Aberrant expression of miR-33a-3p/IGF2 in postmenopausal osteoporosis patients and its role and mechanism in osteoporosis.
Postmenopausal osteoporosis
hBMSCs
miR-33a-3p/IGF2 axis
Journal
Journal of orthopaedic surgery and research
ISSN: 1749-799X
Titre abrégé: J Orthop Surg Res
Pays: England
ID NLM: 101265112
Informations de publication
Date de publication:
06 Jul 2023
06 Jul 2023
Historique:
received:
09
03
2023
accepted:
26
05
2023
medline:
10
7
2023
pubmed:
7
7
2023
entrez:
6
7
2023
Statut:
epublish
Résumé
Postmenopausal osteoporosis (PMOP), the most frequent bone-related disease, is characterized by bone loss and fragile fractures, which is related to low bone density (BMD). This study aimed to illustrate the expression and mechanism of miR-33a-3p in osteoporosis. TargetScan and luciferase reporter assay were applied for verifying the relevance between miR-33a-3p and IGF2. Levels of miR-33a-3p, IGF2, Runx2, ALP and Osterix were checked using RT-qPCR and western blotting. hBMSCs proliferation, apoptosis and ALP activity were analyzed by MTT, flow cytometry (FCM) analysis and ALP detection kit, respectively. Moreover, the calcification of cells was assessed using Alizarin Red S staining. The average BMD was evaluated by dual-energy X-ray absorptiometry (DEXA) assay. IGF2 was a target of miR-33a-3p. The level of miR-33a-3p was substantially higher and IGF2 expression was memorably lower in the serum of osteoporosis patients than that in healthy volunteers. Our results also pointed out that miR-33a-3p was reduced and IGF2 expression was enhanced during osteogenic differentiation. We concluded that miR-33a-3p negatively regulated the level of IGF2 in hBMSCs. Besides, miR-33a-3p mimic inhibited the osteogenic differentiation of hBMSCs via inhibiting the level of Runx2, ALP and Osterix and decreasing ALP activity. IGF2 plasmid dramatically reversed the influence of miR-33a-3p mimic on IGF2 expression, hBMSCs proliferation and apoptosis, and osteogenic differentiation of hBMSCs. miR-33a-3p affected osteogenic differentiation of hBMSCs by targeting IGF2, indicating a potential use of miR-33a-3p as plasma biomarker and therapeutic target for postmenopausal osteoporosis.
Sections du résumé
BACKGROUND
BACKGROUND
Postmenopausal osteoporosis (PMOP), the most frequent bone-related disease, is characterized by bone loss and fragile fractures, which is related to low bone density (BMD). This study aimed to illustrate the expression and mechanism of miR-33a-3p in osteoporosis.
METHODS
METHODS
TargetScan and luciferase reporter assay were applied for verifying the relevance between miR-33a-3p and IGF2. Levels of miR-33a-3p, IGF2, Runx2, ALP and Osterix were checked using RT-qPCR and western blotting. hBMSCs proliferation, apoptosis and ALP activity were analyzed by MTT, flow cytometry (FCM) analysis and ALP detection kit, respectively. Moreover, the calcification of cells was assessed using Alizarin Red S staining. The average BMD was evaluated by dual-energy X-ray absorptiometry (DEXA) assay.
RESULTS
RESULTS
IGF2 was a target of miR-33a-3p. The level of miR-33a-3p was substantially higher and IGF2 expression was memorably lower in the serum of osteoporosis patients than that in healthy volunteers. Our results also pointed out that miR-33a-3p was reduced and IGF2 expression was enhanced during osteogenic differentiation. We concluded that miR-33a-3p negatively regulated the level of IGF2 in hBMSCs. Besides, miR-33a-3p mimic inhibited the osteogenic differentiation of hBMSCs via inhibiting the level of Runx2, ALP and Osterix and decreasing ALP activity. IGF2 plasmid dramatically reversed the influence of miR-33a-3p mimic on IGF2 expression, hBMSCs proliferation and apoptosis, and osteogenic differentiation of hBMSCs.
