Course-, dose-, and stage-dependent toxic effects of prenatal dexamethasone exposure on long bone development in fetal mice

Chen, Ze; Zhao, Xiulan; Li, Yunzepeng; Zhang, Rui; Nie, Zaihui; Cheng, Xiaohuan; Zhang, Xianrong; Wang, Hui

doi:10.1016/j.taap.2018.05.005

Cited by 34 publications

(30 citation statements)

References 42 publications

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“…Our recent study found that PDE during gestational day 12-14 (GD12-14) retards bone development in fetal mice [6]. Here we show that young and adult female mice offspring by PDE have impaired bone formation and signi cant lower bone mass.…”

Section: Introductionmentioning

confidence: 51%

“…Our previous work demonstrated that continuous PDE during GD 9-20 retards long bone development in fetal rats and leads to low bone mass in adult rat offspring [7], and further delineated that PDE at dose higher than 0.8 mg/kg/day during GD 12-14 developed severe retardation of long bone development in fetal mice [6]. In the present study, the data clearly indicate that PDE at 1.2 mg/kg/day during GD 12-14 induces low bone mass in 12-week-old mice offspring.…”

Section: Discussionmentioning

confidence: 92%

“…3.1 Adult mice offspring from PDE has low bone mass in the long bone Our previous work has shown the adverse effect of PDE on the long bone development in fetal mice [6]. We then tested whether long bone development retardation during prenatal period results in bone mass de cit in adult offspring.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, clinical trial data show that lower birth weight is associated with lower peak bone mass in adult offspring [4,5]. Evidence from experimental animal models by our group and others demonstrate that prenatal dexamethasone exposure (PDE) impairs long bone development in fetal animals [6][7][8][9], reduces bone mass in adult offspring [7,10]. These data imply that developmental overexposure to glucocorticoid alters bone programming and results in less bone mass in offspring.…”

Section: Introductionmentioning

confidence: 88%

“…Pathogen-free mice were maintained under standard conditions in a 12h light and 12h dark cycle, at 25 ± 3°C, with a relative humidity of 40-60%, and with food and tap water available ad libitum. PDE during GD 12-14 was applied according to the procedure previously described [6]. Brie y, virgin C57BL/6 female mice at 10-12 weeks old were mate with male mice overnight.…”

Section: Animalsmentioning

confidence: 99%

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Cellular senescence mediates the detrimental effect of prenatal dexamethasone exposure on postnatal long bone growth in mice offspring

Chai

et al. 2020

Preprint

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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.

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Section: Introductionmentioning

confidence: 51%

Section: Discussionmentioning

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 88%

Section: Animalsmentioning

confidence: 99%

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Cellular senescence mediates the detrimental effect of prenatal dexamethasone exposure on postnatal long bone growth in mice offspring

Chai

et al. 2020

Preprint

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Osteochondritis dissecans shows a severe course and poor outcome in patients with juvenile idiopathic arthritis: a matched pair study of 22 cases

et al. 2018

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Juvenile osteochondritis dissecans (JOCD) and juvenile idiopathic arthritis (JIA) are both common diseases which may affect joints and bony structures in pediatric patients. In some cases, JOCD and JIA occur at the same time. In this study, the course of JOCD in patients with JIA was therefore evaluated to provide possible recommendations for further treatment opportunities and control examinations. From 06/2012 to 03/2018 55 children with JOCD with or without JIA were examined. Inclusion criteria were: (1) age ≤ 16 years, (2) diagnosis of a JOCD with or without JIA and (3) two routine MRI controls. The JOCD evaluation based on the classification according to Bruns and the measurement of the largest extent via MRI. 18 of these 55 children met our criteria: 11 JOCD findings of 7 patients with JIA (group A) were matched according to age and localization of JOCD to 11 patients without JIA (group B). Mean age of disease onset of JIA was 8.2 years (oligo JIA) and of JOCD 11.6 years. The mean time follow-up was 17.7 months. At all observation time points more JOCD findings (with stage III° and IV°, respectively) along with a significant deterioration was seen in group A compared to group B. The comparison of the last MRI control between group A and group B shows a significant smaller defect size (decrease of 54.5%, p = 0.028) in group B (97.9 ± 48.9 mm) as in group A (185.1 ± 102.9 mm). In comparison of first (169.7 ± 84.2 mm) and last MRI (97.9 ± 48.9 mm) a significant decrease in lesion size of JOCD in group B was seen (decrease of 58.4%, p = 0.048). Patients with JIA show a more progressive and severe course of JOCD. Therefore, we recommend (1) the early use of MRI in patients with JIA and persistent joint pain to detect potential JOCD and (2) in presence of JIA and JOCD regular MRI follow-up controls to identify deteriorating JOCD findings and prevent early joint destruction in pediatric patients.

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Course-, dose-, and stage-dependent toxic effects of prenatal dexamethasone exposure on long bone development in fetal mice

Cited by 34 publications

References 42 publications

Cellular senescence mediates the detrimental effect of prenatal dexamethasone exposure on postnatal long bone growth in mice offspring

Cellular senescence mediates the detrimental effect of prenatal dexamethasone exposure on postnatal long bone growth in mice offspring

Osteochondritis dissecans shows a severe course and poor outcome in patients with juvenile idiopathic arthritis: a matched pair study of 22 cases

Developmental toxicity and programming alterations of multiple organs in offspring induced by medication during pregnancy

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