The influence of aging on osteoblast differentiation of human bone marrow mesenchymal stem cells

Bone ◽  
2011 ◽  
Vol 48 ◽  
pp. S104-S105
Author(s):  
L.S. Bellesini ◽  
F.S. Oliveira ◽  
P.T. De Oliveira ◽  
M.M. Beloti ◽  
A.L. Rosa⁎
Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 271
Author(s):  
Shan Liu ◽  
Zhuo-Hui Luo ◽  
Gui-Mei Ji ◽  
Wei Guo ◽  
Jia-Zhong Cai ◽  
...  

Cajanolactone A (CLA) is a stilbenoid discovered by us from Cajanus cajan (L.) Millsp. In our study, CLA was found to promote osteoblast differentiation in human bone marrow mesenchymal stem cells (hBMSCs), as judged by increased cellular alkaline phosphatase activity and extracellular calcium deposits, and elevated protein expression of Runx2, collagen-1, bone morphogenetic protein-2, and osteopontin. Mechanistic studies revealed that hBMSCs undergoing osteoblast differentiation expressed upregulated mRNA levels of Wnt3a, Wnt10b, LRP5/6, Frizzled 4, β-catenin, Runx2, and Osterix from the early stage of differentiation, indicating the role of activated Wnt/β-catenin signaling pathway in osteoblast differentiation. Addition of CLA to the differentiation medium further increased the mRNA level of Wnt3a, Wnt10b, Frizzled 4, LRP5, and β-catenin, inferring that CLA worked by stimulating Wnt/LRP5/β-catenin signaling. Wnt inhibitor dickkopf-1 antagonized CLA-promoted osteoblastogenesis, indicating that CLA did not target the downstream of canonical Wnt signaling pathway. Treatment with CLA caused no changes in mRNA expression level, as well as protein secretion of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL), indicating that CLA did not affect the OPG/RANKL axis. Our results showed that CLA, which promoted osteoblast differentiation in hBMSCs, through activating Wnt/LRP5/β-catenin signaling transduction, is a promising anti-osteoporotic drug candidate.


2021 ◽  
Author(s):  
Xia Yi ◽  
Ping Wu ◽  
Jianyun Liu ◽  
Shan He ◽  
Ying Gong ◽  
...  

Adipogenesis and osteoblastogenesis (adipo-osteoblastogenesis) are closely related processes involving with the phosphorylation of numerous cytoplasmic proteins and key transcription factors.


2012 ◽  
Vol 7 (6) ◽  
pp. 757-767 ◽  
Author(s):  
Sarah L Boddy ◽  
Wei Chen ◽  
Ricardo Romero-Guevara ◽  
Lucksy Kottam ◽  
Illaria Bellantuono ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Feng Zhi ◽  
Yi Ding ◽  
Rong Wang ◽  
Yujiao Yang ◽  
Kaiming Luo ◽  
...  

Abstract Background As one of the most common chronic diseases in the world, osteoporosis occurs especially in postmenopausal women. Circular RNAs (circRNAs) are emerging as major drivers in human disease. The aim of the present study was to analyse circRNA expression profiles in osteoporosis and to explore the clinical significance and the regulatory molecular mechanism of hsa_circ_0006859 during osteoporosis. Methods Exosomes were isolated from clinically collected serum samples. A circRNA microarray was performed to screen differentially expressed circRNAs. Quantitative real-time PCR (qRT-PCR) and western blot were performed to analyse target gene mRNA expression and protein expression. Alizarin red staining (ARS) was performed to evaluate the mineralization ability of human bone marrow mesenchymal stem cells (hBMSCs). Oil Red O staining was performed to evaluate the lipid droplet formation ability of hBMSCs. Bioinformatics analysis and the luciferase reporter assay were performed to investigate the interaction between two genes. Results Hsa_circ_0006859 was identified as one of the most upregulated circRNAs in the microarray analysis. Hsa_circ_0006859 in exosomes was upregulated in osteoporosis patients compared to healthy controls. Hsa_circ_0006859 differentiated osteopenia or osteoporosis patients from healthy controls with high sensitivity and specificity. Hsa_circ_0006859 suppressed osteoblastic differentiation and promoted adipogenic differentiation of hBMSCs. Hsa_circ_0006859 directly bound to miR-431-5p, and ROCK1 was identified as a novel target gene of miR-431-5p. Hsa_circ_0006859 is a competing endogenous RNA (ceRNA) of miR-431-5p that promotes ROCK1 expression. Hsa_circ_0006859 suppressed osteogenesis and promoted adipogenesis by sponging miR-431-5p to upregulate ROCK1. Conclusions Exosomal hsa_circ_0006859 is a potential biomarker for postmenopausal osteoporosis and controls the balance between osteogenesis and adipogenesis in hBMSCs by sponging miR-431-5p.


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