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Context: Icariin has attracted increasing attention because of its wide variety of pharmacological effects.

Objective: This study investigates whether icariin could promote fracture healing in young and old rats and its mechanisms.

Materials and Methods: A Wistar rat model for the tibia fracture in relatively young and old rats, respectively, was established. The rats were divided into four groups: model group, L-icariin (50 mg/kg icariin), M-icariin (100 mg/kg icariin) and H-icariin (200 mg/kg icariin), and intragastric administration of icariin was performed for 10 days or 20 days. In addition, isolated and cultured rat bone mesenchymal stem cells (rBMSCs) from young and old rats were cultured with 5% and 20% of icariin-containing serum, respectively, then cell viability and alkaline phosphatase (ALP) activity were measured.

Results: Icariin administration induced the expression of Runx2, Osterix, BMP-2, p-Smad5 and osteocalcin secretion (young rats: model: 2.50 ± 0.71; L-icariin: 10.10 ± 1.55; M-icariin: 24.95 ± 2.19; H-icariin: 36.80 ± 2.26; old rats: model: 1.55 ± 0.49; L-icariin:6.55 ± 0.50; M-icariin: 15.00 ± 0.85; H-icariin:20.50 ± 2.27) at the fracture site, and increased the levels of bone formation markers (OC, BAP, NTX-1 and CTX-1) in a dose-dependent manner. In vitro , icariin treatment promoted rBMSC viability, increased ALP activity and the expression of BMP-2/Smad5/Runx2 pathway proteins.

Discussion and Conclusions: Icariin may accelerate fracture healing by activating the BMP-2/Smad5/Runx2 pathway in relatively young and old rats. The research on the mechanism of icariin to promote fracture healing can provide a theoretical basis for the clinical application and promotion of icariin.

Titel:	Effects of icariin on the fracture healing in young and old rats and its mechanism.
Autor/in / Beteiligte Person:	Zhang, X ; Chen, Y ; Zhang, C ; Xia, T ; Han, J ; Song, S ; Xu, C ; Chen, F
Link:	Zum Volltext
Zeitschrift:	Pharmaceutical biology, Jg. 59 (2021-12-01), Heft 1, S. 1245
Veröffentlichung:	[London] : Taylor & Francis ; <i>Original Publication</i>: Lisse, the Netherlands : Swets & Zeitlinger, c1998-, 2021
Medientyp:	academicJournal
ISSN:	1744-5116 (electronic)
DOI:	10.1080/13880209.2021.1972121
Schlagwort:	Age Factors Alkaline Phosphatase metabolism Animals Cell Survival drug effects Cells, Cultured Dose-Response Relationship, Drug Female Flavonoids administration & dosage Male Mesenchymal Stem Cells cytology Osteocalcin metabolism Rats Rats, Wistar Tibial Fractures metabolism Flavonoids pharmacology Fracture Healing drug effects Mesenchymal Stem Cells drug effects Tibial Fractures drug therapy
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Pharm Biol] 2021 Dec; Vol. 59 (1), pp. 1245-1255. MeSH Terms: Flavonoids / pharmacology ; Fracture Healing / drug effects ; Mesenchymal Stem Cells / drug effects ; Tibial Fractures / drug therapy ; Age Factors ; Alkaline Phosphatase / metabolism ; Animals ; Cell Survival / drug effects ; Cells, Cultured ; Dose-Response Relationship, Drug ; Female ; Flavonoids / administration & dosage ; Male ; Mesenchymal Stem Cells / cytology ; Osteocalcin / metabolism ; Rats ; Rats, Wistar ; Tibial Fractures / metabolism References: BMC Med. 2011 May 31;9:66. (PMID: 21627784) ; Zhongguo Gu Shang. 2017 Aug 25;30(8):743-750. (PMID: 29455507) ; Zhongguo Gu Shang. 2017 Aug 25;30(8):777-782. (PMID: 29455515) ; Nat Prod Res. 2017 Nov;31(22):2621-2628. (PMID: 28278623) ; Nephrol Dial Transplant. 2014 Aug;29(8):1532-8. (PMID: 24642419) ; Biol Proced Online. 2018 Jul 1;20:15. (PMID: 29988477) ; Injury. 2003 Jul;34(7):477-9. (PMID: 12832170) ; Int J Biol Sci. 2013 Nov 21;9(10):1089-98. (PMID: 24339730) ; Biochim Biophys Acta Gen Subj. 2018 Jul;1862(7):1680-1692. (PMID: 29679717) ; Ann N Y Acad Sci. 2017 Dec;1409(1):79-84. (PMID: 29044594) ; Osteoporos Int. 2018 Mar;29(3):535-544. (PMID: 29110063) ; Transfusion. 1999 Apr;39(4):410-4. (PMID: 10220269) ; Int J Clin Exp Med. 2015 May 15;8(5):7125-33. (PMID: 26221250) ; Curr Pharm Biotechnol. 2020;21(15):1645-1653. (PMID: 32525771) ; Injury. 2007 Mar;38 Suppl 1:S81-9. (PMID: 17383489) ; Curr Opin Genet Dev. 2003 Feb;13(1):43-7. (PMID: 12573434) ; J Bone Joint Surg Am. 2001;83-A Suppl 1(Pt 1):S15-22. (PMID: 11263661) ; FASEB J. 2015 Apr;29(4):1143-52. (PMID: 25466891) ; Di Yi Jun Yi Da Xue Xue Bao. 2004 Jun;24(6):708-10. (PMID: 15201098) ; Bull Exp Biol Med. 2002 Feb;133(2):103-9. (PMID: 12428273) ; Cell Transplant. 2015;24(12):2643-55. (PMID: 25647659) ; Cell Physiol Biochem. 2018;46(4):1727-1736. (PMID: 29698972) ; Injury. 2007 Mar;38 Suppl 1:S90-9. (PMID: 17383490) ; Int J Mol Med. 2016 Apr;37(4):901-10. (PMID: 26935542) ; Front Pharmacol. 2017 Oct 31;8:784. (PMID: 29163169) ; Am J Chin Med. 1997;25(3-4):351-6. (PMID: 9358909) ; Arch Orthop Trauma Surg. 2007 Feb;127(2):137-42. (PMID: 17053946) ; J Ethnopharmacol. 2018 Sep 15;223:76-87. (PMID: 29783019) ; Naunyn Schmiedebergs Arch Pharmacol. 2014 Nov;387(11):1025-36. (PMID: 25038619) Contributed Indexing: Keywords: BMP-2/Smad5/Runx2 pathway; Epimedium; alkaline phosphatase; rat bone mesenchymal stem cells Substance Nomenclature: 0 (Flavonoids) ; 104982-03-8 (Osteocalcin) ; EC 3.1.3.1 (Alkaline Phosphatase) ; VNM47R2QSQ (icariin) Entry Date(s): Date Created: 20210913 Date Completed: 20220119 Latest Revision: 20220426 Update Code: 20240513 PubMed Central ID: PMC8439244

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Effects of icariin on the fracture healing in young and old rats and its mechanism.