Effects of macrophages and CXCR2 on adipogenic differentiation of bone marrow mesenchymal stem cells

2018 ◽  
Vol 234 (6) ◽  
pp. 9475-9485 ◽  
Author(s):  
Dingding Cao ◽  
Feifei Ma ◽  
Shengrong Ouyang ◽  
Zhuo Liu ◽  
Yuanyuan Li ◽  
...  
2021 ◽  
Vol 11 (10) ◽  
pp. 2070-2075
Author(s):  
Wenji Shi ◽  
Mingxing Zhao ◽  
Guangxia Shi

Bone marrow mesenchymal stem cells (BMSCs) have self-renewal potential. Sirt1 regulates cell differentiation and apoptosis. However, Sirt1’s effect on BMSCs osteogenic/adipogenic differentiation has not been fully elucidated. SD rats were randomly divided into Osteoporosis (OP) group and sham operation group. OP rat BMSCs were isolated and assigned into control group, NC group and Sirt1 siRNA group followed by analysis of Sirt1 level by Real-time PCR, cell proliferation by MTT assay, expression of OC, OPN and FABP4 level by real time PCR, and β-Catenin/TCF1/Runx2 protein expression by Western blot. In OP group, Sirt1 expression was significantly increased and BMSCs proliferation was decreased along with reduced OC and OPN mRNA expression, increased FABP4 expression and reduced β-Catenin/TCF1/Runx2 expression compared with sham operation group (P < 0.05). In Sirt1 siRNA group, Sirt1 expression was significantly reduced, BMSCs proliferation was increased, OC and OPN mRNA expression was increased, FABP4 expression was decreased, and β-Catenin/TCF1/Runx2 expression was increased compared to OP group (P < 0.05). Sirt1 is increased in osteoporosis. Down-regulating Sirt1 in osteoporotic BMSCs can regulate β-Catenin/TCF1/Runx2 signaling and promote BMSCs osteogenic differentiation and inhibit adipogenic differentiation.


PLoS ONE ◽  
2012 ◽  
Vol 7 (3) ◽  
pp. e32481 ◽  
Author(s):  
Elisa Monaco ◽  
Massimo Bionaz ◽  
Sandra Rodriguez-Zas ◽  
Walter L. Hurley ◽  
Matthew B. Wheeler

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Meng Yang ◽  
Xin Yan ◽  
Fu-Zhen Yuan ◽  
Jing Ye ◽  
Ming-Ze Du ◽  
...  

Cartilage injury of the knee joint is very common. Due to the limited self-healing ability of articular cartilage, osteoarthritis is very likely to occur if left untreated. Bone marrow mesenchymal stem cells (BMMSCs) are widely used in the study of cartilage injury due to their low immunity and good amplification ability, but they still have disadvantages, such as heterogeneous undifferentiated cells. MicroRNAs can regulate the chondrogenic differentiation ability of MSCs by inhibiting or promoting mRNA translation and degradation. In this research, we primarily investigated the effect of microRNA-210-3p (miR-210-3p) on chondrogenic and adipogenic differentiation of BMMSCs in vitro. Our results demonstrate that miR-210-3p promoted chondrogenic differentiation and inhibited adipogenic differentiation of rat BMMSCs, which was related to the HIF-3α signalling pathway. Additionally, miR-210-3p promotes mRNA and protein levels of the chondrogenic expression genes COLII and SOX9 and inhibits mRNA and protein levels of the adipogenic expression genes PPARγ and LPL. Thus, miR-210-3p combined with BMMSCs is a candidate for future clinical applications in cartilage regeneration and could represent a promising new therapeutic target for OA.


2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Bin Zhao ◽  
Gengyan Xing ◽  
Aiyuan Wang

