changes and repair processes. Microfocal computed tomography (Micro-CT) was performed to assess the effects of ABE treatment on bone mass, microstructure, and vascularization. Then, the effects of ABE treatment on osteoclast differentiation and bone formation were also evaluated in vivo and in vitro. In addition, receptor activator of nuclear factor kappa B (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) expression in sera, femoral heads and bone marrow-derived mesenchymal stem cells (BMSCs) were detected at both protein and mRNA levels.

Results: The ratio of empty lacuna, adipose tissue area, and adipocyte perimeter in the bone marrow were markedly lower in the ABE treatment groups than in the model group. Micro-CT evaluation indicated that ABE treatment could improve the microstructure of the trabecular bone, increase bone mineral density and promote vascularization in steroid-induced ONFH rats. Moreover, ABE treatment inhibited osteoclast differentiation and activated bone formation markers. Interestingly, OPG downregulation, RANK and RANKL upregulation, and an increased ratio of RANKL to OPG in sera and necrotic femoral head could be reversed by ABE treatment, which also effectively inhibited RANKL-induced osteoclast differentiation and regulated RANKL and OPG expression of in vitro.

Conclusion: ABE may prevent steroid-induced ONFH and alleviate steroid-induced bone deterioration by regulating the RANKL/RANK/OPG signaling pathway.

Show MeSH
Related in: MedlinePlus