CONCLUSION
CONCLUSIONS
miR-33a-3p affected osteogenic differentiation of hBMSCs by targeting IGF2, indicating a potential use of miR-33a-3p as plasma biomarker and therapeutic target for postmenopausal osteoporosis.
Identifiants
pubmed: 37415192
doi: 10.1186/s13018-023-03883-6
pii: 10.1186/s13018-023-03883-6
pmc: PMC10326950
doi:
Substances chimiques
MicroRNAs
0
Core Binding Factor Alpha 1 Subunit
0
IGF2 protein, human
0
Insulin-Like Growth Factor II
67763-97-7
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
487Informations de copyright
© 2023. The Author(s).
Références
Shanghai Kou Qiang Yi Xue. 2017 Aug;26(4):353-357
pubmed: 29199325
Eur Rev Med Pharmacol Sci. 2020 Jul;24(14):7565
pubmed: 32744670
Eur Rev Med Pharmacol Sci. 2020 Jul;24(14):7577
pubmed: 32744682
Br Med Bull. 2022 Sep 22;143(1):46-56
pubmed: 35641234
Br Med Bull. 2020 May 15;133(1):79-94
pubmed: 32219416
J Biol Chem. 2011 Apr 8;286(14):12328-39
pubmed: 21324897
Acta Biochim Biophys Sin (Shanghai). 2018 Mar 1;50(3):273-280
pubmed: 29425279
Br Med Bull. 2019 Jun 19;130(1):137-147
pubmed: 31066454
Maturitas. 2005 Jul 16;51(3):246-53
pubmed: 15978968
Development. 2013 Jul;140(13):2755-64
pubmed: 23698347
Nutr Res Pract. 2021 Oct;15(5):579-590
pubmed: 34603606
Expert Rev Clin Pharmacol. 2021 Jan;14(1):105-119
pubmed: 33183112
Oncotarget. 2016 Jul 5;7(27):42461-42473
pubmed: 27285759
Animals (Basel). 2022 Mar 12;12(6):
pubmed: 35327115
Aging (Albany NY). 2021 Feb 17;13(5):6945-6956
pubmed: 33621956
Mol Cell Probes. 2020 Feb;49:101479
pubmed: 31706013
J Orthop Surg Res. 2021 Aug 27;16(1):533
pubmed: 34452621
Prz Menopauzalny. 2014 Sep;13(4):213-20
pubmed: 26327857
J Orthop Surg Res. 2021 May 31;16(1):351
pubmed: 34059108
Stem Cell Res Ther. 2021 Jan 6;12(1):7
pubmed: 33407847
Aging (Albany NY). 2020 May 19;12(10):9500-9514
pubmed: 32427128
Front Pharmacol. 2018 Jun 29;9:687
pubmed: 30013477
Biomed Res Int. 2020 Sep 26;2020:4243015
pubmed: 33029507
BMC Cell Biol. 2010 Jun 23;11:44
pubmed: 20573191
Acta Biochim Pol. 2022 May 26;69(2):349-355
pubmed: 35617351
Br Med Bull. 2021 Jun 10;138(1):58-67
pubmed: 33454750
Folia Histochem Cytobiol. 2020;58(1):9-16
pubmed: 32176315
Mol Med Rep. 2020 Jan;21(1):43-50
pubmed: 31746352
Int J Gen Med. 2021 Nov 16;14:8341-8353
pubmed: 34815706
Br Med Bull. 2022 Jul 9;142(1):34-43
pubmed: 35488320
Cell Death Dis. 2021 Mar 4;12(3):245
pubmed: 33664256
J Orthop Surg Res. 2021 May 18;16(1):318
pubmed: 34006294
Fertil Steril. 2019 Nov;112(5):791-798
pubmed: 31731933
J Clin Endocrinol Metab. 2018 Mar 1;103(3):1206-1213
pubmed: 29309589
Osteoporos Int. 2019 Aug;30(8):1581-1589
pubmed: 31115592
Aging Cell. 2021 Jul;20(7):e13367
pubmed: 34101965