Positive Effects of Qing'e Pill(青娥丸)on Trabecular Microarchitecture and its Mechanical Properties in Osteopenic Ovariectomised Mice
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摘要
Objective: To investigate the impact of Qing'e Pill(青娥丸,QEP) on the cancellous bone microstructure and its effect on the level of β-catenin in a mouse model of postmenopausal osteoporosis.Methods: Ninety-six 8-week-old speci?c pathogen free C57 BL/6 mice were randomly divided into 4 groups(24/group): sham,ovariectomised osteoporosis model,oestradiol-treated,and QEP-treated groups.Three months after surgery,the third lumbar vertebra and left femur of the animals were dissected and scanned using micro-computed tomography(micro-CT) to acquire three-dimensional(3 D) parameters of their cancellous bone microstructure.The impact of ovariectomy,the effect of oestradiol and QEP intervention on cancellous bone microstructure,and the expression of β-catenin were evaluated.Results: The oestradioland the QEP-treated groups exhibited a signi?cant increase in the bone volume fraction,trabecular number,trabecular thickness,bone surface to bone volume ratio(BS/BV),and β-catenin expression compared with those of the model group(P<0.05).In contrast,the structure model index,trabecular separation,and BS/BV were signi?cantly decreased compared with those of the ovariectomised osteoporosis model group(P<0.05).No differences were observed in the above parameters between animals of the QEP-and oestradiol-treated groups.Conclusions: The increased β-catenin expression may be the mechanism underlying QEP's improvement of the cancellous bone microstructure in ovariectomised mice.Our ?ndings provide a scienti?c rationale for using QEP as a dietary supplement to prevent bone loss in postmenopausal women.
Objective: To investigate the impact of Qing'e Pill(青娥丸,QEP) on the cancellous bone microstructure and its effect on the level of β-catenin in a mouse model of postmenopausal osteoporosis.Methods: Ninety-six 8-week-old speci?c pathogen free C57 BL/6 mice were randomly divided into 4 groups(24/group): sham,ovariectomised osteoporosis model,oestradiol-treated,and QEP-treated groups.Three months after surgery,the third lumbar vertebra and left femur of the animals were dissected and scanned using micro-computed tomography(micro-CT) to acquire three-dimensional(3 D) parameters of their cancellous bone microstructure.The impact of ovariectomy,the effect of oestradiol and QEP intervention on cancellous bone microstructure,and the expression of β-catenin were evaluated.Results: The oestradioland the QEP-treated groups exhibited a signi?cant increase in the bone volume fraction,trabecular number,trabecular thickness,bone surface to bone volume ratio(BS/BV),and β-catenin expression compared with those of the model group(P<0.05).In contrast,the structure model index,trabecular separation,and BS/BV were signi?cantly decreased compared with those of the ovariectomised osteoporosis model group(P<0.05).No differences were observed in the above parameters between animals of the QEP-and oestradiol-treated groups.Conclusions: The increased β-catenin expression may be the mechanism underlying QEP's improvement of the cancellous bone microstructure in ovariectomised mice.Our ?ndings provide a scienti?c rationale for using QEP as a dietary supplement to prevent bone loss in postmenopausal women.
Objective: To investigate the impact of Qing'e Pill(青娥丸,QEP) on the cancellous bone microstructure and its effect on the level of β-catenin in a mouse model of postmenopausal osteoporosis.Methods: Ninety-six 8-week-old speci?c pathogen free C57 BL/6 mice were randomly divided into 4 groups(24/group): sham,ovariectomised osteoporosis model,oestradiol-treated,and QEP-treated groups.Three months after surgery,the third lumbar vertebra and left femur of the animals were dissected and scanned using micro-computed tomography(micro-CT) to acquire three-dimensional(3 D) parameters of their cancellous bone microstructure.The impact of ovariectomy,the effect of oestradiol and QEP intervention on cancellous bone microstructure,and the expression of β-catenin were evaluated.Results: The oestradioland the QEP-treated groups exhibited a signi?cant increase in the bone volume fraction,trabecular number,trabecular thickness,bone surface to bone volume ratio(BS/BV),and β-catenin expression compared with those of the model group(P<0.05).In contrast,the structure model index,trabecular separation,and BS/BV were signi?cantly decreased compared with those of the ovariectomised osteoporosis model group(P<0.05).No differences were observed in the above parameters between animals of the QEP-and oestradiol-treated groups.Conclusions: The increased β-catenin expression may be the mechanism underlying QEP's improvement of the cancellous bone microstructure in ovariectomised mice.Our ?ndings provide a scienti?c rationale for using QEP as a dietary supplement to prevent bone loss in postmenopausal women.
