scholarly journals Increased BMPR1A Expression Enhances the Adipogenic Differentiation of Mesenchymal Stem Cells in Patients with Ankylosing Spondylitis

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Zhenhua Liu ◽  
Peng Wang ◽  
Shuizhong Cen ◽  
Liangbin Gao ◽  
Zhongyu Xie ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Ankylosing Spondylitis ◽  
Signaling Pathway ◽  
Adipogenic Differentiation ◽  
Marrow Fat ◽  
Differentiation Capacity ◽  
Bone Marrow Fat ◽  
Healthy Donors

Objective. To investigate the adipogenic differentiation capacity of mesenchymal stem cells (MSCs) from ankylosing spondylitis (AS) patients and explore the mechanism of abnormal MSC adipogenesis in AS. Methods. MSCs from patients with AS (ASMSCs) and healthy donors (HDMSCs) were cultured in adipogenic differentiation medium for up to 21 days. Adipogenic differentiation was determined using oil red O (ORO) staining and quantification and was confirmed by assessing adipogenic marker expression (PPAR-γ, FABP4, and adiponectin). Gene expression of adipogenic markers was detected using qRT-PCR. Protein levels of adipogenic markers and signaling pathway-related molecules were assessed via Western blotting. Levels of bone morphogenetic proteins 4, 6, 7, and 9 were determined using enzyme-linked immunosorbent assays. Lentiviruses encoding short hairpin RNAs (shRNAs) were constructed to reverse abnormal bone morphogenetic protein receptor 1A (BMPR1A) expression and evaluate its role in abnormal ASMSC adipogenic differentiation. Bone marrow fat content was assessed using hematoxylin and eosin (HE) staining. BMPR1A expression in bone marrow MSCs was measured using immunofluorescence staining. Results. ASMSCs exhibited a greater adipogenic differentiation capacity than HDMSCs. During adipogenesis, ASMSCs expressed BMPR1A at higher levels, which activated the BMP-pSmad1/5/8 signaling pathway and increased adipogenesis. BMPR1A silencing using an shRNA eliminated the difference in adipogenic differentiation between HDMSCs and ASMSCs. Moreover, HE and immunofluorescence staining showed higher bone marrow fat content and BMPR1A expression in patients with AS than in healthy donors. Conclusion. Increased BMPR1A expression induces abnormal ASMSC adipogenic differentiation, potentially contributing to fat metaplasia and thus new bone formation in patients with AS.

scholarly journals The BMP signaling pathway enhances the osteoblastic differentiation of bone marrow mesenchymal stem cells in rats with osteoporosis

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Bin Zhao ◽  
Gengyan Xing ◽  
Aiyuan Wang
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Signaling Pathway ◽  
Adipogenic Differentiation ◽  
Osteoblastic Differentiation ◽  
Bmp Signaling ◽  
Blank Group ◽  
Expression Levels ◽  
Marrow Mesenchymal Stem Cells

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.

Induction of neural-like differentiation in human mesenchymal stem cells derived from bone marrow, fat, spleen and thymus

Bone ◽  
2007 ◽  
Vol 40 (2) ◽  
pp. 382-390 ◽  
Author(s):  
Mauro Krampera ◽  
Silvia Marconi ◽  
Annalisa Pasini ◽  
Mirco Galiè ◽  
Gino Rigotti ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Marrow Fat ◽  
Bone Marrow Fat

scholarly journals Osteogenic/Adipogenic Imbalance in Bone Marrow Nestin+ mesenchymal Stem Cells in Patients with Chronic Graft-Versus-Host Disease

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5007-5007
Author(s):  
Hanzhou Qi ◽  
Haiyan Zhang ◽  
Kaibo Yang ◽  
Yanqiu Chen ◽  
Hua Jin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Graft Versus Host Disease ◽  
Adipogenic Differentiation ◽  
Bone Marrow Niche ◽  
Host Disease ◽  
Differentiation Capacity ◽  
Relative Expression ◽  
Graft Versus Host

Background: Chronic graft-versus-host disease (cGVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The roles of bone marrow niche in cGVHD pathogenesis have gained increasing attention in recent years. Nestin+ mesenchymal stem cells (MSCs) is an important component of bone marrow niche. However, the potential implication of Nestin+ MSCs in the pathophysiology of cGVHD has not been completely clarified. Methods: A total of 68 patients with hematologic malignancies who underwent allo-HSCT at Nanfang Hospital between April 2016 and October 2018 were enrolled in this experimental study. We analyzed expanded Nestin+ MSCs from patients with cGVHD and compared them with patients without cGVHD. The diagnosis and grade of cGVHD was made at the time of sample collection according to National Institutes of Health criteria (Howard M.S. et. al. BBMT 2015). The results were compared using one-way ANOVA and unpaired two-tailed Student t-test. Statistical significance was defined as P value of <.05. Result: The Nestin+ MSCs from both groups showed similar morphology, immunophenotype, proliferation, and apoptosis. However, the adipogenic differentiation capacity of Nestin+ MSCs in patients with cGVHD was significantly reduced compared with patients without cGVHD (relative expression of PPARγ 2.22±0.27, and 6.82±0.87, respectively, P<0.05). The osteogenic differentiation capacity was significantly increased in patients with cGVHD (relative expression of RUNX2 3.84±0.38, and 1.95±0.52, respectively, P<0.05)(Figure 1A,B). These abnormal differentiations were more significant in patients with moderate/severe cGVHD. Furthermore, β-catenin phosphorylation decreased and nuclear β-catenin increased in the Nestin+ MSCs of cGVHD patients(Figure 1 C). Conclusion: These results demonstrate that Nestin+ MSCs from cGVHD patients had abnormal differentiation characterized by decreased adipogenic differentiation capacity and enhanced osteogenic capacity. The reduction of phosphorylation of β-catenin play an important role in these abnormal differentiations. Disclosures No relevant conflicts of interest to declare.

Effect of Sirtuin1 (Sirt1) on Bone Marrow Mesenchymal Stem Cells (BMSCs) Osteogenesis/Adipogenesis via β-Catenin/The Transcription Factor T Cell Factor 1 (TCF1)/Runt-Related Transcription Factor 2 (RUNX2)

2021 ◽  
Vol 11 (10) ◽  
pp. 2070-2075
Author(s):  
Wenji Shi ◽  
Mingxing Zhao ◽  
Guangxia Shi
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Adipogenic Differentiation ◽  
Sham Operation ◽  
Runx2 Expression ◽  
Sham Operation Group ◽  
Marrow Mesenchymal Stem Cells ◽  
Operation Group ◽  
Sirna Group

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.

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 ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Adipogenic Differentiation ◽  
Marrow Mesenchymal Stem Cells
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