Cell-autonomous heparanase modulates self-renewal and migration in bone marrow-derived mesenchymal stem cells.
Cell-autonomous heparanase modulates self-renewal and migration in bone marrow-derived mesenchymal stem cells.
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DOI：
10.1186/1423-0127-21-21
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发表时间：
2014-03-13
影响因子：
11
通讯作者：
Liu IH
中科院分区：
文献类型：
--
作者：
Cheng CC;Lee YH;Lin SP;Huangfu WC;Liu IH
干细胞的命运受到干细胞生态位的高度调控，干细胞生态位由独特的微环境组成，包括邻近细胞、信号和细胞外基质。骨髓间充质干细胞（BM-MSC）是多能干细胞，可能适用于多种病理状况。然而，BM-MSC 维持的利基微环境尚未明确表征。越来越多的证据表明，硫酸乙酰肝素糖胺聚糖（HS-GAGs）调节BM-MSCs的自我更新和分化，而乙酰肝素酶（HPSE1）的过度表达导致骨髓组织学特征的改变。在这里，我们抑制 BM-MSC 中细胞自主 HPSE1 的酶活性，以阐明 HPSE1 在 BM-MSC 中的生理作用。分离的小鼠 BM-MSC 表达 HPSE1，其 mRNA 和蛋白质（包括潜在形式和酶活性 HPSE1）的存在表明了这一点。在体外成骨分化过程中，尽管Hpse1的表达水平有所波动，但酶抑制并不影响成骨分化，这可能是由于基质金属蛋白酶9（Mmp9）的表达水平增加所致。然而，当 HPSE1 被酶抑制时，细胞增殖和集落形成效率降低。 HPSE1 抑制增强了 SDF-1/CXCR4 信号轴，进而增强了 BM-MSC 的迁移/锚定行为。我们进一步证明，HPSE1 的抑制减少了组蛋白 H4 赖氨酸残基上乙酰化标记的积累，表明 HPSE1 还调节染色质重塑。我们的研究结果表明细胞自主 HPSE1 调节 BM-MSC 的克隆形成、增殖潜力和迁移，并表明 HS-GAG 可能有助于 BM-MSC 的生态位微环境。
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. 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. 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.
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影响因子：
4
作者：
Buczek-Thomas, Jo Ann;Hsia, Edward;Rich, Celeste B.;Foster, Judith A.;Nugent, Matthew A.
通讯作者：
Nugent, Matthew A.
影响因子：
11.8
作者：
Kreuger, J;Perez, L;Cohen, SM
通讯作者：
Cohen, SM
影响因子：
20.3
作者：
Corselli, Mirko;Chin, Chee Jia;Peault, Bruno
通讯作者：
Peault, Bruno
影响因子：
20.3
作者：
Ichii, Michiko;Frank, Mark Barton;Kincade, Paul W.
通讯作者：
Kincade, Paul W.
DOI：
10.1111/j.1365-2184.1970.tb00347.x
发表时间：
1970-01-01
期刊：
CELL AND TISSUE KINETICS
影响因子：
--
作者：
FRIEDENSTEIN, AJ;CHAILAKHJAN, RK;LALYKINA, KS
通讯作者：
LALYKINA, KS