引文
1. Poole KE, Treece GM, Gee AH, Brown JP, McClung MR,Wang A, et al. Denosumab rapidly increases cortical bone in key locations of the femur:a 3D bone mapping study in women with osteoporosis. J Bone Miner Res 2015;30:46-54.
2. Klodowski K, Kaminski J, Nowicka K, Tarasiuk J, Wronski S, Swietek M, et al. Micro-imaging of implanted scaffolds using combined MRI and micro-CT. Comput Med Imag Graph 2014;38:458-468.
3. Knapp KM, Welsman JR, Hopkins SJ, Shallcross A,Fogelman I, Blake GM. Obesity increases precisionerrors in total body dual-energy X-ray absorptiometry measurements. J Clin Densitom 2015;18:209-216.
4. Ontario HQ. Utilization of DXA bone mineral densitometry in Ontario:an evidence-based analysis. Ont Health Technol Assess Ser 2006;6:1-180.
5. Wurnig MC, Calcagni M, Kenkel D, Vich M, Weiger M,Andreisek G, et al. Characterization of trabecular bone density with ultra-short echo-time MRI at 1.5, 3.0 and 7.0T comparison with micro-computed tomography. NMR Biomed 2014;27:1159-1166.
6. Effendy NM, Khamis MF, Soelaiman IN, Shuid AN. The effects of Labisia pumila on postmenopausal osteoporotic rat model:dose and time-dependent micro-CT analysis. J Xray Sci Technol 2014;22:503-518.
7. Ramli R, Khamis MF, Shuid AN. Bone micro-CT assessments in an orchidectomised rat model supplemented with Eurycoma longifolia. Evid Based Complement Alternat Med 2012:501858.
8. Holmen SL, Zylstra CR, Mukherjee A, Sigler RE, Faugere MC,Bouxsein ML, et al. Essential role of beta-catenin in postnatal bone acquisition. J Biol Chem 2005;280:21162-21168.
9. Chen Q, Zhuang Q, Mao W, Xu XM, Wang LH, Wang HB.Inhibitory effect of cryptotanshinone on angiogenesis and Wnt/β-catenin signaling pathway in human umbilical vein endothelial cells. Chin J Integr Med 2014;20(10):743-750
10. Xu YX, Wu CL, Wu Y, Tong PJ, Jin HT, Yu NZ, et al.Epimedium-derived flavonoids modulate the balance between osteogenic differentiation and adipogenic differentiation in bone marrow stromal cells of ovariectomized rats via Wnt/β-catenin signal pathway activation. Chin J Integr Med 2012;18:909-917.
11. Li FL, Deng H, Wang HW, Xu R, Chen J, Wang YF, et al. Effects of external application of Chinese medicine on diabetic ulcers and the expressions ofβ-catenin, c-myc and K6. Chin J Integr Med 2011;17:261-266.
12. Xu Y, Zhang ZJ, Geng F, Su SB, White KN, Bligh SW, et al. Treatment with Qing'e, a kidney-invigorating Chinese herbal formula, antagonizes the estrogen decline in ovariectomized mice. Rejuvenation Res 2010;13:479-488.
13. Contrera JF, Matthews EJ, Kruhlak NL, Benz RD.Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose. Regul Toxicol Pharmacol 2004;40:185-206.
14. Khajuria DK, Razdan R, Mahapatra DR. Zoledronic acid in combination with alfacalcidol has additive effects on trabecular microarchitecture and mechanical properties in osteopenic ovariectomized rats. J Orthop Sci 2014;19:646-656.
15. Jiang Y, Zhao J, Rosen C, Geusens P, Genant HK.Perspectives on bone mechanical properties and adaptiveresponse to mechanical challenge. J Clin Densitom1999;2:423-433.
