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

Journal of Biomedical Science

I-Hsuan Liu²  Wei-Chun HuangFu¹  Shau-Ping Lin⁴  Yen-Hua Lee³  Chun-Chun Cheng⁵ 

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

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

Others  :  820991
DOI  :  10.1186/1423-0127-21-21

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

【 摘 要 】

Background

Stem 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.

Results

Isolated 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.

Conclusions

Our 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】

   
2014 Cheng et al.; licensee BioMed Central Ltd.

【 图 表 】

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