mir-150-5p inhibits the osteogenic differentiation of bone marrow-derived mesenchymal stem cells by targeting irisin to regulate the p38/MAPK signaling pathway

© 2024. The Author(s)..

PURPOSE: To study the effect of miR-150-5p on the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs), and further explore the relationship between its regulatory mechanism and irisin.

METHODS: We isolated mouse BMSCs, and induced osteogenic differentiation by osteogenic induction medium. Using qPCR to detect the expression of osteogenic differentiation-related genes, western blot to detect the expression of osteogenic differentiation-related proteins, and luciferase reporter system to verify that FNDC5 is the target of miR-150-5p. Irisin intraperitoneal injection to treat osteoporosis in mice constructed by subcutaneous injection of dexamethasone.

RESULTS: Up-regulation of miR-150-5p inhibited the proliferation of BMSCs, and decreased the content of osteocalcin, ALP activity, calcium deposition, the expression of osteogenic differentiation genes (Runx2, OSX, OCN, OPN, ALP and BMP2) and protein (BMP2, OCN, and Runx2). And down-regulation of miR-150-5p plays the opposite role of up-regulation of miR-150-5p on osteogenic differentiation of BMSCs. Results of luciferase reporter gene assay showed that FNDC5 gene was the target gene of miR-150-5p, and miR-150-5p inhibited the expression of FNDC5 in mouse BMSCs. The expression of osteogenic differentiation genes and protein, the content of osteocalcin, ALP activity and calcium deposition in BMSCs co-overexpressed by miR-150-5p and FNDC5 was significantly higher than that of miR-150-5p overexpressed alone. In addition, the overexpression of FNDC5 reversed the blocked of p38/MAPK pathway by the overexpression of miR-150-5p in BMSCs. Irisin, a protein encoded by FNDC5 gene, improved symptoms in osteoporosis mice through intraperitoneal injection, while the inhibitor of p38/MAPK pathway weakened this function of irisin.

CONCLUSION: miR-150-5p inhibits the osteogenic differentiation of BMSCs by targeting irisin to regulate the/p38/MAPK signaling pathway, and miR-150-5p/irisin/p38 pathway is a potential target for treating osteoporosis.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:19

Enthalten in:

Journal of orthopaedic surgery and research - 19(2024), 1 vom: 18. März, Seite 190

Sprache:

Englisch

Beteiligte Personen:

Qi, Jia-Long [VerfasserIn]
Zhang, Zhi-Dong [VerfasserIn]
Dong, Zhou [VerfasserIn]
Shan, Tao [VerfasserIn]
Yin, Zong-Sheng [VerfasserIn]

Links:

Volltext

Themen:

104982-03-8
Bone marrow-derived mesenchymal stem cells
Calcium
Core Binding Factor Alpha 1 Subunit
EC 1.13.12.-
EC 2.7.11.24
FNDC5 protein, mouse
Fibronectins
Irisin
Journal Article
Luciferases
MiR-150-5p
MicroRNAs
Mirn150 microRNA, mouse
Osteocalcin
Osteogenic differentiation
Osteoporosis
P38 Mitogen-Activated Protein Kinases
SY7Q814VUP
Transcription Factors

Anmerkungen:

Date Completed 20.03.2024

Date Revised 21.03.2024

published: Electronic

Citation Status MEDLINE

doi:

10.1186/s13018-024-04671-6

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM369898494