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| SFRP5 Inhibites Osteogenic Differentiation of Human Umbilical Cord-derived Mesenchymal Stem Cells Induced by BMP9 |
Yan ZHENG,Huan YAO,Ke YANG( ) |
| Department of Pediatric Research Institute, Children’s Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child development and Critical Disorders,Chongqing Key Laboratory of Pediatrics, Chongqing Engineering Research Center of Stem Cell Therapy,Chongqing 400014, China |
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Abstract Objectives: To determine the role of SFRP5 in bone morphogenetic proteins 9 (BMP9)—mediated osteogenesis in human umbilical cord-derived mesenchymal stem cells(hUC-MSCs). Methods: The hUC-MSCs are divided into control group,BMP9 group,BMP9+SFRP5 group and SFRP5 group. Alkaline phosphatase (ALP) activity was carried out on 3, 5 and 7 days respectively; while ALP staining on 7 days. Aizarin red staining and oil red O staining were detected on 21 days. Different groups of cells were collected for subcutaneous injection in nude mice. After 4 weeks, the ectopic bone formation was analyzed by micro-CT scanning. The specimens were stained with H.E. staining, Masson staining, Alcian blue staining and oil red O staining. Osteogenesis differentiation related proteins expression of Runx2 and OPN were detected by Western blot. Results: Compared with control, the ALP activity and alizarin red staining were higher than BMP9 group; and BMP9+SFRP5 group was lower than that of BMP9 group. A small quantity of lipid droplets was detected in BMP9 group; and lipid droplets increased significantly in BMP9+SFRP5 group and SFRP5 group. Ectopic bone formation subcutaneously in nude mice was observed in BMP9 group and BMP9+SFRP5 group. The bone density of BMP9+SFRP5 group was lower than BMP9 group(P<0.05). The osteogenetic differentiation in BMP9 group was greater than that in BMP9+SFRP5 group by H.E. staining, Masson staining and Alcian blue staining, and more adipogenesis in BMP9+SFRP5 group by oil red O staining. SFRP5 inhibited the protein expression of Runx2 and OPN induced by BMP9. Conclusion: SFRP5 can inhibit the osteogenic differentiation of human umbilical cord mesenchymal stem cells induced by BMP9.
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Received: 19 January 2018
Published: 13 August 2018
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Corresponding Authors:
Ke YANG
E-mail: 361885986@qq.com
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| [1] |
Sadie-Van G H, Crowther N J, Hough F S, et al. The interrelationship between bone and fat: from cellular see-saw to endocrine reciprocity. Cell Mol Life Sci, 2013,70(13):2331-2349.
doi: 10.1007/s00018-012-1211-2
pmid: 23178849
|
|
|
| [2] |
Sheu Y, Cauley J A . The role of bone marrow and visceral fat on bone metabolism. Curr Osteoporos Rep, 2011,9(2):67-75.
doi: 10.1007/s11914-011-0051-6
pmid: 4188476
|
|
|
| [3] |
Thomas H A, Antonio S, Antonia G, et al. Adipocyte accumulation in the bone marrow during obesity and aging impairs stem cell-based hematopoietic and bone regeneration. Stem Cell, 2017,20(6):771-784.
|
|
|
| [4] |
Hu W, Li L, Yang M, et al. Circulating SFRP5 is a signature of obesity-related. J Clin Endocrinol Metab, 2013,98(1):290-298.
doi: 10.1210/jc.2012-2466
|
|
|
| [5] |
Chen H, He Y, Wu D, et al. Bone marrow SFRP5 level is negatively associated with bone formation markers. Osteoporos Int, 2017,28(4):1305-1311.
doi: 10.1007/s00198-016-3873-3
pmid: 27986984
|
|
|
| [6] |
Li T, Xia M, Gao Y, et al. Human umbilical cord mesenchymal stem cells: an overview of their potential in cell-based therapy. Expert Opin Biol Ther, 2015,15(9):1293-1306.
doi: 10.1517/14712598.2015.1051528
|
|
|
| [7] |
Kang Q, Sun M H, Cheng H, et al. Characterization of the distinct orthotopic bone-forming activity of 14 BMPs using recombinant adenovirus-mediated gene delivery. Gene Ther, 2004,11(17):1312-1320.
doi: 10.1038/sj.gt.3302298
|
|
|
| [8] |
李娅莎, 刘星, 毕杨, 等. BMP9诱导人脐带间充质干细胞体内外成骨分化的作用研究. 中国生物工程杂志, 2016,36(5):20-26.
doi: 10.13523/j.cb.20160503
|
|
|
| [8] |
Li Y S, Liu X, Bi Y, et al. Effect of BMP9 on osteogenic differentiation of human umbilical cord mesenchymal stem cells in vitro and in vivo. China Biotechnology, 2016,36(5):20-26.
doi: 10.13523/j.cb.20160503
|
|
|
| [9] |
Abdallah B M . Marrow adipocytes inhibit the differentiation of mesenchymal stem cells into osteoblasts via suppressing BMP-signaling. J Biomed Sci, 2017,24(1):11.
doi: 10.1186/s12929-017-0321-4
|
|
|
| [10] |
Robert A K, Larissa N, Jessica H, et al. Changes in gene expression foreshadow diet-induced obesity in genetically identical mice. PLoS Genet, 2006,2(5):e81.
doi: 10.1371/journal.pgen.0020081
pmid: 1464831
|
|
|
| [11] |
Taipalesnmaki H, Abdalla B M, Aidahrnash A, et al. Wnt signaling mediates the crosstalk between bone marrow derived pre-adipocytic and pre-osteoblastic cell populations. Exp Cell Res, 2011,317(6):745-756.
doi: 10.1016/j.yexcr.2010.12.015
|
|
|
| [12] |
Cruciat C M, Niehrs C . Secreted and transmembrane wnt inhibitors and activators. Cold Spring Harb Perspect Biol, 2013,5(3):a015081.
|
|
|
| [13] |
Miyazono K, Maeda S, Imamura T . BMP receptor signaling: transcriptional targets, regulation of signals, and signaling crosstalk. Cytokine Growth Factor Rev, 2005,16(3):251-263.
doi: 10.1016/j.cytogfr.2005.01.009
|
|
|
| [14] |
Long L, Ormiston M L, Yang X , et al. Selective enhancement of endothelial BMPR-II with BMP9 reverses pulmonary arterial hypertension. Nat Med, 2015,21(7) : 777-785.
doi: 10.1038/nm.3877
pmid: 4496295
|
|
|
| [15] |
Alfaro M P, Vincent A, Saraswati S , et al. SFRP2 suppression of bone morphogenic protein (BMP) and Wnt signaling mediates mesenchymal stem cell (MSC) self-renewal promoting engraftment and myocardial repair. J Biol Chem, 2010,285(46):35645-35653.
doi: 10.1074/jbc.M110.135335
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