scholarly journals Chondrogenic Differentiation Processes in Human Bone-Marrow Aspirates Seeded in Three-Dimensional-Woven Poly(ɛ-Caprolactone) Scaffolds Enhanced by Recombinant Adeno-Associated Virus–MediatedSOX9Gene Transfer

2018 ◽  
Vol 29 (11) ◽  
pp. 1277-1286 ◽  
Author(s):  
Jagadeesh K. Venkatesan ◽  
Franklin T. Moutos ◽  
Ana Rey-Rico ◽  
Bradley T. Estes ◽  
Janina Frisch ◽  
...  
2019 ◽  
Vol 235 (4) ◽  
pp. 3497-3507
Author(s):  
Eve Salonius ◽  
Leena Kontturi ◽  
Anita Laitinen ◽  
Anne‐Marie Haaparanta ◽  
Matti Korhonen ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Guping Mao ◽  
Yiyang Xu ◽  
Dianbo Long ◽  
Hong Sun ◽  
Hongyi Li ◽  
...  

Abstract Objectives Aberrations in exosomal circular RNA (circRNA) expression have been identified in various human diseases. In this study, we investigated whether exosomal circRNAs could act as competing endogenous RNAs (ceRNAs) to regulate the pathological process of osteoarthritis (OA). This study aimed to elucidate the specific MSC-derived exosomal circRNAs responsible for MSC-mediated chondrogenic differentiation using human bone marrow-derived MSCs (hMSCs) and a destabilization of the medial meniscus (DMM) mouse model of OA. Methods Exosomal circRNA deep sequencing was performed to evaluate the expression of circRNAs in human bone marrow-derived MSCs (hMSCs) induced to undergo chondrogenesis from day 0 to day 21. The regulatory and functional roles of exosomal circRNA_0001236 were examined on day 21 after inducing chondrogenesis in hMSCs and were validated in vitro and in vivo. The downstream target of circRNA_0001236 was also explored in vitro and in vivo using bioinformatics analyses. A luciferase reporter assay was used to evaluate the interaction between circRNA_0001236 and miR-3677-3p as well as the target gene sex-determining region Y-box 9 (Sox9). The function and mechanism of exosomal circRNA_0001236 in OA were explored in the DMM mouse model. Results Upregulation of exosomal circRNA_0001236 enhanced the expression of Col2a1 and Sox9 but inhibited that of MMP13 in hMSCs induced to undergo chondrogenesis. Moreover, circRNA_0001236 acted as an miR-3677-3p sponge and functioned in human chondrocytes via targeting miR-3677-3p and Sox9. Intra-articular injection of exosomal circRNA_0001236 attenuated OA in the DMM mouse model. Conclusions Our results reveal an important role for a novel exosomal circRNA_0001236 in chondrogenic differentiation. Overexpression of exosomal circRNA_0001236 promoted cartilage-specific gene and protein expression through the miR-3677-3p/Sox9 axis. Thus, circRNA_0001236-overexpressing exosomes may alleviate cartilage degradation, suppressing OA progression and enhancing cartilage repair. Our findings provide a potentially effective therapeutic strategy for treating OA.


PLoS ONE ◽  
2016 ◽  
Vol 11 (12) ◽  
pp. e0168173 ◽  
Author(s):  
Birte S. Steiniger ◽  
Vitus Stachniss ◽  
Verena Wilhelmi ◽  
Anja Seiler ◽  
Katrin Lampp ◽  
...  

2021 ◽  
Vol 41 ◽  
pp. 603-615
Author(s):  
A-N Zeller ◽  
◽  
M Selle ◽  
Z Gong ◽  
M Winkelmann ◽  
...  

Underlying pathomechanisms of osteoporosis are still not fully elucidated. Cell-based therapy approaches pose new possibilities to treat osteoporosis and its complications. The aim of this study was to quantify differences in human bone marrow-derived mesenchymal stem cells (hBMSCs) between healthy donors and those suffering from clinically manifest osteoporosis. Cell samples of seven donors for each group were selected retrospectively from the hBMSC cell bank of the Trauma Department of Hannover Medical School. Cells were evaluated for their adipogenic, osteogenic and chondrogenic differentiation potential, for their proliferation potential and expression of surface antigens. Furthermore, a RT2 Osteoporosis Profiler PCR array, as well as quantitative real-time PCR were carried out to evaluate changes in gene expression. Cultivated hBMSCs from osteoporotic donors showed significantly lower cell surface expression of CD274 (4.98 % ± 2.38 %) than those from the control group (26.03 % ± 13.39 %; p = 0.007), as assessed by flow cytometry. In osteoporotic patients, genes involved in inhibition of the anabolic WNT signalling pathway and those associated with stimulation of bone resorption were significantly upregulated. Apart from these changes, no significant differences were found for the other cell surface antigens, adipogenic, osteogenic and chondrogenic differentiation ability as well as proliferation potential. These findings supported the theory of an influence of CD274 on the regulation of bone metabolism. CD274 might be a promising target for further investigations of the pathogenesis of osteoporosis and of cell-based therapies involving MSCs.


2020 ◽  
Vol 26 (7-8) ◽  
pp. 450-459 ◽  
Author(s):  
Jagadeesh K. Venkatesan ◽  
Céline Falentin-Daudré ◽  
Amélie Leroux ◽  
Véronique Migonney ◽  
Magali Cucchiarini

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