Cell-autonomous heparanase modulates self-renewal and migration in bone marrow-derived mesenchymal stem cells

Journal of Biomedical Science

Research

Yen-Hua Lee¹  I-Hsuan Liu²  Chun-Chun Cheng³  Shau-Ping Lin⁴  Wei-Chun HuangFu⁵ 

[1] Department of Animal Science and Technology, National Taiwan University, 106, Taipei, Taiwan;Department of Animal Science and Technology, National Taiwan University, 106, Taipei, Taiwan;Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, 106, Taipei, Taiwan;Institute of Biotechnology, National Taiwan University, 106, Taipei, Taiwan;Institute of Biotechnology, National Taiwan University, 106, Taipei, Taiwan;Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, 106, Taipei, Taiwan;Agricultural Biotechnology Research Center, Academia Sinica, 128, Taipei, Taiwan;Center for Systems Biology, National Taiwan University, 106, Taipei, Taiwan;The Institute for Cancer Biology and Drug Discovery, Taipei Medical University, 110, Taipei, Taiwan;

关键词: Bone marrow-derived mesenchymal stem cells;    Heparan sulfate proteoglycans;    Heparanase;    Glycosaminoglycans;   

DOI  :  10.1186/1423-0127-21-21

 received in 2013-11-08, accepted in 2014-03-04,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundStem cell-fate is highly regulated by stem cell niche, which is composed of a distinct microenvironment, including neighboring cells, signals and extracellular matrix. Bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent stem cells and are potentially applicable in wide variety of pathological conditions. However, the niche microenvironment for BM-MSCs maintenance has not been clearly characterized. Accumulating evidence indicated that heparan sulfate glycosaminoglycans (HS-GAGs) modulate the self-renewal and differentiation of BM-MSCs, while overexpression of heparanase (HPSE1) resulted in the change of histological profile of bone marrow. Here, we inhibited the enzymatic activity of cell-autonomous HPSE1 in BM-MSCs to clarify the physiological role of HPSE1 in BM-MSCs.ResultsIsolated mouse BM-MSCs express HPSE1 as indicated by the existence of its mRNA and protein, which includes latent form and enzymatically active HPSE1. During in vitro osteo-differentiations, although the expression levels of Hpse1 fluctuated, enzymatic inhibition did not affect osteogenic differentiation, which might due to increased expression level of matrix metalloproteinase 9 (Mmp9). However, cell proliferation and colony formation efficiency were decreased when HPSE1 was enzymatically inhibited. HPSE1 inhibition potentiated SDF-1/CXCR4 signaling axis and in turn augmented the migratory/anchoring behavior of BM-MSCs. We further demonstrated that inhibition of HPSE1 decreased the accumulation of acetylation marks on histone H4 lysine residues suggesting that HPSE1 also modulates the chromatin remodeling.ConclusionsOur findings indicated cell-autonomous HPSE1 modulates clonogenicity, proliferative potential and migration of BM-MSCs and suggested the HS-GAGs may contribute to the niche microenvironment of BM-MSCs.

【 授权许可】

Unknown   
© Cheng et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.