16. Hahn M, Vogel M, Pompesius-Kempa M, Delling G.Trabecular bone pattern factor-a new parameter for simple quantification of bone microarchitecture. Bone1992;13:327-330.
17. Warden SJ, Hurst JA, Sanders MS, Turner CH, Burr DB,Li J. Bone adaptation to a mechanical loading program significantly increases skeletal fatigue resistance. J Bone Miner Res 2005;20:809-816.
18. Bolotin HH, Sievanen H. Inaccuracies inherent in dualenergy X-ray absorptiometry in vivo bone mineral density can seriously mislead diagnostic/prognostic interpretations of patient-specific bone fragility. J Bone Miner Res2001;16:799-805.
19. Legrand E, Chappard D, Pascaretti C, Duquenne M, Krebs S, Rohmer V, et al. Trabecular bone microarchitecture,bone mineral density, and vertebral fractures in male osteoporosis. J Bone Miner Res 2000;15:13-19.
20. Verborgt O, Gibson GJ, Schaffler MB. Loss of osteocyte integrity in association with microdamage and bone remodeling after fatigue in vivo. J Bone Miner Res 2000;15:60-67.
21. Park YS, Kim S, Oh SH, Park HJ, Lee S, Kim TI, et al.Comparison of alveolar ridge preservation methods using three-dimensional micro-computed tomographic analysis and two-dimensional histometric evaluation. Imaging Sci Dent 2014;44:143-148.
22. Neves AA, Jaecques S, Van Ende A, Cardoso MV,Coutinho E, Luhrs AK, et al. 3D-microleakage assessment of adhesive interfaces:exploratory findings by muCT. Dent Mater 2014;30:799-807.
23. Laib A, Barou O, Vico L, Lafage-Proust MH, Alexandre C, Rugsegger P. 3D micro-computed tomography of trabecular and cortical bone architecture with application to a rat model of immobilisation osteoporosis. Med Biol Eng Comput 2000;38:326-332.
24. Du LY, Umoh J, Nikolov HN, Pollmann SI, Lee TY,Holdsworth DW. A quality assurance phantom for the performance evaluation of volumetric micro-CT systems.Physics Med Biol 2007;52:7087-7108.
25. Kinney JH, Haupt DL, Balooch M, Ladd AJ, Ryaby JT,Lane NE. Three-dimensional morphometry of the L6vertebra in the ovariectomized rat model of osteoporosis:biomechanical implications. J Bone Miner Res2000;15:1981-1991.
26. Sirtori CR, Arnoldi A, Johnson SK. Phytoestrogens:end of a tale? Ann Med 2005;37:423-438.
27. Moon YJ, Wang X, Morris ME. Dietary flavonoids:effects on xenobiotic and carcinogen metabolism. Toxicol In Vitro2006;20:187-210.
28. Kouzmenko AP, Takeyama K, Ito S, Furutani T, Sawatsubashi S, Maki A, et al. Wnt/(3-catenin and estrogen signaling converge in vivo. J Biol Chem 2004;279:40255-40258.
29. Liedert A, Wagner L, Seefried L, Ebert R, Jakob F, Ignatius A. Estrogen receptor and Wnt signaling interact to regulate early gene expression in response to mechanical strain in osteoblastic cells. Biochem Biophys Res Commun2010;394:755-759.
30. Shuai B, Yang Y P, Shen L, Ke H. Effects of Qing'e Formula on the expression of bone metabolic markers and VDR mRNA in postmenopausal osteoporosis patients. Chin Med2014;5:145-152.
31. Xu XJ, Shen L, Yang YP, Zhu R, Shuai B, Li CG, et al.Serum beta-catenin Levels associated with the ratio of RANKL/OPG in patients with postmenopausal osteoporosis.Int J Endocrinol 2013;2013:534352.
32. Xu XJ, Shen L, Yang YP, Lu FR, Zhu R, Shuai B, et al.Serum sclerostin levels associated with lumbar spine bone mineral density and bone turnover markers in patients with postmenopausal osteoporosis. Chin Med J2013;126:2480-2484.
33. Shuai B, Shen L, Yang YP, Xie J, Shou ZX, Wei B. Low plasma adiponectin as a potential biomarker for osteonecrosis of the femoral head. J Rheumatol 2010;37:2151-2155.
