scholarly journals 529 PARATHYROID HORMONE-RELATED PROTEIN (PTHRP) PROMOTES CHONDROGENIC DIFFERENTIATION OF BONE MARROW MESENCHYMAL STEM CELLS (BM-MSCS) GROWN ON TYPE I COLLAGEN SUPPORTS

2010 ◽  
Vol 18 ◽  
pp. S237-S238
Author(s):  
S. Diaz-Prado ◽  
C. Trejo-Iriarte ◽  
E. Muiños ◽  
D. Lozano ◽  
N. Garcia-Honduvilla ◽  
...  
2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Hongliang He ◽  
Xiaozhen Liu ◽  
Liang Peng ◽  
Zhiliang Gao ◽  
Yun Ye ◽  
...  

Interactions between stem cells and extracellular matrix (ECM) are requisite for inducing lineage-specific differentiation and maintaining biological functions of mesenchymal stem cells by providing a composite set of chemical and structural signals. Here we investigated if cell-deposited ECM mimickedin vivoliver's stem cell microenvironment and facilitated hepatogenic maturation. Decellularization process preserved the fibrillar microstructure and a mix of matrix proteins in cell-deposited ECM, such as type I collagen, type III collagen, fibronectin, and laminin that were identical to those found in native liver. Compared with the cells on tissue culture polystyrene (TCPS), bone marrow mesenchymal stem cells (BM-MSCs) cultured on cell-deposited ECM showed a spindle-like shape, a robust proliferative capacity, and a suppressed level of intracellular reactive oxygen species, accompanied with upregulation of two superoxide dismutases. Hepatocyte-like cells differentiated from BM-MSCs on ECM were determined with a more intensive staining of glycogen storage, an elevated level of urea biosynthesis, and higher expressions of hepatocyte-specific genes in contrast to those on TCPS. These results demonstrate that cell-deposited ECM can be an effective method to facilitate hepatic maturation of BM-MSCs and promote stem-cell-based liver regenerative medicine.


2020 ◽  
Vol 10 (2) ◽  
pp. 246-251
Author(s):  
Wenxiao Jiang ◽  
Yijun Zhang ◽  
Ye Huang ◽  
Yunfeng Cheng ◽  
Zhigang Liu

Hepatic kinase B1 (LKB1) is a tumor suppressor and regulates cell proliferation and apoptosis. However, whether LKB1 affects bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation of during aging remains unclear. Two BMSCs derived from Zempster24−/− (aging) and Zempster24+/+ (normal) mice were cultured in vitro followed by measurement of LKB1 expression by real-time quantitative PCR and Western blot. LKB1 siRNA was transfected into Zempster24−/−BMSCs and LKB1 expression was measured. 14 days after osteogenic induction, mineralized nodule formation was evaluated by alizarin red staining, expression of Calcin, type I collagen, RUNX2 and OPN mRNA expression was measured, together with alkaline phosphatase (ALP) activity and the PI3K/mTOR pathway activity. Compared with normal BMSCs, LKB1 expression was significantly increased, calcified nodules were decreased, with reduced expression of osteocalcin, type I collagen, RUNX2 and OPN mRNA as well as decreased ALP activity and PI3K/mTOR signaling protein expression (P < 0.05). LKB1 siRNA transfection into senescent BMSCs down-regulated LKB1 expression, increased calcification nodule formation, expression of osteocalcin, type I collagen, RUNX2 and OPN mRNA, as well as increased ALP activity and PI3K/mTOR pathway protein expression (P < 0.05). Aging can promote the increase of LKB1 expression and inhibit the osteogenic differentiation of BMSCs. Down-regulation of LKB1 expression in BMSCs during senescence can promote osteogenic differentiation through regulating PI3K/mTOR pathway.


