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

Ying-xing Xu; Cheng-liang Wu; Yan Wu; Pei-jian Tong; Hong-ting Jin; Nan-ze Yu; Lu-wei Xiao

doi:10.1007/s11655-012-1294-2

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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

Updated：2021-08-27

- 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
- Chinese Journal of Integrative Medicine Vol. 18, Issue 12, Pages: 909-917(2012)
- Affiliations：
  
  1. Research Institution of Orthopaedics and Traumatology, Zhejiang Traditional Chinese Medical University,Hangzhou,China
  2. Department of Orthopaedics and Traumatology, Chinese Medicine Hospital,Yunnan Province,Yuxi,China
  3. The First Clinical Medical College, Zhejiang University of Traditional Chinese Medicine,Hangzhou,China
- Author bio：
- Funds：
- DOI：10.1007/s11655-012-1294-2
  CLC：
- Published：2012，
  
  Published Online：13 December 2012，
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Xu, Yx., Wu, Cl., Wu, Y. 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. 18, 909–917 (2012). https://doi.org/10.1007/s11655-012-1294-2

Ying-xing Xu, Cheng-liang Wu, Yan Wu, 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. [J]. Chinese Journal of Integrative Medicine 18(12):909-917(2012)
Xu, Yx., Wu, Cl., Wu, Y. 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. 18, 909–917 (2012). https://doi.org/10.1007/s11655-012-1294-2 DOI：

Ying-xing Xu, Cheng-liang Wu, Yan Wu, 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. [J]. Chinese Journal of Integrative Medicine 18(12):909-917(2012) DOI： 10.1007/s11655-012-1294-2.

摘要

To observe the function of wnt/β-catenin signal pathway on the process that epimedium-derived flavonoids (EFs) regulate the balance between osteogenic differentiation and adipogenic differentiation in bone marrow stromal cells of ovariectomized rats

and to provide an experimental evidence for the mechanism of EFs on treating postmenopausal osteoporosis. Bone marrow stromal cells from ovariectomized rats were separated and cultivated in the condition of osteoinductive medium or liquid medium for 15 days. Low- (1 μg/mL)

medium- (10 μg/mL) and high- (100 μg/mL) dose EFs were administrated correspondingly. Alkaline phosphatase (ALP) staining

ALP activity determination

oil red O staining and realtime polymerese chain reaction (RT-PCR) were used to determine the effect of EFs on osteogenic differentiation and adipogenic differentiation in bone marrow stromal cells of ovariectomized rats. Moreover

in order to explore the mechanism of EFs on osteogenic differentiation and adipogenic differentiation in bone marrow stromal cells of ovariectomized rats

Dickkopf-related protein 1 (DKK1) was used in the medium group. Enzymelinked immunosorbent assay (ELISA) and RT-PCR were used to determine mRNA levels of β-catenin

low density lipoprotein receptor-related protein 5 (LRP5) and T cell factor (TCF) protein

known as wnt/β-catenin signal pathway related factors. EFs increased mRNA expression levels of ALP and early osteoblast differentiation factors

such as runt-related transcription factor 2 (Runx2)

osteocalcin and collagen I

and decreased mRNA expression levels of fat generation factors

such as peroxisome proliferator activated receptor gamma 2 (PPARγ-2) and CCAAT enhancer-binding protein-α (C/EBPα) in a dose-dependent manner. While osteoblast differentiation factors were down-regulated

fat generation factors were up-regulated when DKK1 was applied. Also EFs up-regulated mRNA expression levels of β-catenin

LRP5 and TCF protein which could be blocked by DKK1. EFs regulate the balance between osteogenic differentiation and adipogenic differentiation in bone marrow stromal cells of ovariectomized rats by activating wnt/β-catenin signal pathway

which may be an important molecular mechanism of EFs on treating postmenopausal osteoporosis.

Abstract

medium- (10 μg/mL) and high- (100 μg/mL) dose EFs were administrated correspondingly. Alkaline phosphatase (ALP) staining

ALP activity determination

in order to explore the mechanism of EFs on osteogenic differentiation and adipogenic differentiation in bone marrow stromal cells of ovariectomized rats

Dickkopf-related protein 1 (DKK1) was used in the medium group. Enzymelinked immunosorbent assay (ELISA) and RT-PCR were used to determine mRNA levels of β-catenin

low density lipoprotein receptor-related protein 5 (LRP5) and T cell factor (TCF) protein

known as wnt/β-catenin signal pathway related factors. EFs increased mRNA expression levels of ALP and early osteoblast differentiation factors

such as runt-related transcription factor 2 (Runx2)

osteocalcin and collagen I

and decreased mRNA expression levels of fat generation factors

fat generation factors were up-regulated when DKK1 was applied. Also EFs up-regulated mRNA expression levels of β-catenin

which may be an important molecular mechanism of EFs on treating postmenopausal osteoporosis.

