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      Icariin improves osteoporosis, inhibits the expression of PPARγ, C/EBPα, FABP4 mRNA, N1ICD and jagged1 proteins, and increases Notch2 mRNA in ovariectomized rats

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          Abstract

          Icariin (ICA) is a pharmacologically active flavonoid glycoside that shows promise in the treatment and prevention of osteoporosis (OP). However, the mechanisms underlying the anti-osteoporotic effects of ICA remain largely unclear. The present study used quantitative polymerase chain reaction, western blot and immunohistochemical analysis to examine the effects of ICA on several key targets in the Notch signaling pathway in bone tissue in ovariectomized rats. It was observed that ICA has a pronounced beneficial effect on OP rats and inhibits the expression of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding protein α (C/EBPα) and fatty acid-binding protein 4 (FABP4) mRNA. In addition, it was identified that ICA downregulates the expression of notch1 intracellular domain (N1ICD) and Jagged1 proteins in bone tissue, and suppresses the effect of N1ICD on Notch2 mRNA expression. It is proposed that ICA inhibits the differentiation of mesenchymal stem cells into adipocytes by inhibiting the expression of PPARγ, C/EBPα and FABP4 mRNA via the Notch signaling pathway. In addition, it is proposed that ICA inhibits the expression of Notch2 mRNA by suppressing the effect of N1ICD. In conclusion, the results provide further mechanistic evidence for the clinical efficacy of ICA in the treatment of OP.

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          Natural products for treatment of osteoporosis: The effects and mechanisms on promoting osteoblast-mediated bone formation.

          Jing An, Hao Yang, Qian Zhang … (2016)
          Osteoporosis is a systemic metabolic bone disease characterized by a reduction in bone mass, bone quality, and microarchitectural deterioration. An imbalance in bone remodeling that is caused by more osteoclast-mediated bone resorption than osteoblast-mediated bone formation results in such pathologic bone disorder. Traditional Chinese medicines (TCM) have long been used to prevent and treat osteoporosis and have received extensive attentions and researches at home and abroad, because they have fewer adverse reactions and are more suitable for long-term use compared with chemically synthesized medicines. Here, we put the emphasis on osteoblasts, summarized the detailed research progress on the active compounds derived from TCM with potential anti-osteoporosis effects and their molecular mechanisms on promoting osteoblast-mediated bone formation. It could be concluded that TCM with kidney-tonifying, spleen-tonifying, and stasis-removing effects all have the potential effects on treating osteoporosis. The active ingredients derived from TCM that possess effects on promoting osteoblasts proliferation and differentiation include flavonoids, glycosides, coumarins, terpenoids (sesquiterpenoids, monoterpenoids, diterpenoids), phenolic acids, phenols and others (tetrameric stilbene, anthraquinones, diarylheptanoids). And it was confirmed that the bone formation effect induced by the above natural products was regulated by the expressions of bone specific matrix proteins (ALP, BSP, OCN, OPN, COL I), transcription factor (Runx2, Cbfa1, Osx), signal pathways (MAPK, BMP), local factors (ROS, NO), OPG/RANKL system of osteoblasts and estrogen-like biological activities. All the studies provided theoretical basis for clinical application, as well as new drug research and development on treating osteoporosis.
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            Osteoclasts: what do they do and how do they do it?

            Steven Teitelbaum (2007)
            As Americans live longer, degenerative skeletal diseases, such as osteoporosis, become increasingly prevalent. Regardless of cause, osteoporosis reflects a relative enhancement of osteoclast activity. Thus, this unique bone resorptive cell is a prominent therapeutic target. A number of key observations provide insights into the mechanisms by which precursors commit to the osteoclast phenotype and how the mature cell degrades bone. The osteoclast is a member of the monocyte/macrophage family that differentiates under the aegis of two critical cytokines, namely RANK ligand and M-CSF. Tumor necrosis factor (TNF)-alpha also promotes osteoclastogenesis, particularly in states of inflammatory osteolysis such as that attending rheumatoid arthritis. Once differentiated, the osteoclast forms an intimate relationship with the bone surface via the alphavbeta3 integrin, which transmits matrix-derived, cytoskeleton-organizing, signals. These integrin-transmitted signals include activation of the associated proteins, c-src, syk, Vav3, and Rho GTPases. The organized cytoskeleton generates an isolated microenvironment between the cell's plasma membrane and the bone surface in which matrix mineral is mobilized by the acidic milieu and organic matrix is degraded by the lysosomal protease, cathepsin K. This review focuses on these and other molecules that mediate osteoclast differentiation or function and thus serve as candidate anti-osteoporosis therapeutic targets.
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              Cell and molecular biology of Notch.

              Ulla-Maj Fiuza, Alfonso Martinez Arias (2007)
              Notch signalling is a cell-cell communication process, which allows the establishment of patterns of gene expression and differentiation, regulates binary cell fate choice and the maintenance of stem cell populations. So far, the data published has elucidated the main players in the Notch signalling pathway. However, its regulatory mechanisms are exhibiting an increasing complexity which could account for the multitude of roles it has during development and in adult organisms. In this review, we will describe the multiple roles of Notch and how various factors can regulate Notch signalling.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Exp Ther Med
                Journal ID (iso-abbrev): Exp Ther Med
                Journal ID (publisher-id): ETM
                Title: Experimental and Therapeutic Medicine
                Publisher: D.A. Spandidos
                ISSN (Print): 1792-0981
                ISSN (Electronic): 1792-1015
                Publication date (Print): April 2017
                Publication date (Electronic): 15 February 2017
                Publication date PMC-release: 15 February 2017
                Volume: 13
                Issue: 4
                Pages: 1360-1368
                Affiliations
                [1 ]Department of Traditional Chinese Pharmacology, College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, P.R. China
                [2 ]Department of Traditional Chinese Medicine, First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510632, P.R. China
                Author notes
                Correspondence to: Professor Ronghua Zhang or Dr Li Yang, Department of Traditional Chinese Pharmacology, College of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou, Guangdong 510632, P.R. China, E-mail: tzrh@ 123456jnu.edu.cn , E-mail: doctormonkey@ 123456126.com
                [*]

                Contributed equally

                Article
                Publisher ID: ETM-0-0-4128
                DOI: 10.3892/etm.2017.4128
                PMC ID: 5377361
                PubMed ID: 28413478
                SO-VID: 3f1fecbf-68eb-40b8-9a8c-1676d3ea0bb9
                Copyright © Copyright: © Liu et al.
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                Date received : 09 July 2015
                Date accepted : 06 September 2016
                Categories
                Subject: Articles

                ScienceOpen disciplines: Medicine
                Keywords: icariin,osteoporosis,notch
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: icariin, osteoporosis, notch

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