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The effect of icariin on bone metabolism and its potential clinical application

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Abstract

Osteoporosis is a bone disease characterized by reduced bone mass, which leads to increased risk of bone fractures, and poses a significant risk to public health, especially in the elderly population. The traditional Chinese medicinal herb Epimedii has been utilized for centuries to treat bone fracture and bone loss. Icariin is a prenylated flavonol glycoside isolated from Epimedium herb, and has been shown to be the main bioactive component. This review provides a comprehensive survey of previous studies on icariin, including its structure and function, effect on bone metabolism, and potential for clinical application. These studies show that icariin promotes bone formation by stimulating osteogenic differentiation of BMSCs (bone marrow-derived mesenchymal stem cells), while inhibiting osteoclastogenic differentiation and the bone resorption activity of osteoclasts. Furthermore, icariin has been shown to be more potent than other flavonoid compounds in promoting osteogenic differentiation and maturation of osteoblasts. A 24-month randomized double-blind placebo-controlled clinical trial reported that icariin was effective in preventing postmenopausal osteoporosis with relatively low side effects. In conclusion, icariin may represent a class of flavonoids with bone-promoting activity, which could be used as potential treatment of postmenopausal osteoporosis.

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Abbreviations

AAPH:

2,2′-azobis(2-amidinopropane) dihydrochloride

ALP:

alkaline phosphatase

ABCB1:

ATP-binding cassette subfamily B member 1

BMP:

bone morphogenetic protein

BMSC:

bone marrow-derived mesenchymal stem cells

Cebpb:

CCAAT/enhancer-binding protein β

CTX:

carboxy-terminal collagen cross-links

Col-1:

type I collagen

ERs:

estrogen receptors

ERK:

extracellular signal-regulated kinase

GSK-3β:

glycogen synthase kinase-3

Id-1:

inhibitor of DNA-binding 1

JNK:

c-Jun N terminal kinase

LPS:

lipopolysaccharide

MMP:

mitochondrial membrane potential

NO:

nitric oxide

OC:

osteocalcin

ONFH:

osteonecrosis of femoral head

OPG:

osteoprotegerin

·O2−:

superoxide anion

P-gp:

P-glycoprotein

ROS:

reactive oxygen species

Pparg:

peroxisome proliferator-activated receptor γ

Runx2:

runt-related transcription factor 2

RANKL:

receptor activator of nuclear factor kappa-B ligand

TRAP:

tartrate-resistant acid phosphatase

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Funding

This work was supported by the Natural Science Foundation of China (81371989), Guangdong Science and Technology Department Project (2015A030313776, 2016A050503008), and the Shenzhen Municipal Science and Technology Innovation Committee Project (JSGG20150331154931068, JCYJ20160301151248779, JCYJ20160229172757249, CXZZ20151015151249563, and CXZZ20150401152251209).

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  1. Z. Wang and D. Wang contributed equally to this work.

Authors and Affiliations

  1. Department of Spine Surgery and Institute of Orthopaedic Research, Shenzhen People’s Hospital, Jinan University School of Medicine, Shenzhen, 518020, China

    Z. Wang, D. Wang, D. Yang, W. Zhen & S. Peng

  2. Department of Outpatient Clinics, Shenzhen People’s Hospital, Jinan University School of Medicine, Shenzhen, 518020, China

    J. Zhang

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  1. Z. Wang
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Wang, Z., Wang, D., Yang, D. et al. The effect of icariin on bone metabolism and its potential clinical application. Osteoporos Int 29, 535–544 (2018). https://doi.org/10.1007/s00198-017-4255-1

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