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Background: Icariin, a traditional Chinese medicine, has demonstrated anti-osteoporotic properties in ovariectomized mice. However, its effectiveness in preventing bone loss induced by ketogenic diet (KD), which mimics osteoporosis in human, remains unexplored. This study aims to investigate icariin's impact on KD-induced bone loss in mice.

Methods: Thirty mice were divided into: sham, KD, and KD + icariin groups. Post a 12-week intervention, evaluation including bone microstructures, serum concentrations of tartrate-resistant acid phosphatase (TRAP) and bone-specific alkaline phosphatase (ALP), and femoral tissue expression levels of osteocalcin (OCN) and TRAP. The expression levels of mammalian target of rapamycin (mTOR), ALP, peroxisome proliferator-activated receptor gamma (PPAR-γ), phosphorylated mTOR (p-mTOR), and the autophagy adaptor protein (p62) were also analyzed. Alizarin granule deposition and cellular ALP levels were measured following the induction of bone marrow mesenchymal stem cells (BMSCs) into osteogenesis.

Results: The study found that KD significantly impaired BMSCs' osteogenic differentiation, leading to bone loss. Icariin notably increased bone mass, stimulated osteogenesis, and reduced cancellous bone loss. In the KD + icariin group, measures such as bone tissue density (TMD), bone volume fraction (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th) were significantly higher than in the KD group. Additionally, bone trabecular separation (Tb.Sp) was markedly lower in the KD + icariin group. Moreover, icariin increased OCN and ALP levels while suppressing PPAR-γ, TRAP, p62, and p-mTOR. In cellular studies, icariin encouraged osteogenic development in BMSCs under KD conditions.

Conclusions: Icariin effectively counteracts bone thinning and improves bone microstructure. Its mechanism likely involves stimulating BMSCs osteogenic differentiation and inhibiting bone resorption, potentially through mTOR downregulation. These findings suggest icariin's potential as an alternative treatment for KD-induced bone loss.

