1,25-Dihydroxyvitamin D3 modulates the cross-talk between mesenchymal stem cells and macrophages

2014 ◽  
Author(s):  
Gema Valles ◽  
Fatima Bensiamar ◽  
Nuria Vilaboa ◽  
Laura Saldana
2014 ◽  
Vol 289 (1-2) ◽  
pp. 174-184 ◽  
Author(s):  
Nilda Sánchez ◽  
Alex Miranda ◽  
Juan M. Funes ◽  
Giselle Hevia ◽  
Rolando Pérez ◽  
...  

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Laura Saldaña ◽  
Gema Vallés ◽  
Fátima Bensiamar ◽  
Francisco José Mancebo ◽  
Eduardo García-Rey ◽  
...  

Abstract Mesenchymal stem cells (MSC) modulate the macrophage-mediated inflammatory response through the secretion of soluble factors. In addition to its classical effects on calcium homeostasis, 1,25-dihydroxyvitamin D3 (1,25D3) has emerged as an important regulator of the immune system. The present study investigates whether 1,25D3 modulates the paracrine interactions between MSC and macrophages. 1,25D3 stimulated MSC to produce PGE2 and VEGF and regulated the interplay between macrophages and MSC toward reduced pro-inflammatory cytokine production. Conditioned media (CM) from co-cultures of macrophages and MSC impaired MSC osteogenesis. However, MSC cultured in CM from 1,25D3-treated co-cultures showed increased matrix maturation and mineralization. Co-culturing MSC with macrophages prevented the 1,25D3-induced increase in RANKL levels, which correlated with up-regulation of OPG secretion. MSC seeding in three-dimensional (3D) substrates potentiated their immunomodulatory effects on macrophages. Exposure of 3D co-cultures to 1,25D3 further reduced the levels of soluble factors related to inflammation and chemotaxis. As a consequence of 1,25D3 treatment, the recruitment of monocytes toward CM of 3D co-cultures decreased, while the osteogenic maturation of MSC increased. These data add new insights into the pleiotropic effects of 1,25D3 on the crosstalk between MSC and macrophages and highlight the role of the hormone in bone regeneration.


2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Laura Saldaña ◽  
Gema Vallés ◽  
Fátima Bensiamar ◽  
Francisco José Mancebo ◽  
Eduardo García-Rey ◽  
...  

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Amin Salehpour ◽  
Mehdi Hedayati ◽  
Farzad Shidfar ◽  
Asal Neshatbini Tehrani ◽  
Ali Asghar Farshad ◽  
...  

Abstract Purpose 1,25-dihydroxyvitamin D3 may regulate adipogenesis in adipocytes in-vitro, but little is known about possible molecular mechanisms related to the inhibitory effect of 1,25-dihydroxyvitamin D3 on adipogenesis in humans҆ adipose tissue. Methodology In this study, human adipose-derived mesenchymal stem cells (hASCs) were cultured for 14 days in adipogenic differentiation media containing concentrations of 1,25-dihydroxyvitamin D3 (10−10–10−8 M). The extent of adipogenic differentiation in ASCs was assessed by Oil Red O staining and quantitative polymerase chain reaction (PCR) to determine expression levels of key adipogenic markers. Results Our results showed that vitamin D receptor (VDR), as a mediator of most actions of 1,25-dihydroxyvitamin D3, glucose trasporter-4 (GLUT4),and fatty acid binding protein-4 (FABP4) was expressed in vitamin D-treated hASCs. However, the protein level of these markers was lower than the control group. Treatment of human preadipocytes with 1,25-dihydroxyvitamin D3 significantly altered expression of adipogenic markers and triglyceride accumulation in a dose-dependent manner. 1,25-dihydroxyvitamin D3 at concentration of 10−8 M enhanced expression of sterol regulatory element-binding protein-1c (SREBP1c), CCAAT-enhancer-binding protein-β (C/EBPβ), a mitotic clonal expansion, peroxisome proliferator-activated receptor-gamma (PPARγ), fatty acid synthase (FASN), a marker of de novo lipogenesis,and lipoprotein lipase (LPL). Conclusion Our findings revealed that 1,25-dihydroxyvitamin D3 may provoke adipocyte development in critical periods of adipogenesis at concentration of 10−8 M, thereby leading to a greater risk of obesity in adulthood and an augmented risk of obesity-related diseases including diabetes, cardiovascular diseases, and some cancers.


Sign in / Sign up

Export Citation Format

Share Document