Overlapping functions of bone sialoprotein and pyrophosphate regulators in directing cementogenesis.
Overlapping functions of bone sialoprotein and pyrophosphate regulators in directing cementogenesis.
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DOI：
10.1016/j.bone.2017.08.027
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发表时间：
2017-12
期刊：
影响因子：
4.1
通讯作者：
Foster BL
中科院分区：
文献类型：
--
作者：
Ao M;Chavez MB;Chu EY;Hemstreet KC;Yin Y;Yadav MC;Millán JL;Fisher LW;Goldberg HA;Somerman MJ;Foster BL
尽管脱细胞牙骨质对于牙齿附着至关重要，但指导其发育和再生的因素仍知之甚少。无机焦磷酸盐 (PPi) 是一种矿化抑制剂，是牙骨质形成的关键调节剂：组织非特异性碱性磷酸酶 (Alpl/TNAP) 缺失小鼠（PPi 增加）的特点是牙骨质缺乏，而进行性强直蛋白 (Ank/ANK) 缺失小鼠（PPi 减少）的特点是牙骨质增加。骨唾液蛋白 (Bsp/BSP) 和骨桥蛋白 (Spp1/OPN) 是牙骨质的多功能细胞外基质成分，对细胞活动和矿化具有直接和间接影响。对 Bsp 敲除 (Bsp−/−) 小鼠牙槽发育的研究表明，脱细胞牙骨质严重减少，但潜在机制仍不清楚。 Bsp−/− 小鼠和 Alpl−/− 小鼠（后者具有升高的 PPi 和 OPN）之间牙骨质缺陷表型的相似性促使我们检查 BSP 是否通过调节 PPi 相关基因来发挥作用。 Bsp 的基因消融导致循环 PPi 增加 2 倍，改变 Alpl、Spp1 和 Ank 的 mRNA 表达，并增加牙周组织中的 OPN 蛋白。 Bsp 敲除 (KO) 成牙骨质细胞系的生成显示矿化能力显着降低，培养基中的 PPi 增加 50%，并且 Spp1 和 Ank mRNA 表达增加。虽然添加 2 μg/ml 重组 BSP 改变了成牙骨质细胞中的 Spp1、Ank 和 Enpp1 表达，但该剂量引起的变化并不依赖于整合素结合 RGD 基序或 Bsp−/− MAPK/ERK 信号通路上 Ank 的遗传消除。降低 PPi 小鼠背景可重建牙骨质形成，与 WT 相比，使脱细胞牙骨质体积增加 3 倍以上。然而，删除Ank并不能完全弥补BSP的缺失。与 Ank−/− 小鼠相比，Bsp−/−;Ank−/− 双缺陷小鼠的牙骨质厚度和体积平均减少 20-27%。从这些数据中，我们得出结论，PPi 代谢的扰动不仅仅驱动 Bsp−/− 小鼠的牙骨质病理学，而且 PPi 作为牙骨质调节剂比 BSP 更有效，如通过降低 PPi 来克服 BSP 损失的能力所示。我们建议 BSP 和 PPi 协同作用以指导牙骨质和可能的其他矿化组织的矿化。
Although acellular cementum is essential for tooth attachment, factors directing its development and regeneration remain poorly understood. Inorganic pyrophosphate (PPi), a mineralization inhibitor, is a key regulator of cementum formation: tissue-nonspecific alkaline phosphatase (Alpl/TNAP) null mice (increased PPi) feature deficient cementum, while progressive ankylosis protein (Ank/ANK) null mice (decreased PPi) feature increased cementum. Bone sialoprotein (Bsp/BSP) and osteopontin (Spp1/OPN) are multifunctional extracellular matrix components of cementum proposed to have direct and indirect effects on cell activities and mineralization. Studies on dentoalveolar development of Bsp knockout (Bsp−/−) mice revealed severely reduced acellular cementum, however underlying mechanisms remain unclear. The similarity in defective cementum phenotypes between Bsp−/− mice and Alpl−/− mice (the latter featuring elevated PPi and OPN), prompted us to examine whether BSP is operating by modulating PPi-associated genes. Genetic ablation of Bsp caused a 2-fold increase in circulating PPi, altered mRNA expression of Alpl, Spp1, and Ank, and increased OPN protein in the periodontia. Generation of a Bsp knock-out (KO) cementoblast cell line revealed significantly decreased mineralization capacity, 50% increased PPi in culture media, and increased Spp1 and Ank mRNA expression. While addition of 2 μg/ml recombinant BSP altered Spp1, Ank, and Enpp1 expression in cementoblasts, changes resulting from this dose were not dependent on the integrin-binding RGD motif or by genetic ablation of Ank on the Bsp−/− MAPK/ERK signaling pathway. Decreasing PPi mouse background reestablished cementum formation, allowing more than 3-fold increased acellular cementum volume compared to WT. However, deleting Ank did not fully compensate for the absence of BSP. Bsp−/−;Ank−/− double-deficient mice exhibited mean 20–27% reduced cementum thickness and volume compared to Ank−/− mice. From these data, we conclude that the perturbations in PPi metabolism are not solely driving the cementum pathology in Bsp−/− mice, and that PPi is more potent than BSP as a cementum regulator, as shown by the ability to override loss of BSP by lowering PPi. We propose that BSP and PPi work in concert to direct mineralization in cementum and likely other mineralized tissues.
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DOI：
10.1016/j.matbio.2016.02.003
发表时间：
2016-05
期刊：
Matrix biology : journal of the International Society for Matrix Biology
影响因子：
--
作者：
Chaudhary SC;Kuzynski M;Bottini M;Beniash E;Dokland T;Mobley CG;Yadav MC;Poliard A;Kellermann O;Millán JL;Napierala D
通讯作者：
Napierala D
影响因子：
4.3
作者：
Fong H;Chu EY;Tompkins KA;Foster BL;Sitara D;Lanske B;Somerman MJ
通讯作者：
Somerman MJ
DOI：
10.1016/0030-4220(62)90356-0
发表时间：
1962-01-01
期刊：
ORAL SURG ORAL MED AND ORAL PATHOL
影响因子：
--
作者：
BRUCKNER, R. J. N. H. RICKLES;PORTER, D. R.
通讯作者：
PORTER, D. R.
影响因子：
2.9
作者：
Fisher, LW;Fedarko, NS
通讯作者：
Fedarko, NS
影响因子：
4.1
作者：
Baht, Gurpreet S.;O'Young, Jason;Goldberg, Harvey A.
通讯作者：
Goldberg, Harvey A.