Abstract Background This study was conducted with the aim of exploring the effect of the BMP signaling pathway on osteoblastic differentiation in rat bone marrow mesenchymal stem cells (rBMSCs) in rats with osteoporosis (OP). Methods The bilateral ovaries of female SD rats were resected for the establishment of a rat OP model. The osteoblastic differentiation of isolated rBMSCs was identified through osteogenic induction. Adipogenetic induction and flow cytometry (FCM) were used to detect adipogenic differentiation and the expression of rBMSC surface markers. The rBMSCs were grouped into the blank group, NC group, si-BMP2 group, and oe-BMP2 group. The expression levels of key factors and osteogenesis-related factors were determined by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). The formation of calcified nodules was observed by alizarin red staining. ALP activity was measured by alkaline phosphatase staining. Results The rats with OP had greater weight but decreased bone mineral density (BMD) than normal rats (all P < 0.01). The rBMSCs from rats with OP were capable of osteoblastic differentiation and adipogenic differentiation and showed high expression of CD44 (91.3 ± 2.9%) and CD105 (94.8 ± 2.1%). Compared with the blank group, the oe-BMP2 group had elevated BMP-2 and Smad1 levels and an increase in calcified nodules and ALP-positive staining areas (all P < 0.05). Moreover, the expression levels of Runx2, OC, and OPN in the oe-BMP2 group were relatively higher than those in the blank group (all P < 0.05). The findings in the si-BMP2 group were opposite to those in the oe-BMP2 group. Conclusion BMP signaling pathways activated by BMP-2 can promote the osteoblastic differentiation of rBMSCs from rats with OP.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5064-5064
Author(s):  
Mitra Azadniv ◽  
Jason R. Myers ◽  
Helene McMurray ◽  
John M. Ashton ◽  
Naxin Guo ◽  
...  

Abstract Background: Bone marrow mesenchymal stem cells (BMSCs) constitute one of the important cellular components of the hematopoietic microenvironmental niche. These cells are capable of differentiation into osteoprogenitors which comprise part of the endosteal niche. In vivo studies have shown that depletion of BMSCs resulted in reduction of hematopoietic stem cell content, and there is direct in vitro evidence that BMSCs are able to support both normal and leukemia progenitor cell proliferation and survival and contribute to leukemia cell resistance to cytotoxic therapies. Whether BMSCs from leukemia marrow differ from normal counterparts and how they contribute to and are influenced by the leukemia environmental niche are still incompletely understood. In this work we sought to compare normal and AML-derived BMSCs and to define the propensity of BMSCs from leukemia patients for osteogenic or adipogenic differentiation. Methods: BMSCs were isolated from marrow aspirates of normal donor and AML patients using standard methodologies. Donors were age-matched to the leukemia patients to the extent possible in each comparative experiment. Such cells met the definition of MSCs in that they were adherent and expressed CD73, CD90, CD44, CD117 and CD105 and had osteoblastic and adipogenic differentiation capabilities. All comparisons were done at comparable passage number between samples. Results: BMSCs from AML donors demonstrated irregular vs. spindle shaped morphology as compared with BMSCs from younger donors <50 years of age but similar morphology to those grown from older donors. AML derived BMSCs were larger and had slower growth rate as assessed by longer passage times during lower passages (41 vs. 21 days). Cell surface expression markers were similar between normal and AML. CFU-F outgrowth was less from AML as compared to normal BMSC, and no difference in osteogenic differentiation was noted by Alizarin Red S measurement. On the other hand, lipid droplet formation measured by Oil Red O during adipogenic differentiation induction was greater in the AML BMSCs as compared with age matched controls, suggesting increased adipogenic differentiation potential. To determine if we could detect a gene signature difference between AML and normal BMSCs which would predict adipogenic propensity, RNA-Seq analysis was performed on AML and normal donor specimens(n=3 in each group), all from subjects >50 years of age using CuffDiff (v2.0.2). This identified 88 genes differentially expressed between the two groups. A heat map was generated using Euclidean distance hierarchical clustering of gene expression values from individual samples. This readily grouped AML vs. normal samples. Pathway analysis using Ingenuity Pathway Analysis (IPA) predicted dysregulation of four canonical pathways in AML-BMSCs as compared to normal BMSCs. These included 1) Role of tissue factor in cancer, 2) Airway pathology in COPD, 3) Oleate biosynthesis, and 4) Adipogenesis. The last two pathways are consistent with the biological observation of enhanced adipogenesis in AML-derived BMSCs. IPA analysis proposed a model of altered adipogenic differentiation in AML-BMSCs attributable to lower expression of two key regulatory genes, SOX9 and EGR2. Reduced expression of SOX9 and EGR2 in AML BMSCs as compared to normal BMSCs was validated by qRT-PCR and western blot analysis. SOX9 is reported to contribute to the commitment of MSCs to adipogenic phenotype through negative influence on expression of key transcription factors in adipogenesis, and ERG2 downregulation is required in some systems for adipocyte lineage commitment. Conclusion: Understanding the role that adipogenic MSCs play during leukemia evolution and treatment could offer insight into pathogenesis and potential therapies for these disorders. Disclosures Liesveld: Onconova: Other: Data safety monitoring board; Astex: Honoraria; glycomimetics: Research Funding.


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