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      The shared KEGG pathways between icariin-targeted genes and osteoporosis

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          Abstract

          Osteoporosis is a common metabolic bone disease that affects about 40% of postmenopausal women. Treatment options for osteoporosis are limited, however. Icariin is an herbal substance that has been shown to improve bone mass, but the mechanisms are largely unknown. Using bioinformatics analysis, we have identified the hub genes and KEGG pathways shared between icariin-targeted genes and osteoporosis. The top five shared KEGG pathways were the Toll-like receptor signaling pathway, adipocytokine pathway, neurotrophin signaling pathway, NOD-like receptor signaling, and B cell receptor signaling pathway; the hub genes were RELA, NFKBIA, and IKBKB, belonging to the NF-κB family. The identified icariin-targeted genes are involved in inflammation, insulin resistance, apoptosis, and immune responses, and regulate the PI3K-Akt, NF-κB, MAPK, and JNK signaling pathways. Our in vitro data show that icariin inhibits apoptosis in human mesenchymal stem cells by suppressing JNK/c-Jun signaling pathway. Together, these findings indicate that icariin exerts its anti-osteoporotic function by inhibiting JNK/c-Jun signaling pathway, and suggest that icariin may be a promising treatment option for osteoporosis.

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          JNK signaling in apoptosis.

          Jun N-terminal kinases or JNKs play a critical role in death receptor-initiated extrinsic as well as mitochondrial intrinsic apoptotic pathways. JNKs activate apoptotic signaling by the upregulation of pro-apoptotic genes through the transactivation of specific transcription factors or by directly modulating the activities of mitochondrial pro- and antiapoptotic proteins through distinct phosphorylation events. This review analyses our present understanding of the role of JNK in apoptotic signaling and the various mechanisms by which JNK promotes apoptosis.
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            The effect of icariin on bone metabolism and its potential clinical application.

            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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              Icariin induces osteogenic differentiation of bone mesenchymal stem cells in a MAPK-dependent manner.

              Icariin, a flavonoid isolated from Epimedium pubescens, has previously been identified to exert beneficial effects on preventing bone loss and promoting bone regeneration. However, molecular mechanisms for its anabolic action have, up to now, remained largely unknown.
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                Author and article information

                Journal
                Aging (Albany NY)
                Aging (Albany NY)
                Aging
                Aging (Albany NY)
                Impact Journals
                1945-4589
                15 May 2020
                07 May 2020
                : 12
                : 9
                : 8191-8201
                Affiliations
                [1 ]Department of Orthopedic Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
                [2 ]Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China
                [3 ]College of Dental Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA
                [4 ]Department of Orthopedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
                Author notes
                [*]

                Equal contribution

                Correspondence to: Yunfeng Yang; email: yangyunfeng1051@126.com
                Article
                103133 103133
                10.18632/aging.103133
                7244047
                32380477
                9b38378b-569f-4aaa-b3f4-aa3f9c103d31
                Copyright © 2020 Yu et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 30 December 2019
                : 30 March 2020
                Categories
                Research Paper

                Cell biology
                icariin,osteoporosis,bioinformatics,osteogenesis,jnk
                Cell biology
                icariin, osteoporosis, bioinformatics, osteogenesis, jnk

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