34. Yang YP, Shuai B, Shen L, Xu XJ, Ma C, Lv L. Effect of Qing'e Formula on circulating sclerostin levels in patients with postmenopausal osteoporosis. J Huazhong Univ Sci Technol(Med Sci)2015;35:645-648.
2. Klodowski K, Kaminski J, Nowicka K, Tarasiuk J, Wronski S, Swietek M, et al. Micro-imaging of implanted scaffolds using combined MRI and micro-CT. Comput Med Imag Graph 2014;38:458-468.
3. Knapp KM, Welsman JR, Hopkins SJ, Shallcross A,Fogelman I, Blake GM. Obesity increases precisionerrors in total body dual-energy X-ray absorptiometry measurements. J Clin Densitom 2015;18:209-216.
4. Ontario HQ. Utilization of DXA bone mineral densitometry in Ontario:an evidence-based analysis. Ont Health Technol Assess Ser 2006;6:1-180.
5. Wurnig MC, Calcagni M, Kenkel D, Vich M, Weiger M,Andreisek G, et al. Characterization of trabecular bone density with ultra-short echo-time MRI at 1.5, 3.0 and 7.0T comparison with micro-computed tomography. NMR Biomed 2014;27:1159-1166.
6. Effendy NM, Khamis MF, Soelaiman IN, Shuid AN. The effects of Labisia pumila on postmenopausal osteoporotic rat model:dose and time-dependent micro-CT analysis. J Xray Sci Technol 2014;22:503-518.
7. Ramli R, Khamis MF, Shuid AN. Bone micro-CT assessments in an orchidectomised rat model supplemented with Eurycoma longifolia. Evid Based Complement Alternat Med 2012:501858.
8. Holmen SL, Zylstra CR, Mukherjee A, Sigler RE, Faugere MC,Bouxsein ML, et al. Essential role of beta-catenin in postnatal bone acquisition. J Biol Chem 2005;280:21162-21168.
9. Chen Q, Zhuang Q, Mao W, Xu XM, Wang LH, Wang HB.Inhibitory effect of cryptotanshinone on angiogenesis and Wnt/β-catenin signaling pathway in human umbilical vein endothelial cells. Chin J Integr Med 2014;20(10):743-750
10. Xu YX, Wu CL, Wu Y, Tong PJ, Jin HT, Yu NZ, et al.Epimedium-derived flavonoids modulate the balance between osteogenic differentiation and adipogenic differentiation in bone marrow stromal cells of ovariectomized rats via Wnt/β-catenin signal pathway activation. Chin J Integr Med 2012;18:909-917.
11. Li FL, Deng H, Wang HW, Xu R, Chen J, Wang YF, et al. Effects of external application of Chinese medicine on diabetic ulcers and the expressions ofβ-catenin, c-myc and K6. Chin J Integr Med 2011;17:261-266.
12. Xu Y, Zhang ZJ, Geng F, Su SB, White KN, Bligh SW, et al. Treatment with Qing'e, a kidney-invigorating Chinese herbal formula, antagonizes the estrogen decline in ovariectomized mice. Rejuvenation Res 2010;13:479-488.
13. Contrera JF, Matthews EJ, Kruhlak NL, Benz RD.Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose. Regul Toxicol Pharmacol 2004;40:185-206.
14. Khajuria DK, Razdan R, Mahapatra DR. Zoledronic acid in combination with alfacalcidol has additive effects on trabecular microarchitecture and mechanical properties in osteopenic ovariectomized rats. J Orthop Sci 2014;19:646-656.
15. Jiang Y, Zhao J, Rosen C, Geusens P, Genant HK.Perspectives on bone mechanical properties and adaptiveresponse to mechanical challenge. J Clin Densitom1999;2:423-433.
16. Hahn M, Vogel M, Pompesius-Kempa M, Delling G.Trabecular bone pattern factor-a new parameter for simple quantification of bone microarchitecture. Bone1992;13:327-330.
17. Warden SJ, Hurst JA, Sanders MS, Turner CH, Burr DB,Li J. Bone adaptation to a mechanical loading program significantly increases skeletal fatigue resistance. J Bone Miner Res 2005;20:809-816.