关键词

wnt/β-catenin signal pathwayepimedium-derived flavonoidsbone marrow stromal cellsOsteoporosisosteogenesisadipogenesiscell differentiation

Keywords

wnt/β-catenin signal pathwayepimedium-derived flavonoidsbone marrow stromal cellsOsteoporosisosteogenesisadipogenesiscell differentiation

references

Meuniher P, Aaron J, Edouard C, Vignon G. Osteoporosis and the replacement of cell populations of the marrow by adipose tissue. A quantitative study of 84 iliac bone biopsies. Clin Orthop Relat Res 1971;80:147–154.

Rodriguez JP, Garat S, Gajardo H, Pino AM, Seitz G. Abnormal osteogenesis in osteoporotic patients is reflected by altered mesenchymal stem cells dynamics. J Cell Biochem 1999;75:414–423.

Rodriguez JP, Montecinos L, Rios S, Reyes P, Martinez J. Mesenchymal stem cells from osteoporotic patients produce a type I collagen-deficient extracellular matrix favoring adipogenic differentiation. J Cell Biochem 2000;79:557–565.

Qiu W, Andersen TE, Bollerslev J, Mandrup S, Abdallah BM, Kassem M. Patients with high bone mass phenotype exhibit enhanced osteoblast differentiation and inhibition of adipogenesis of human mesenchymal stem cells. J Bone Miner Res 2007;22:1720–1731.

Bennett CN, Longo KA, Wright WS, Suva LJ, Lane TF, Hankenson KD, et al. Regulation of osteoblastogenesis and bone mass by Wnt10b. Proc Natl Acad Sci U S A 2005;102:3324–3329.

Zhang G, Qin L, Shi Y. Epimedium-derived phytoestrogen flavonoids exert beneficial effect on preventing bone loss in late postmenopausal women: a 24-month randomized, double-blind and placebo-controlled trial. J Bone Miner Res 2007;22:1072–1079.

Peng S, Zhang G, He Y, Wang X, Leung P, Leung K, et al. Epimedium-derived flavonoids promote osteoblastogenesis and suppress adipogenesis in bone marrow stromal cells while exerting an anabolic effect on osteoporotic bone. Bone 2009;45:534–544.

Li D, Li L, Wu J. Adipogenic potential of bone marrow mesenchymal stem cells derived from ovariectomized rats. J Biomed Eng (Chin) 2007;24:641–645.

Li DJ, Ge DX, Wu WC, Wu J, Li L. Osteogenic potential of bone marrow mesenchymal stem cells from ovariectomied osteoporotic rat. J Sichuan Univ (Med Sci, Chin) 2005;36:318–321.

Gaur T, Lengner CJ, Hovhannisyan H, Bhat RA, Bodine PVN, Komm BS, et al. Canonical WNT signaling promotes osteogenesis by directly stimulating runx2 gene expression. J Biol Chem 2005;280:33132–33140.

Zhang Y, Deng X, Scheller EL, Kwon TG, Lahann J, Franceschi RT, et al. The effects of Runx 2 immobilization on poly (epsilon-caprolactone) on osteoblast differentiation of bone marrow stromal cells in vitro. Biomaterials 2010;31:3231–3236.

Wang FS, Ko JY, Yeh DW, Ke HC, Wu HL. Modulation of Dickkopf-1 attenuates glucocorticoid induction of osteoblast apoptosis, adipocytic differentiation, and bone mass loss. Endocrinology 2008;149:1793–1801.

Gustafson B, Smith U. Cytokines promote Wnt signaling and inflammation and impair the normal differentiation and lipid accumulation in 3T3-L1 preadipocytes. J Biol Chem 2006;281:9507–9516.

Franceschi RT, Xiao G. Regulation of the osteoblast-specific transcription factor, Runx2: responsiveness to multiple signal transduction pathways. J Cell Biochem 2003;88:446–454.

Karsenty G, Ducy P, Starbuck M, Priemel M, Shen J, Geoffroy V, et al. Cbfa1 as a regulator of osteoblast differentiation and function. Bone 1999;25:107–108.

Lin TH, Yang RS, Tang CH, Lin CP, Fu WM. PPAR gamma inhibits osteogenesis via the down-regulation of the expression of COX-2 and iNOS in rats. Bone 2007;41:562–574.

Schadinger SE, Bucher NL, Schreiber BM, Farmer SR. PPAR gamma 2 regulates lipogenesis and lipid accumulation in steatotic hepatocytes. Am J Physiol Endocrinol Metab 2005;288:E1195–E1205.

Jiang MS, Lane MD. Sequential repression and activation of the CCAAT enhancer-binding protein-α (C/EBPα) gene during adipogenesis. Proc Natl Acad Sci U S A 2000;7:12519–12523.

Valeria P. The Role of C/EBP isoforms in the control of inflammatory and native immunity functions. J Biol Chem 1998;273:29279–29282.

Darlington GJ, Ross SE, MacDougald OA. The role of C/EBP genes in adipocyte differentiation. J Biol Chem 1998;273:30057–30060.

Ai M, Holmen SL, Van HW, Williams BO, Warman ML. Reduced affinity to and inhibition by DKK1 form a common mechanism by which high bone mass-associated missense mutations in LRP5 affect canonical Wnt signaling. Mol Cell Biol 2005;25:4946–4955.

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