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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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ABE treatment improves hyperlipidemia in rats with steroid-induced ONFH. Steroid hormone administration (the model group) induced marked hyperlipidemia, as indicated by significantly elevated TC (A), TG (B), LDL (C), ApoA1 (E), and ApoB (F) levels, but significantly decreased HDL levels (D). Doses of 10–22.5 g/kg ABE significantly reduced hyperlipidemia by decreasing TC (A), TG (B), LDL (C), ApoA1 (E), and ApoB (F) levels, and increasing HDL levels (D). Data are presented as the mean ± S.D. (n =20 for control, n =25 for model, n =20 for ABE 10 g/kg, ABE 15 g/kg, and 22.5 g/kg groups). # and ##: P <0.05 and P <0.01, respectively, in comparison with the control group. * and **: P <0.05 and P <0.01, respectively, in comparison with the model group.
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Fig5: ABE treatment improves hyperlipidemia in rats with steroid-induced ONFH. Steroid hormone administration (the model group) induced marked hyperlipidemia, as indicated by significantly elevated TC (A), TG (B), LDL (C), ApoA1 (E), and ApoB (F) levels, but significantly decreased HDL levels (D). Doses of 10–22.5 g/kg ABE significantly reduced hyperlipidemia by decreasing TC (A), TG (B), LDL (C), ApoA1 (E), and ApoB (F) levels, and increasing HDL levels (D). Data are presented as the mean ± S.D. (n =20 for control, n =25 for model, n =20 for ABE 10 g/kg, ABE 15 g/kg, and 22.5 g/kg groups). # and ##: P <0.05 and P <0.01, respectively, in comparison with the control group. * and **: P <0.05 and P <0.01, respectively, in comparison with the model group.

Mentions: Blood chemistry data showed that steroid hormone administration (model group) induced marked hyperlipidemia. Steroid administration significantly elevated TG (Figure 5B), TC (Figure 5A), LDL (Figure 5C), ApoA1 (Figure 5E) and ApoB (Figure 5F) levels, but significantly decreased HDL levels (Figure 5D). Administration of 10–22.5 g/kg ABE dose-dependently improved hyperlipidemia by decreasing TG (P <0.01, Figure 5B), TC (P <0.01, Figure 5A), LDL (P <0.05, Figure 5C), ApoA1 (P <0.05, Figure 5E), and ApoB (P <0.05, Figure 5F) levels, and increasing HDL levels (P <0.05, Figure 5D).Figure 5


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 treatment improves hyperlipidemia in rats with steroid-induced ONFH. Steroid hormone administration (the model group) induced marked hyperlipidemia, as indicated by significantly elevated TC (A), TG (B), LDL (C), ApoA1 (E), and ApoB (F) levels, but significantly decreased HDL levels (D). Doses of 10–22.5 g/kg ABE significantly reduced hyperlipidemia by decreasing TC (A), TG (B), LDL (C), ApoA1 (E), and ApoB (F) levels, and increasing HDL levels (D). Data are presented as the mean ± S.D. (n =20 for control, n =25 for model, n =20 for ABE 10 g/kg, ABE 15 g/kg, and 22.5 g/kg groups). # and ##: P <0.05 and P <0.01, respectively, in comparison with the control group. * and **: P <0.05 and P <0.01, respectively, in comparison with the model group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig5: ABE treatment improves hyperlipidemia in rats with steroid-induced ONFH. Steroid hormone administration (the model group) induced marked hyperlipidemia, as indicated by significantly elevated TC (A), TG (B), LDL (C), ApoA1 (E), and ApoB (F) levels, but significantly decreased HDL levels (D). Doses of 10–22.5 g/kg ABE significantly reduced hyperlipidemia by decreasing TC (A), TG (B), LDL (C), ApoA1 (E), and ApoB (F) levels, and increasing HDL levels (D). Data are presented as the mean ± S.D. (n =20 for control, n =25 for model, n =20 for ABE 10 g/kg, ABE 15 g/kg, and 22.5 g/kg groups). # and ##: P <0.05 and P <0.01, respectively, in comparison with the control group. * and **: P <0.05 and P <0.01, respectively, in comparison with the model group.
Mentions: Blood chemistry data showed that steroid hormone administration (model group) induced marked hyperlipidemia. Steroid administration significantly elevated TG (Figure 5B), TC (Figure 5A), LDL (Figure 5C), ApoA1 (Figure 5E) and ApoB (Figure 5F) levels, but significantly decreased HDL levels (Figure 5D). Administration of 10–22.5 g/kg ABE dose-dependently improved hyperlipidemia by decreasing TG (P <0.01, Figure 5B), TC (P <0.01, Figure 5A), LDL (P <0.05, Figure 5C), ApoA1 (P <0.05, Figure 5E), and ApoB (P <0.05, Figure 5F) levels, and increasing HDL levels (P <0.05, Figure 5D).Figure 5

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