18. Bolotin HH, Sievanen H. Inaccuracies inherent in dualenergy X-ray absorptiometry in vivo bone mineral density can seriously mislead diagnostic/prognostic interpretations of patient-specific bone fragility. J Bone Miner Res2001;16:799-805.
19. Legrand E, Chappard D, Pascaretti C, Duquenne M, Krebs S, Rohmer V, et al. Trabecular bone microarchitecture,bone mineral density, and vertebral fractures in male osteoporosis. J Bone Miner Res 2000;15:13-19.
20. Verborgt O, Gibson GJ, Schaffler MB. Loss of osteocyte integrity in association with microdamage and bone remodeling after fatigue in vivo. J Bone Miner Res 2000;15:60-67.
21. Park YS, Kim S, Oh SH, Park HJ, Lee S, Kim TI, et al.Comparison of alveolar ridge preservation methods using three-dimensional micro-computed tomographic analysis and two-dimensional histometric evaluation. Imaging Sci Dent 2014;44:143-148.
22. Neves AA, Jaecques S, Van Ende A, Cardoso MV,Coutinho E, Luhrs AK, et al. 3D-microleakage assessment of adhesive interfaces:exploratory findings by muCT. Dent Mater 2014;30:799-807.
23. Laib A, Barou O, Vico L, Lafage-Proust MH, Alexandre C, Rugsegger P. 3D micro-computed tomography of trabecular and cortical bone architecture with application to a rat model of immobilisation osteoporosis. Med Biol Eng Comput 2000;38:326-332.
24. Du LY, Umoh J, Nikolov HN, Pollmann SI, Lee TY,Holdsworth DW. A quality assurance phantom for the performance evaluation of volumetric micro-CT systems.Physics Med Biol 2007;52:7087-7108.
25. Kinney JH, Haupt DL, Balooch M, Ladd AJ, Ryaby JT,Lane NE. Three-dimensional morphometry of the L6vertebra in the ovariectomized rat model of osteoporosis:biomechanical implications. J Bone Miner Res2000;15:1981-1991.
26. Sirtori CR, Arnoldi A, Johnson SK. Phytoestrogens:end of a tale? Ann Med 2005;37:423-438.
27. Moon YJ, Wang X, Morris ME. Dietary flavonoids:effects on xenobiotic and carcinogen metabolism. Toxicol In Vitro2006;20:187-210.
28. Kouzmenko AP, Takeyama K, Ito S, Furutani T, Sawatsubashi S, Maki A, et al. Wnt/(3-catenin and estrogen signaling converge in vivo. J Biol Chem 2004;279:40255-40258.
29. Liedert A, Wagner L, Seefried L, Ebert R, Jakob F, Ignatius A. Estrogen receptor and Wnt signaling interact to regulate early gene expression in response to mechanical strain in osteoblastic cells. Biochem Biophys Res Commun2010;394:755-759.
30. Shuai B, Yang Y P, Shen L, Ke H. Effects of Qing'e Formula on the expression of bone metabolic markers and VDR mRNA in postmenopausal osteoporosis patients. Chin Med2014;5:145-152.
31. Xu XJ, Shen L, Yang YP, Zhu R, Shuai B, Li CG, et al.Serum beta-catenin Levels associated with the ratio of RANKL/OPG in patients with postmenopausal osteoporosis.Int J Endocrinol 2013;2013:534352.
32. Xu XJ, Shen L, Yang YP, Lu FR, Zhu R, Shuai B, et al.Serum sclerostin levels associated with lumbar spine bone mineral density and bone turnover markers in patients with postmenopausal osteoporosis. Chin Med J2013;126:2480-2484.
33. Shuai B, Shen L, Yang YP, Xie J, Shou ZX, Wei B. Low plasma adiponectin as a potential biomarker for osteonecrosis of the femoral head. J Rheumatol 2010;37:2151-2155.
34. Yang YP, Shuai B, Shen L, Xu XJ, Ma C, Lv L. Effect of Qing'e Formula on circulating sclerostin levels in patients with postmenopausal osteoporosis. J Huazhong Univ Sci Technol(Med Sci)2015;35:645-648.
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