Int J Sports Med
DOI: 10.1055/a-2323-9749
Orthopedics & Biomechanics
1
Histology & Embryology Teaching and Researching Section, Xi’an
Medical University, Xi’an, China
,
Mingjuan Shi
2
Public Health College, Xi’an Medical University, Xi’an,
China
,
Xuan Zhao
1
Histology & Embryology Teaching and Researching Section, Xi’an
Medical University, Xi’an, China
,
Guifu Wu
3
Department Endocrinology, Shaanxi Province People Hospital, Xi’an,
China
,
Huiyuan Zheng
1
Histology & Embryology Teaching and Researching Section, Xi’an
Medical University, Xi’an, China
,
Yuanyuan Cui
1
Histology & Embryology Teaching and Researching Section, Xi’an
Medical University, Xi’an, China
,
Yu Shang
4
Clinical College, Xi’an Medical University, Xi’an, China
› Author Affiliations
Funding Information
Shaanxi Science and Technology Department Fund Project — 2010K13-01-03
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Abstract
Osteogenic differentiation of human bone marrow-derived mesenchymal stem cells
(hBMSCs) is important for human bone formation. Long non-coding RNAs (lncRNAs)
are critical regulators in osteogenic differentiation. This study aimed to
explore the function and mechanisms of long intergenic non-protein coding RNA
963 (LINC00963) in affecting osteogenesis. Cell differentiation was assessed by
alkaline phosphatase (ALP) activity detection and ALP staining assay. Meanwhile,
levels of osteogenic marker genes, including RUNX family transcription factor 2
(RUNX2), osteocalcin (OCN), and osteopontin (OPN), were detected by RT-qPCR and
western blot. Cell proliferation and apoptosis were measured using CCK-8 assay
and flow cytometry analysis. RNA immunoprecipitation (RIP), RNA pull-down and
luciferase reporter assays were used to investigate the interaction between
genes. LINC00963 expression was down-regulated in hBMSCs treated with osteogenic
induction. LINC00963 overexpression inhibited hBMSCs differentiation,
proliferation, and elevated apoptosis. LINC00963 acted as a competing endogenous
RNA (ceRNA) to interact with miR-10b-5p and thereby regulated the expression
level of Ras-related protein Rap-2a (RAP2A). LINC00963 regulated RAP2A to
inhibit the level of phosphorylated AKT (p-AKT). LINC00963 inhibited hBMSCs
differentiation, proliferation, and elevated apoptosis via the
miR-10b-5p/RAP2A/AKT signaling, which might help improve the treatment of
osteoporosis.
Keywords
postmenopausal osteoporosis -
LINC00963 -
differentiation -
AKT
Publication History
Received: 22 August 2022
Accepted: 26 April 2024
Article published online:
28 July 2024
© 2024. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
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