miR-29 suppression of osteonectin in osteoblasts: regulation during differentiation and by canonical Wnt signaling.
miR-29 suppression of osteonectin in osteoblasts: regulation during differentiation and by canonical Wnt signaling.
复制标题
DOI：
10.1002/jcb.22243
复制
发表时间：
2009-09-01
影响因子：
4
通讯作者：
Delany, Anne M.
中科院分区：
文献类型：
--
作者：
Kapinas, Kristina;Kessler, Catherine B.;Delany, Anne M.
骨粘连蛋白（osteonectin，BM-40）是骨组织中含量最丰富的非胶原性基质蛋白，是一种富含半胱氨酸的酸性分泌蛋白。基质细胞蛋白作为骨重建的调节剂在骨骼中发挥着重要作用。在骨骼中，骨粘连蛋白对于维持骨量和平衡骨形成和响应甲状旁腺激素（PTH）的再吸收至关重要。它促进成骨细胞分化和细胞存活。骨连接素在骨骼和其他组织中的表达调控机制仍知之甚少。我们发现小鼠骨连接素3′非翻译区（UTR）的近端区域包含一个高度保守的显性调控基序，该基序与microRNA（miRs）-29 a和-29 c相互作用。用miR-29 a抑制剂转染成骨细胞可增加骨连接蛋白水平，而转染miR-29 a前体RNA可降低骨连接蛋白水平。miR-29 a和-29c在体外成骨细胞分化过程中增加。这些miRNA的上调与骨连接蛋白在基质成熟和晚期分化的矿化阶段的减少相关。相反，骨粘连蛋白的转录水平在此过程中保持相对恒定，这意味着抑制翻译。用LiCl处理成骨细胞诱导miR-29 a和-29c表达并降低骨连接素合成。当细胞用Dickkopf-1（Dkk-1）处理时，miR-29 a和-29c表达被抑制。这些数据表明，在成骨细胞分化过程中增加的经典Wnt信号传导诱导miR-29的表达。骨连接素和miR-29在骨骼外组织中共表达，并且成骨细胞中调节骨连接素的转录后机制可能在其他细胞系统中是活跃的。
The matricellular protein osteonectin, secreted protein acidic and rich in cysteine (SPARC, BM-40), is the most abundant non-collagenous matrix protein in bone. Matricellular proteins play a fundamental role in the skeleton as regulators of bone remodeling. In the skeleton, osteonectin is essential for the maintenance of bone mass and for balancing bone formation and resorption in response to parathyroid hormone (PTH). It promotes osteoblast differentiation and cell survival. Mechanisms regulating the expression of osteonectin in the skeleton and in other tissues remain poorly understood. We found that the proximal region of the mouse osteonectin 3′ untranslated region (UTR) contains a well-conserved, dominant regulatory motif that interacts with microRNAs (miRs)-29a and -29c. Transfection of osteoblastic cells with miR-29a inhibitors increased osteonectin protein levels, whereas transfection of miR-29a precursor RNA decreased osteonectin. miR-29a and -29c were increased during osteoblastic differentiation in vitro. The up-regulation of these miRNAs correlated with decreased osteonectin protein during the matrix maturation and mineralization phases of late differentiation. In contrast, osteonectin transcript levels remained relatively constant during this process, implying repression of translation. Treatment of osteoblasts with LiCl induced miR-29a and -29c expression and decreased osteonectin synthesis. When cells were treated with Dickkopf-1 (Dkk-1), miR-29a and -29c expression was repressed. These data suggest that canonical Wnt signaling, which is increased during osteoblastic differentiation, induces expression of miR-29. Osteonectin and miR-29 are co-expressed in extra-skeletal tissues, and the post-transcriptional mechanisms regulating osteonectin in osteoblasts are likely to be active in other cell systems.
登录
查看更多内容
DOI：
10.1073/pnas.85.9.2919
发表时间：
1988-05-01
影响因子：
11.1
作者：
BOLANDER, ME;YOUNG, MF;TERMINE, JD
通讯作者：
TERMINE, JD
影响因子：
64.5
作者：
Lewis, BP;Shih, IH;Burge, CB
通讯作者：
Burge, CB
影响因子：
2.9
作者：
Chandrasekaran, Vasu;Ambati, Jayakrishna;Taylor, Ethan Will
通讯作者：
Taylor, Ethan Will
影响因子：
15.9
作者：
Bradshaw, AD;Sage, EH
通讯作者：
Sage, EH
影响因子：
15.9
作者：
Delany, AM;Amling, M;Canalis, E
通讯作者：
Canalis, E