C Liu1,2, L Wang1,2, R Zhu1, H Liu1, R Ma1,3, B Chen1, L Li1, Y Guo1,4, Q Jia1, S Shi2, D Zhao1, F Mo1, B Zhao2, J Niu1, M Fu5, A N Orekhov6, D Brömme7, S Gao1, D Zhang8. 1. Diabetes Research Center, Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing, 100029, People's Republic of China. 2. Chinese Materia Medica School, Beijing University of Chinese Medicine, Beijing, 100029, China. 3. Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China. 4. The Third Affiliated Clinical Hospital, Beijing University of Chinese Medicine, Beijing, 100029, China. 5. The Research Institute of McGill University Health Center, Montreal, Quebec, H4A 3J1, Canada. 6. Laboratory of Angiopathology, Russian Academy of Medical Sciences, Institute of General Pathology and Pathophysiology, Moscow, 125315, Russia. 7. Department of Oral Biological & Medical Sciences, Faculty of Dentistry, The University of British Columbia, Vancouver, BC, V6T 1Z3, Canada. 8. Diabetes Research Center, Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing, 100029, People's Republic of China. dongwei1006@gmail.com.
Abstract
Rehmanniae Radix Preparata (RRP) improves bone quality in OVX rats through the regulation of bone homeostasis via increasing osteoblastogenesis and decreasing osteoclastogenesis, suggesting it has a potential for the development of new anti-osteoporotic drugs. INTRODUCTION: Determine the anti-osteoporotic effect of RRP in ovariectomized (OVX) rats and identify the signaling pathway involved in this process. METHODS: OVX rats were treated with RRP aqueous extract for 14 weeks. The serum levels of tartrate-resistant acid phosphatase (TRAP), receptor activator of nuclear factor kappa-Β ligand (RANKL), alkaline phosphatase (ALP), and osteoprotegerin (OPG) were determined by ELISA. Bone histopathological alterations were evaluated by H&E, Alizarin red S, and Safranin O staining. Bone mineral density (BMD) and bone microstructure in rat femurs and lumbar bones were determined by dual-energy X-ray absorptiometry and micro-computed tomography. Femoral bone strength was detected by a three-point bending assay. The expression of Phospho-glycogen synthase kinase 3 beta (p-GSK-3β), GSK-3β, Dickkopf-related protein 1 (DKK1), cathepsin K, OPG, RANKL, IGF-1, Runx2, β-catenin, and p-β-catenin was determined by western blot and/or immunohistochemical staining. RESULTS: Treatment of OVX rats with RRP aqueous extract rebuilt bone homeostasis demonstrated by increasing the levels of OPG as well as decreasing the levels of TRAP, RANKL, and ALP in serum. Furthermore, RRP treatment preserved BMD and mechanical strength by increasing cortical bone thickness and epiphyseal thickness as well as improving trabecular distribution in the femurs of OVX rats. In addition, RRP downregulated the expression of DKK1, sclerostin, RANKL, cathepsin K, and the ratio of p-β-catenin to β-catenin, along with upregulating the expression of IGF-1, β-catenin, and Runx2 and the ratio of p-GSK-3β to GSK-3β in the tibias and femurs of OVX rats. Echinacoside, jionoside A1/A2, acetoside, isoacetoside, jionoside B1, and jionoside B2 were identified in the RRP aqueous extract. CONCLUSION: RRP attenuates bone loss and improves bone quality in OVX rats partly through its regulation of the canonical Wnt/β-catenin signaling pathway, suggesting that RRP has the potential to provide a new source of anti-osteoporotic drugs.
Rehmanniae Radix Preparata (RRP) improves bone quality in OVX rats through the regulation of bone homeostasis via increasing osteoblastogenesis and decreasing osteoclastogenesis, suggesting it has a potential for the development of new anti-osteoporotic drugs. INTRODUCTION: Determine the anti-osteoporotic effect of RRP in ovariectomized (OVX) rats and identify the signaling pathway involved in this process. METHODS: OVX rats were treated with RRP aqueous extract for 14 weeks. The serum levels of tartrate-resistant acid phosphatase (TRAP), receptor activator of nuclear factor kappa-Β ligand (RANKL), alkaline phosphatase (ALP), and osteoprotegerin (OPG) were determined by ELISA. Bone histopathological alterations were evaluated by H&E, Alizarin red S, and Safranin O staining. Bone mineral density (BMD) and bone microstructure in rat femurs and lumbar bones were determined by dual-energy X-ray absorptiometry and micro-computed tomography. Femoral bone strength was detected by a three-point bending assay. The expression of Phospho-glycogen synthase kinase 3 beta (p-GSK-3β), GSK-3β, Dickkopf-related protein 1 (DKK1), cathepsin K, OPG, RANKL, IGF-1, Runx2, β-catenin, and p-β-catenin was determined by western blot and/or immunohistochemical staining. RESULTS: Treatment of OVX rats with RRP aqueous extract rebuilt bone homeostasis demonstrated by increasing the levels of OPG as well as decreasing the levels of TRAP, RANKL, and ALP in serum. Furthermore, RRP treatment preserved BMD and mechanical strength by increasing cortical bone thickness and epiphyseal thickness as well as improving trabecular distribution in the femurs of OVX rats. In addition, RRP downregulated the expression of DKK1, sclerostin, RANKL, cathepsin K, and the ratio of p-β-catenin to β-catenin, along with upregulating the expression of IGF-1, β-catenin, and Runx2 and the ratio of p-GSK-3β to GSK-3β in the tibias and femurs of OVX rats. Echinacoside, jionoside A1/A2, acetoside, isoacetoside, jionoside B1, and jionoside B2 were identified in the RRP aqueous extract. CONCLUSION: RRP attenuates bone loss and improves bone quality in OVX rats partly through its regulation of the canonical Wnt/β-catenin signaling pathway, suggesting that RRP has the potential to provide a new source of anti-osteoporotic drugs.
Authors: Ji Li; Ildiko Sarosi; Russell C Cattley; James Pretorius; Frank Asuncion; Mario Grisanti; Sean Morony; Stephen Adamu; Zhaopo Geng; Wanrong Qiu; Paul Kostenuik; David L Lacey; W Scott Simonet; Brad Bolon; Xueming Qian; Victoria Shalhoub; Michael S Ominsky; Hua Zhu Ke; Xiaodong Li; William G Richards Journal: Bone Date: 2006-05-26 Impact factor: 4.398