2019 ◽  
Vol 9 (12) ◽  
pp. 1776-1782
Author(s):  
Yongyi Xu ◽  
Lei Chen

The distal low homeobox 3 (DLX3) regulates the bone marrow mesenchymal stem cells (BMSC) osteogenic differentiation. However, whether DLX3 affects osteoporosis (OP) remains unclear. An OVX-induced OP rat model was constructed and DLX3 plasmid was injected followed by analysis of bone mineral density and ALP activity. Rat BMSCs were isolated and divided into control group, OP group and DLX3 group (transfected with DLX3 plasmid) followed by analysis of chondrocytes survival rate by MTT assay, Caspase 3 activity, type I collagen and Osterix expression by Real time PCR and -catenin level by Western blot. DLX3 expression was significantly down-regulated in OP rats with deceased bone density and ALP activity compared to sham group (P < 0 05). When DLX3 was transfected into OP rats, DLX3 expression was significantly up-regulated with increased bone density and ALP activity compared with OP group (P < 0 05). BMSCs survival was significantly decreased in OP group and Caspase 3 activity was significantly increased with downregulated type I collagen, Osterix and -catenin (P < 0 05). However, transfection of DLX3 plasmid into OP group BMSCs cells can significantly reverse the above changes, compared to OP group (P < 0 05). DLX3 expression is reduced in osteoporosis. Up-regulation of DLX3 can promote osteogenic differentiation of BMSCs by regulating typical Wnt signaling, promote differentiation into osteoblasts, increase bone density increase, and then ameliorate osteoporosis.


Cartilage ◽  
2021 ◽  
pp. 194760352199321
Author(s):  
Stefania Pagani ◽  
Francesca Veronesi ◽  
Gianluca Giavaresi ◽  
Giuseppe Filardo ◽  
Tiziana Papio ◽  
...  

Objective Osteoarthritis (OA) is an inflammatory and degenerative disease, and the numerous treatments currently used are not fully effective. Mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) are proposed for OA treatment as biologic therapies. The aim of the study was to observe the role of autologous protein solution (APS), a type of PRP, on chondrogenic differentiation of 2 types of MSCs, from bone marrow (BMSCs) and adipose tissue (ADSCs), in an in vitro osteoarthritic microenvironment. Design Inflammatory culture conditions, mimicking OA, were obtained by adding interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα), or synovial fluid from patient osteoarthritic knees (OSF), to the culture medium. MSCs were then treated with APS. Results After 1 month of culture, both cell types formed mature micromasses, partially altered in the presence of IL-1β and TNFα but quite preserved with OSF. Inflammatory conditions hindered differentiation in terms of gene expression, not counterbalanced by APS. APS triggered type I collagen deposition and above all contributed to decrease the expression of metalloproteinases in the most aggressive conditions (IL-1β and TNFα in the culture medium). ADSCs originated micromasses more mature and less prone toward osteogenic lineage than BMSCs, thus showing to better adapt in an aggressive environment than BMSC. Conclusions APS seems to act better on inflammation front and, between cell types, ADSCs respond better to the inflammatory microenvironment of OA and to the treatment with APS than BMSCs.


2020 ◽  
Author(s):  
Xiaoling Zhang ◽  
Liangzhi Du ◽  
Ningbo Zhao ◽  
Lizhe Zhu ◽  
Lei Wang ◽  
...  

Abstract Background: In recent years, researchers have found that exosomes, an important component of intercellular signal transduction and exchange, have great significance in bone tissue repair. In this study, to further promote the development of oral implants, preliminary in vitro experiments were conducted to verify the different concentrations of exosomes from bone marrow mesenchymal stem cells (BMSC-exos) for osteogenesis on the surfaces of titanium sheets.Methods: In this experiment, rabbit bone marrow mesenchymal stem cells(BMSCs) were seeded on the surfaces of 10 mm × 10 mm × 1 mm square titanium sheets and were divided into four groups to investigate their adsorption, proliferation and osteogenesis after treatment with different concentrations of BMSC-exos: 1. BMSCs + titanium + 0 µg/ml BMSC-exos; 2. BMSCs + titanium + 10 µg/ml BMSC-exos; 3. BMSCs + titanium + 25 µg/ml BMSC-exos; and 4. BMSCs + titanium + 50 µg/ml BMSC-exos.Results: Compared with the control group, BMSCs’ adsorption, extension, proliferation and osteogenesis on titanium sheets were significantly increased in the Exosomes group.Conclusions: Exosomes can promote the bone formation of BMSCs on titanium plates by promoting adsorption, extension, proliferation, production of alkaline phosphatase(ALP) and type I collagen and mineralization during the osteogenesis process.


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