Titel:	Icariin promotes bone marrow mesenchymal stem cells osteogenic differentiation via the mTOR/autophagy pathway to improve ketogenic diet-associated osteoporosis.
Autor/in / Beteiligte Person:	Liu, W ; Xiang, S ; Wu, Y ; Zhang, D ; Xie, C ; Hu, H ; Liu, Q
Link:	Zum Volltext
Zeitschrift:	Journal of orthopaedic surgery and research, Jg. 19 (2024-02-07), Heft 1, S. 127
Veröffentlichung:	London : BioMed Central, 2006-, 2024
Medientyp:	academicJournal
ISSN:	1749-799X (electronic)
DOI:	10.1186/s13018-024-04529-x
Schlagwort:	Humans Mice Animals Osteogenesis Peroxisome Proliferator-Activated Receptors metabolism Peroxisome Proliferator-Activated Receptors pharmacology Cell Differentiation TOR Serine-Threonine Kinases metabolism Autophagy Bone Marrow Cells metabolism Cells, Cultured Mammals Diet, Ketogenic Osteoporosis drug therapy Osteoporosis etiology Osteoporosis metabolism Bone Diseases, Metabolic metabolism Mesenchymal Stem Cells metabolism Flavonoids
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [J Orthop Surg Res] 2024 Feb 07; Vol. 19 (1), pp. 127. <i>Date of Electronic Publication: </i>2024 Feb 07. MeSH Terms: Diet, Ketogenic* ; Osteoporosis* / drug therapy ; Osteoporosis* / etiology ; Osteoporosis* / metabolism ; Bone Diseases, Metabolic* / metabolism ; Mesenchymal Stem Cells* / metabolism ; Flavonoids* ; Humans ; Mice ; Animals ; Osteogenesis ; Peroxisome Proliferator-Activated Receptors / metabolism ; Peroxisome Proliferator-Activated Receptors / pharmacology ; Cell Differentiation ; TOR Serine-Threonine Kinases / metabolism ; Autophagy ; Bone Marrow Cells / metabolism ; Cells, Cultured ; Mammals References: J Clin Med. 2022 Dec 16;11(24):. (PMID: 36556093) ; Bone Res. 2019 Oct 3;7:28. (PMID: 31666998) ; Br Med Bull. 2022 Sep 22;143(1):46-56. (PMID: 35641234) ; Nutrients. 2021 May 13;13(5):. (PMID: 34068325) ; Best Pract Res Clin Endocrinol Metab. 2018 Oct;32(5):725-738. (PMID: 30449551) ; Calcif Tissue Int. 2019 Jan;104(1):59-69. (PMID: 30167745) ; Int J Mol Sci. 2015 Mar 10;16(3):5452-66. (PMID: 25764158) ; J Orthop Surg Res. 2021 May 18;16(1):318. (PMID: 34006294) ; Osteoporos Int. 2018 Mar;29(3):535-544. (PMID: 29110063) ; Clin Biochem. 2022 Nov-Dec;109-110:1-10. (PMID: 36096182) ; J Orthop Surg Res. 2021 Aug 27;16(1):533. (PMID: 34452621) ; Bioengineered. 2021 Dec;12(1):2984-2999. (PMID: 34167449) ; J Nutr Biochem. 2010 Dec;21(12):1162-9. (PMID: 20149618) ; Exp Anim. 2019 Aug 14;68(3):371-380. (PMID: 30944267) ; J Orthop Surg Res. 2021 May 31;16(1):351. (PMID: 34059108) ; Osteoarthritis Cartilage. 2020 Apr;28(4):400-409. (PMID: 32081707) ; Lancet Diabetes Endocrinol. 2017 Nov;5(11):908-923. (PMID: 28689768) ; Comp Med. 2008 Oct;58(5):424-30. (PMID: 19004367) ; Morphologie. 2008 Dec;92(299):162-70. (PMID: 19019718) ; Int J Mol Sci. 2020 Oct 15;21(20):. (PMID: 33076329) ; Diabetes Metab Syndr Obes. 2021 Jun 17;14:2753-2764. (PMID: 34168475) ; Adv Pharmacol. 2020;87:179-203. (PMID: 32089233) ; Nat Cell Biol. 2011 Feb;13(2):132-41. (PMID: 21258367) ; Calcif Tissue Int. 2017 Oct;101(4):412-421. (PMID: 28547346) ; Lancet. 2022 Mar 12;399(10329):1080-1092. (PMID: 35279261) ; J Cell Physiol. 2013 Mar;228(3):513-21. (PMID: 22777826) ; J Cell Biochem. 2019 Aug;120(8):13121-13132. (PMID: 30887562) ; J Cell Physiol. 2018 May;233(5):3929-3944. (PMID: 28834576) ; Eur J Pharmacol. 2015 Jul 15;759:287-94. (PMID: 25814262) ; Exp Ther Med. 2017 May;13(5):2399-2404. (PMID: 28565854) ; J Nutr. 1997 May;127(5 Suppl):838S-841S. (PMID: 9164249) ; Int J Mol Sci. 2020 Jan 05;21(1):. (PMID: 31948061) ; Medicina (Kaunas). 2021 Oct 17;57(10):. (PMID: 34684156) ; Life Sci. 2016 Feb 15;147:46-58. (PMID: 26796578) ; Expert Rev Clin Pharmacol. 2021 Jan;14(1):105-119. (PMID: 33183112) ; Calcif Tissue Int. 2014 Jan;94(1):78-87. (PMID: 24101233) ; Life Sci. 2015 Apr 1;126:57-68. (PMID: 25634110) Contributed Indexing: Keywords: Autophagy; Icariin; Ketogenic diet; Osteoporosis; mTOR Substance Nomenclature: VNM47R2QSQ (icariin) ; 0 (Peroxisome Proliferator-Activated Receptors) ; EC 2.7.11.1 (TOR Serine-Threonine Kinases) ; 0 (Flavonoids) Entry Date(s): Date Created: 20240207 Date Completed: 20240209 Latest Revision: 20240210 Update Code: 20240210 PubMed Central ID: PMC10851475

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Icariin promotes bone marrow mesenchymal stem cells osteogenic differentiation via the mTOR/autophagy pathway to improve ketogenic diet-associated osteoporosis.