Prenatal dexamethasone exposure (PDE) induces developmental toxicities of multi-organs and susceptibility to multi-diseases in offspring. However, the effects of PDE on osteoarthritis susceptibility in adult offspring and its mechanism have not been reported. In the present study, we treated pregnant Wistar rats with dexamethasone (0.2 mg/kg) daily on gestational days (GD) 9-20. Some pregnant rats were sacrificed on GD20, and the rest were delivered to obtain the postnatal offspring. The adult female offspring rats were performed with ovariectomy or sham operation during postnatal weeks 22-28. We found that PDE led to osteoarthritis phenotypes in articular cartilage and an increase in modified Mankin's score, but reduced the cartilage thickness in female adult offspring rats, which were more evident after ovariectomy. Moreover, PDE reduced the bone mass of subchondral bone in female adult offspring, which was aggravated by ovariectomy. The correlation analysis results indicated that the osteoarthritic phenotype and cartilage thickness were closely associated with the decreased bone mass of subchondral bone induced by PDE. Further, PDE retarded the development of primary and secondary ossification centers, then led to subchondral bone dysplasia, which could be partly mediated by the inhibited osteogenic function before and after birth. Collectively, the subchondral bone dysplasia partly participated in osteoarthritis susceptibility induced by PDE in female offspring rats.

中文翻译：

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软骨下骨发育不良部分参与地塞米松诱导的雌性后代大鼠骨关节炎易感性

产前地塞米松暴露 (PDE) 会导致后代多器官发育毒性和对多种疾病的易感性。然而，PDE对成年后代骨关节炎易感性的影响及其机制尚未见报道。在本研究中，我们在妊娠天数 (GD) 9-20 每天用地塞米松 (0.2 mg/kg) 治疗怀孕的 Wistar 大鼠。在GD20时处死一些怀孕的大鼠，其余的被分娩以获得产后后代。在产后22-28周期间对成年雌性后代大鼠进行卵巢切除术或假手术。我们发现 PDE 导致关节软骨中的骨关节炎表型和改良 Mankin 评分的增加，但降低了雌性成年后代大鼠的软骨厚度，这在卵巢切除后更为明显。而且，PDE降低了成年雌性后代软骨下骨的骨量，而卵巢切除术会加剧这种情况。相关性分析结果表明，骨关节炎表型和软骨厚度与PDE诱导的软骨下骨骨量减少密切相关。此外，PDE 延迟了初级和次级骨化中心的发育，然后导致软骨下骨发育不良，这可能部分是由出生前后成骨功能受抑制所介导的。总的来说，软骨下骨发育不良部分参与了雌性后代大鼠 PDE 诱导的骨关节炎易感性。相关性分析结果表明，骨关节炎表型和软骨厚度与PDE诱导的软骨下骨骨量减少密切相关。此外，PDE 延迟了初级和次级骨化中心的发育，然后导致软骨下骨发育不良，这可能部分是由出生前后成骨功能受抑制所介导的。总的来说，软骨下骨发育不良部分参与了雌性后代大鼠 PDE 诱导的骨关节炎易感性。相关性分析结果表明，骨关节炎表型和软骨厚度与PDE诱导的软骨下骨骨量减少密切相关。此外，PDE 延迟了初级和次级骨化中心的发育，然后导致软骨下骨发育不良，这可能部分是由出生前后成骨功能受抑制所介导的。总的来说，软骨下骨发育不良部分参与了雌性后代大鼠 PDE 诱导的骨关节炎易感性。