TY  - JOUR
A1  - Chen, Jin-Ran
A1  - Lazarenko, Oxana P.
A1  - Blackburn, Michael L.
A1  - Chen, Jennifer F.
A1  - Randolph, Christopher E.
A1  - Zabaleta, Jovanny
A1  - Schröder, Katrin
A1  - Pedersen, Kim B.
A1  - Ronis, Martin
T1  - Nox4 expression in osteo-progenitors controls bone development in mice during early life
T2  - Communications biology
N2  - 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.
KW  - Research data
KW  - Self-renewal
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/63263
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-632636
SN  - 2399-3642
N1  - Additional data related to the paper are available from the corresponding author on reasonable request. RNA-Seq data were deposited in the Gene Expression Omnibus database as GEO submission number GSE195454.
N1  - This work was supported in part by National Institute of Health grant R37 AA18282 (M.J.J.R.) and supported by USDA-ARS Project 6026-51000-012-06S to Arkansas Children’s Nutrition Center sub-award to J.R.C.
VL  - 5
IS  - art. 583
SP  - 1
EP  - 12
PB  - Springer Nature
CY  - London
ER  -