Pigment epithelium derived factor regulates human Sost/Sclerostin and other osteocyte gene expression via the receptor and induction of Erk/GSK-3beta/beta-catenin signaling.
Pigment epithelium derived factor regulates human Sost/Sclerostin and other osteocyte gene expression via the receptor and induction of Erk/GSK-3beta/beta-catenin signaling.
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DOI：
10.1016/j.bbadis.2018.07.034
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发表时间：
2018-10
期刊：
影响因子：
--
通讯作者：
Niyibizi C
中科院分区：
文献类型：
--
作者：
Li F;Cain JD;Tombran-Tink J;Niyibizi C
编码色素上皮衍生因子 (PEDF) 的 Serpinf1 基因突变会导致 VI 型成骨不全症，其特点是矿化缺陷。我们报道了 PEDF 在矿化成骨细胞培养物中抑制了 Sost/Sclerostin 和其他骨细胞相关基因的表达，并表明这可能是 PEDF 调节基质矿化机制的一部分 (Li et al. J Cellular Phys. 2014)。我们使用长期分化的矿化成骨细胞培养物 (LTD) 来定义 PEDF 调节骨细胞基因表达的机制。 LTD培养物是通过在成骨培养基中培养人成骨细胞4个月，然后分析骨细胞相关基因和编码蛋白质而建立的。 LTD细胞合成硬化蛋白、基质细胞外磷酸糖蛋白(MEPE)和牙本质基质蛋白(DMP-1)，并且PEDF处理后它们的合成减少。用 PEDF 处理培养物诱导 Erk 和糖原合酶激酶 3-β (GSK-3β) 磷酸化，以及非磷酸化 β-连环蛋白的积累。在 PEDF 存在的情况下，抑制 Erk 激活和中和色素上皮衍生受体 (PEDF-R) 抗体可抑制 GSK-3β 磷酸化和非磷酸化 β-连环蛋白的积累。 Topflash 测定表明，PEDF 激活荧光素酶报告基因活性，并且该活性可通过用 Erk 抑制剂或 PEDF-R 中和抗体处理来抑制。在 PEDF 存在的情况下，Dickkopf 相关蛋白 1 对细胞的处理效果极小，表明 GSK-3β 磷酸化和非磷酸化 β-连环蛋白的积累可能不涉及骨细胞中的 LRP5/6。综上所述，数据表明 PEDF 通过其受体调节骨细胞基因表达，并可能参与 Erk/GSK-3β/β-catenin 信号通路。
Mutations in Serpinf1 gene which encodes pigment epithelium derived factor (PEDF) lead to osteogenesis imperfecta type VI whose hallmark is defective mineralization. We reported that PEDF suppressed expression of Sost/Sclerostin and other osteocyte related genes in mineralizing osteoblast cultures and suggested that this could be part of the mechanisms by which PEDF regulates matrix mineralization (Li et al. J Cellular Phys. 2014). We have used a long-term differentiated mineralizing osteoblast culture (LTD) to define mechanisms by which PEDF regulates osteocyte gene expression. LTD cultures were established by culturing human osteoblasts in an osteogenic medium for 4 months followed by analysis of osteocytes related genes and encoded proteins. LTD cells synthesized Sclerostin, matrix extracellular phosphoglycoprotein (MEPE) and dentin matrix protein (DMP-1) and their synthesis was reduced by treatment with PEDF. Treatment of the cultures with PEDF induced phosphorylation of Erk and glycogen synthase kinase 3-beta (GSK-3β), and accumulation of nonphosphorylated β-catenin. Inhibition of Erk activation and neutralizing antibodies to the pigment epithelium derived receptor (PEDF-R) suppressed GSK-3β phosphorylation and accumulation of nonphosphorylated β-catenin in presence of PEDF. Topflash assays demonstrated that PEDF activated luciferase reporter activity and this activity was inhibited by treatment with Erk inhibitor or neutralizing antibodies to PEDF-R. Dickkopf-related protein 1 treatment of the cells in presence of PEDF had minimal effect suggesting that GSK-3β phosphorylation and accumulation of nonphosphorylayted β-catenin may not involve LRP5/6 in osteocytes. Taken together, the data demonstrate that PEDF regulates osteocyte gene expression through its receptor and possible involvement of Erk/GSK-3β/β-catenin signaling pathway.
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影响因子：
2.3
作者：
Bai, Yu-jing;Huang, Lv-zhen;Li, Xiao-xin
通讯作者：
Li, Xiao-xin
影响因子：
4.8
作者：
David, Valentin;Martin, Aline;Rowe, Peter S. N.
通讯作者：
Rowe, Peter S. N.
影响因子：
8
作者：
Desbois-Mouthon, C;Cadoret, A;Capeau, J
通讯作者：
Capeau, J
影响因子：
4.4
作者：
Apte, RS;Barreiro, RA;Ferguson, TA
通讯作者：
Ferguson, TA
通过PTH受体下游的不同机制对机械负荷和PTH的响应控制骨变性。
DOI：
10.1002/jbmr.3011
发表时间：
2017-03
期刊：
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
影响因子：
--
作者：
Delgado-Calle J;Tu X;Pacheco-Costa R;McAndrews K;Edwards R;Pellegrini GG;Kuhlenschmidt K;Olivos N;Robling A;Peacock M;Plotkin LI;Bellido T
通讯作者：
Bellido T