Department of Women's and Children´s Health, Karolinska Institutet and Pediatric Endocrinology Unit, Karolinska University Hospital, J9:30, Visionsgatan 4, 171 64, Solna, Sweden.
Biomedcode Hellas S.A., 34 Al. Fleming Str, 16672, Vari, Greece.
Sci Rep. 2022 Oct 28;12(1):18189. doi: 10.1038/s41598-022-22734-8.
Children with chronic inflammation are often treated with glucocorticoids (GCs) and many of them experience growth retardation. It is poorly understood how GCs interact with inflammatory cytokines causing growth failure as earlier experimental studies have been performed in healthy animals. To address this gap of knowledge, we used a transgenic mouse model where human TNF is overexpressed (huTNFTg) leading to chronic polyarthritis starting from the first week of age. Our results showed that femur bone length and growth plate height were significantly decreased in huTNFTg mice compared to wild type animals. In the growth plates of huTNFTg mice, increased apoptosis, suppressed Indian hedgehog, decreased hypertrophy, and disorganized chondrocyte columns were observed. Interestingly, the GC dexamethasone further impaired bone growth, accelerated chondrocyte apoptosis and reduced the number of chondrocyte columns in huTNFTg mice. We conclude that TNF and dexamethasone separately suppress chondrogenesis and bone growth when studied in an animal model of chronic inflammation. Our data give a possible mechanistic explanation to the commonly observed growth retardation in children with chronic inflammatory diseases treated with GCs.
患有慢性炎症的儿童通常接受糖皮质激素（GCs）治疗，其中许多人会出现生长迟缓。人们对 GC 如何与炎症细胞因子相互作用导致生长失败知之甚少，因为早期的实验研究是在健康动物中进行的。为了解决这一知识空白，我们使用了一种转基因小鼠模型，其中人 TNF 过表达（huTNFTg），导致从小鼠第一周开始出现慢性多关节炎。我们的研究结果表明，与野生型动物相比，huTNFTg 小鼠的股骨长度和生长板高度明显降低。在 huTNFTg 小鼠的生长板中，观察到细胞凋亡增加、印度刺猬因子抑制、肥大减少和软骨细胞柱排列紊乱。有趣的是，GC 地塞米松进一步损害了骨骼生长，加速了软骨细胞凋亡，并减少了 huTNFTg 小鼠的软骨细胞柱数量。我们得出结论，在慢性炎症动物模型中研究时，TNF 和地塞米松分别抑制软骨生成和骨骼生长。我们的数据为在接受 GCs 治疗的慢性炎症儿童中观察到的生长迟缓提供了一种可能的机制解释。
