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Xianrong Zhang
Southern Medical University Nanfang Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-0992-5013
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Background: Prenatal dexamethasone exposure (PDE) induces low birth weight and retardation of fetal bone development which are associated with lower peak bone mass in adult offspring. Here we evaluated whether and how PDE affects postnatal long bone growth in mice offspring.
Methods: Pregnant mice were injected subcutaneously with dexamethasone (1.2 mg/kg/day) every morning from gestational day (GD) 12-14. Femurs and tibias of 2-, 4-, 6-, and 12-week-old female offspring were harvested for histological, immunofluorescence, flow cytometric analysis, or microcomputed tomography (μCT) measurement.
Results: PDE leads to impaired bone remodeling as well as decreased bone mass in the long bone of female mice offspring. During postnatal bone growth, significant decrease of CD45-CD29+CD105+Sca-1+ bone marrow mesenchymal stem cells (BMSCs) and CD45-Nestin+ cells, loss of type H vessels as well as increment of cellular senescence were found in metaphysis of long bone in mice offspring after PDE. We further show that eliminating the excessive senescent cells with dasatinib (5 mg/kg/day) and quercetin (50 mg/kg/day) during GD 12-14 rescues the above toxic effect of PDE on the postnatal long bone growth in female mice offspring.
Conclusion: Cellular senescence mediates the toxic effect of PDE on postnatal long bone growth in mice offspring, and inhibition of cellular senescence may be proposed for treating the retardation of bone growth caused by PDE.
Keywords
Dexamethasone, bone development, bone mesenchymal stem cells, cellular senescence
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View the published article at Stem Cell Research & Therapy.
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Posted 16 Jun, 2020
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Editorial decision: Accept
On 06 Jun, 2020
Review #1 received
Received 20 May, 2020
Review #3 received
Received 20 May, 2020
Review #2 received
Received 20 May, 2020
Reviewer #3 agreed
On 15 May, 2020
Reviewer #2 agreed
On 13 May, 2020
Reviewers invited
Invitations sent on 12 May, 2020
Reviewer #1 agreed
On 12 May, 2020
Editor assigned
On 10 May, 2020
Submission checks complete
On 09 May, 2020
Editor invited
On 09 May, 2020
No comments provided
Editorial decision: Major Revision
On 02 Apr, 2020
Review #3 received
Received 31 Mar, 2020
Review #2 received
Received 29 Mar, 2020
Review #1 received
Received 25 Mar, 2020
Reviewers invited
Invitations sent on 17 Mar, 2020
Reviewer #1 agreed
On 17 Mar, 2020
Reviewer #2 agreed
On 17 Mar, 2020
Reviewer #3 agreed
On 17 Mar, 2020
Editor assigned
On 13 Mar, 2020
Editor invited
On 12 Mar, 2020
Submission checks complete
On 11 Mar, 2020
First submitted
On 10 Mar, 2020
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Subject Areas
Stem Cell & Developmental Cell Biology
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See the published version of this preprint at Stem Cell Research & Therapy.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Xianrong Zhang
Southern Medical University Nanfang Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-0992-5013
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Stem Cell Research & Therapy.
Version 2
Posted 16 Jun, 2020
No community comments so far
Editorial decision: Accept
On 06 Jun, 2020
Review #1 received
Received 20 May, 2020
Review #3 received
Received 20 May, 2020
Review #2 received
Received 20 May, 2020
Reviewer #3 agreed
On 15 May, 2020
Reviewer #2 agreed
On 13 May, 2020
Reviewers invited
Invitations sent on 12 May, 2020
Reviewer #1 agreed
On 12 May, 2020
Editor assigned
On 10 May, 2020
Submission checks complete
On 09 May, 2020
Editor invited
On 09 May, 2020
No comments provided
Editorial decision: Major Revision
On 02 Apr, 2020
Review #3 received
Received 31 Mar, 2020
Review #2 received
Received 29 Mar, 2020
Review #1 received
Received 25 Mar, 2020
Reviewers invited
Invitations sent on 17 Mar, 2020
Reviewer #1 agreed
On 17 Mar, 2020
Reviewer #2 agreed
On 17 Mar, 2020
Reviewer #3 agreed
On 17 Mar, 2020
Editor assigned
On 13 Mar, 2020
Editor invited
On 12 Mar, 2020
Submission checks complete
On 11 Mar, 2020
First submitted
On 10 Mar, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Stem Cell & Developmental Cell Biology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Stem Cell Research & Therapy.
Background: Prenatal dexamethasone exposure (PDE) induces low birth weight and retardation of fetal bone development which are associated with lower peak bone mass in adult offspring. Here we evaluated whether and how PDE affects postnatal long bone growth in mice offspring.
Methods: Pregnant mice were injected subcutaneously with dexamethasone (1.2 mg/kg/day) every morning from gestational day (GD) 12-14. Femurs and tibias of 2-, 4-, 6-, and 12-week-old female offspring were harvested for histological, immunofluorescence, flow cytometric analysis, or microcomputed tomography (μCT) measurement.
Results: PDE leads to impaired bone remodeling as well as decreased bone mass in the long bone of female mice offspring. During postnatal bone growth, significant decrease of CD45-CD29+CD105+Sca-1+ bone marrow mesenchymal stem cells (BMSCs) and CD45-Nestin+ cells, loss of type H vessels as well as increment of cellular senescence were found in metaphysis of long bone in mice offspring after PDE. We further show that eliminating the excessive senescent cells with dasatinib (5 mg/kg/day) and quercetin (50 mg/kg/day) during GD 12-14 rescues the above toxic effect of PDE on the postnatal long bone growth in female mice offspring.
Conclusion: Cellular senescence mediates the toxic effect of PDE on postnatal long bone growth in mice offspring, and inhibition of cellular senescence may be proposed for treating the retardation of bone growth caused by PDE.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
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