Nox4 expression in osteo-progenitors controls bone development in mice during early life.
Nox4 expression in osteo-progenitors controls bone development in mice during early life.
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DOI：
10.1038/s42003-022-03544-0
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发表时间：
2022-06-14
影响因子：
5.9
通讯作者：
中科院分区：
文献类型：
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受严格调控的细胞特异性NADPH氧化酶(NOx)是参与组织发育和干细胞自我更新的ROS信号分子的主要来源之一。我们已经确定了NOX4在出生后骨发育的骨祖细胞中的作用。在成骨细胞分化和骨发育的早期，骨组织中NOX4的表达和ROS的生成增加。NOX4基因敲除小鼠(NOX4-/-)和条件性基因敲除(CKO)小鼠肢体间充质中NOX4缺失的小鼠骨髓基质成骨细胞的自我更新、增殖和ROS产生均显著低于对照组(NOX4fl/fl)，但传代9代后又逆转。在性别上，3周龄CKO和NOX4-/-小鼠的骨体积、骨小梁数量和骨密度均显著低于Nox4fl/fl对照组。这反映在血清骨形成标志物碱性磷酸酶(ALP)和前胶原1完整N末端前肽(P1NP)的水平上。然而，在3周龄的CKO和NOX4-/-小鼠中，发育不良的骨形成在6周龄时迅速赶上对照组小鼠的水平，在13周龄时保持不同，而在32周龄的雄性小鼠中则相反。破骨细胞生成在各组间无差异，但反映破骨细胞活性的CTX1在3周龄的雄性CKO和NOX4-/-小鼠中显著高于对照组，而在32周龄的NOX4-/-小鼠中显著低于对照组。这些结果表明，骨和成骨细胞中NOX4的表达和ROS信号在成骨细胞的分化、增殖和成熟中起着重要的作用。在小鼠成骨细胞的分化、增殖和成熟过程中，NOX4的表达与活性氧信号通路密切相关。
Tightly regulated and cell-specific NADPH-oxidases (Nox) represent one of the major sources of reactive oxygen species (ROS) signaling molecules that are involved in tissue development and stem cell self-renewal. We have characterized the role of Nox4 in osteo-progenitors during postnatal bone development. Nox4 expression in bone and ROS generation were increased during early osteoblast differentiation and bone development. Stromal osteoblastic cell self-renewal, proliferation and ROS production were significantly lower in samples from whole-body Nox4 knockout mice (Nox4-/-) and conditional knockout (CKO) mice with depletion of Nox4 in the limb bud mesenchyme compared with those from control mice (Nox4fl/fl), but they were reversed after 9 passages. In both sexes, bone volume, trabecular number and bone mineral density were significantly lower in 3-week old CKO and Nox4-/- mice compared with Nox4fl/fl controls. This was reflected in serum levels of bone formation markers alkaline phosphatase (ALP) and procollagen 1 intact N-terminal propeptide (P1NP). However, under-developed bone formation in 3-week old CKO and Nox4-/- mice quickly caught up to levels of control mice by 6-week of age, remained no different at 13-week of age, and was reversed in 32-week old male mice. Osteoclastogenesis showed no differences among groups, however, CTX1 reflecting osteoclast activity was significantly higher in 3-week old male CKO and Nox4-/- mice compared with control mice, and significantly lower in 32-week old Nox4-/- mice compared with control mice. These data suggest that Nox4 expression and ROS signaling in bone and osteoblastic cells coordinately play an important role in osteoblast differentiation, proliferation and maturation. Nox4 expression combined with reactive oxygen species signaling are key to osteoblast differentiation, proliferation and maturation in mice.
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影响因子：
3.7
作者：
Arias, Clemente F.;Herrero, Miguel A.;Lopez, Jose M.
通讯作者：
Lopez, Jose M.
DOI：
10.1359/jbmr.081011
发表时间：
2009-02
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：
Chen JR;Lazarenko OP;Haley RL;Blackburn ML;Badger TM;Ronis MJ
通讯作者：
Ronis MJ
DOI：
10.1073/pnas.1012645108
发表时间：
2011-06-07
影响因子：
11.1
作者：
Lee, Kihyun;Won, Hee Yeon;Hwang, Eun Sook
通讯作者：
Hwang, Eun Sook
影响因子：
3.8
作者：
Chen, Jin-Ran;Lazarenko, Oxana P.;Ronis, Martin J. J.
通讯作者：
Ronis, Martin J. J.
影响因子：
4.8
作者：
Murray, Thomas V. A.;Smyrnias, Ioannis;Brewer, Alison C.
通讯作者：
Brewer, Alison C.