Biomedcode scientists have coauthored a paper published in Scientific Reports  that provides for the first time a possible mechanistic explanation to the growth retardation commonly observed in children with chronic inflammatory diseases treated with glucocorticoids. The Tg197 human TNF transgenic mice were used as a tool to show that TNF overexpression and dexamethasone treatment impair bone growth separately and in an additive manner.

Published in Scientific Reports 2022 Oct 28;12(1):18189. doi: 10.1038/s41598-022-22734-8

TNF overexpression and dexamethasone treatment impair chondrogenesis and bone growth in an additive manner

Yunhan Zhao, Bettina Celvin, Maria C. Denis, Niki Karagianni, Cecilia Aulin, Farasat Zaman & Lars Sävendahl


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.

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