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Background: This study focused on the mechanisms where icariin inhibited chondrocyte apoptosis and angiogenesis by regulating the TDP-43 signaling pathway.

Methods: A rat osteoarthritis (OA) model was established by collagenase injection. Histological examination of the articular cartilage and synovial tissue was performed 6 weeks after operation. Cartilage cell line overexpressing TDP-43 and mesenchymal stem cell line (TDP43-MSCs) of the rat TDP43 gene were established.

Results: In OA rats transplanted with TDP43-mMSCs, TDP43 was highly expressed in chondrocytes (TDP43-HC), while TDP43 expression was low in HC and MSCs-HC (p < 0.05). After the intervention of MSCs-TDP43, high expression of TDP43 induced the apoptosis and death of chondrocytes. After the addition of icariin, late apoptosis and death of TDP43-HC were significantly attenuated. Apoptosis and death of HC, MSCs-HC, and TDP43-HC cells were effectively controlled with icariin, and no apparent cell death was found. ELISA showed that the VEGF and HIF-1 alpha were significantly higher in the rat OA model than the normal control rats.

Conclusion: TDP43-MSC transplantation interfered with the expression of TDP43 in the articular chondrocytes of OA rats, which may impact on inducing apoptosis of chondrocytes as well as inhibiting the proliferation of chondrocytes. Additionally, TDP43-MSCs appeared to promote the formation of neovascularization in the synovial tissue, which could be significantly attenuated by icariin.

Titel:	Icariin inhibits chondrocyte apoptosis and angiogenesis by regulating the TDP-43 signaling pathway.
Autor/in / Beteiligte Person:	Huang, H ; Zhang, ZF ; Qin, FW ; Tang, W ; Liu, DH ; Wu, PY ; Jiao, F
Link:	Zum Volltext
Zeitschrift:	Molecular genetics & genomic medicine, Jg. 7 (2019-04-01), Heft 4, S. e00586
Veröffentlichung:	[Hoboken, NJ] : John Wiley & Sons, [2013]-, 2019
Medientyp:	academicJournal
ISSN:	2324-9269 (electronic)
DOI:	10.1002/mgg3.586
Schlagwort:	Animals Cell Line Cells, Cultured Chondrocytes metabolism Male Mesenchymal Stem Cell Transplantation methods Mesenchymal Stem Cells metabolism Neovascularization, Physiologic Osteoarthritis therapy Rats Rats, Sprague-Dawley Signal Transduction Apoptosis Chondrocytes drug effects DNA-Binding Proteins metabolism Flavonoids pharmacology Osteoarthritis metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Mol Genet Genomic Med] 2019 Apr; Vol. 7 (4), pp. e00586. <i>Date of Electronic Publication: </i>2019 Feb 07. MeSH Terms: Apoptosis* ; Chondrocytes / drug effects ; DNA-Binding Proteins / metabolism ; Flavonoids / pharmacology ; Osteoarthritis / metabolism ; Animals ; Cell Line ; Cells, Cultured ; Chondrocytes / metabolism ; Male ; Mesenchymal Stem Cell Transplantation / methods ; Mesenchymal Stem Cells / metabolism ; Neovascularization, Physiologic ; Osteoarthritis / therapy ; Rats ; Rats, Sprague-Dawley ; Signal Transduction References: J Biol Chem. 2017 Mar 24;292(12):5089-5100. (PMID: 28167528) ; Int J Mol Med. 2015 Feb;35(2):325-32. (PMID: 25435376) ; Sports Health. 2015 Jan;7(1):38-44. (PMID: 25553211) ; Biomaterials. 2018 Apr;162:1-21. (PMID: 29428675) ; Osteoarthritis Cartilage. 2015 Nov;23(11):1989-98. (PMID: 26521745) ; Transplantation. 2015 Aug;99(8):1681-90. (PMID: 25822648) ; Exp Neurol. 2015 Nov;273:24-35. (PMID: 26222336) ; J Neurochem. 2013 Jul;126(2):288-300. (PMID: 23398327) ; J Chem Neuroanat. 2017 Apr;81:48-52. (PMID: 28163215) ; Arthritis Rheumatol. 2017 Jan;69(1):9-21. (PMID: 27564539) ; Biomed Pharmacother. 2017 Jan;85:362-371. (PMID: 27890430) ; Int J Mol Sci. 2015 Oct 30;16(11):26035-54. (PMID: 26528972) ; Cell Death Dis. 2015 Mar 26;6:e1702. (PMID: 25811799) ; Mol Genet Genomic Med. 2019 Apr;7(4):e00586. (PMID: 30734541) ; Apoptosis. 2015 Sep;20(9):1187-99. (PMID: 26184498) ; Nat Commun. 2016 Jan 07;7:10252. (PMID: 26738979) ; J Biomed Mater Res A. 2017 Aug;105(8):2343-2354. (PMID: 28387995) ; Stem Cells Dev. 2016 Nov 1;25(21):1659-1669. (PMID: 27554322) ; Front Immunol. 2016 Sep 27;7:392. (PMID: 27729913) Contributed Indexing: Keywords: TDP-43; VEGF; apoptosis; icariin; osteoarthritis Substance Nomenclature: 0 (DNA-Binding Proteins) ; 0 (Flavonoids) ; 0 (Tardbp protein, rat) ; VNM47R2QSQ (icariin) Entry Date(s): Date Created: 20190209 Date Completed: 20190521 Latest Revision: 20210109 Update Code: 20231215 PubMed Central ID: PMC6465670

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Icariin inhibits chondrocyte apoptosis and angiogenesis by regulating the TDP-43 signaling pathway.