Astrocytes from the contused spinal cord inhibit oligodendrocyte differentiation of adult oligodendrocyte precursor cells by increasing the expression of bone morphogenetic proteins.
Astrocytes from the contused spinal cord inhibit oligodendrocyte differentiation of adult oligodendrocyte precursor cells by increasing the expression of bone morphogenetic proteins.
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DOI：
10.1523/jneurosci.5524-09.2011
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发表时间：
2011-04-20
期刊：
影响因子：
--
通讯作者：
Cao QL
中科院分区：
文献类型：
--
作者：
Wang Y;Cheng X;He Q;Zheng Y;Kim DH;Whittemore SR;Cao QL
促进髓鞘再生是促进创伤性脊髓损伤（SCI）后功能恢复的重要治疗策略。神经干细胞或少突胶质细胞前体细胞 (OPC) 的移植已被用于增强 SCI 后的髓鞘再生。然而，受损脊髓中的微环境抑制少突胶质细胞 (OL) 向 NSC 或 OPC 的分化。确定抑制受损脊髓中 OL 分化的信号通路可能会产生新的治疗策略，以增强 SCI 后的髓鞘再生和功能恢复。在本研究中，我们发现来自受损大鼠脊髓或其条件培养基的反应性星形胶质细胞抑制成年 OPC 的 OL 分化，同时促进星形胶质细胞分化。反应性星形胶质细胞及其条件培养基中骨形态发生蛋白（BMP）的表达显着增加。重要的是，通过 BMP 受体拮抗剂 noggin 阻断 BMP 活性，可通过增加 OL 与 OPC 的分化同时减少星形胶质细胞的生成，从而逆转活性星形胶质细胞对 OPC 分化的影响。这些数据表明，反应性星形胶质细胞中上调的骨形态发生蛋白是抑制OPCs OL分化并促进其星形胶质细胞分化的主要因素。这些数据表明，操纵内源性或移植的 NSC 或 OPC 中的 BMP 信号传导可能是一种有用的治疗策略，可增加其 OL 分化和髓鞘再生，并增强 SCI 后的功能恢复。
Promotion of remyelination is an important therapeutic strategy to facilitate functional recovery after traumatic spinal cord injury (SCI). Transplantation of neural stem cells or oligodendrocyte precursor cells (OPCs) has been used to enhance remyelination after SCI. However, the microenvironment in the injured spinal cord is inhibitory for oligodendrocyte (OL) differentiation of NSCs or OPCs. Identifying the signaling pathways that inhibit OL differentiation in the injured spinal cord could lead to new therapeutic strategies to enhance remyelination and functional recovery after SCI. In the present study, we show that reactive astrocytes from the injured rat spinal cord or their conditioned media inhibit OL differentiation of adult OPCs with concurrent promotion of astrocyte differentiation. The expression of bone morphogenetic proteins (BMP) is dramatically increased in the reactive astrocytes and their conditioned media. Importantly, blocking BMP activity by BMP receptor antagonist, noggin, reverse the effects of active astrocytes on OPC differentiation by increasing the differentiation of OL from OPCs while decreasing the generation of astrocytes. These data indicate that the upregulated bone morphogenetic proteins in the reactive astrocytes are major factors to inhibit OL differentiation of OPCs and to promote its astrocyte differentiation. These data suggest that manipulation of BMP signaling in the endogenous or grafted NSCs or OPCs may be a useful therapeutic strategy to increase their OL differentiation and remyelination and enhance functional recovery after SCI.