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

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. © 2014 cheng et al.; licensee biomed central ltd.