TNF overexpression and dexamethasone treatment impair chondrogenesis and bone growth in an additive manner
Abstract 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....
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-10-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-22734-8 |
| _version_ | 1811256996454727680 |
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| author | Yunhan Zhao Bettina Celvin Maria C. Denis Niki Karagianni Cecilia Aulin Farasat Zaman Lars Sävendahl |
| author_facet | Yunhan Zhao Bettina Celvin Maria C. Denis Niki Karagianni Cecilia Aulin Farasat Zaman Lars Sävendahl |
| author_sort | Yunhan Zhao |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-12T17:50:37Z |
| format | Article |
| id | doaj.art-2402ec5452e543b08d1b549842f78486 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-12T17:50:37Z |
| publishDate | 2022-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-2402ec5452e543b08d1b549842f784862022-12-22T03:22:31ZengNature PortfolioScientific Reports2045-23222022-10-0112111210.1038/s41598-022-22734-8TNF overexpression and dexamethasone treatment impair chondrogenesis and bone growth in an additive mannerYunhan Zhao0Bettina Celvin1Maria C. Denis2Niki Karagianni3Cecilia Aulin4Farasat Zaman5Lars Sävendahl6Department of Women’s and Children´s Health, Karolinska Institutet and Pediatric Endocrinology Unit, Karolinska University HospitalDepartment of Women’s and Children´s Health, Karolinska Institutet and Pediatric Endocrinology Unit, Karolinska University HospitalBiomedcode Hellas S.A.Biomedcode Hellas S.A.Department of Medicine Solna, Karolinska Institutet and Division of Rheumatology, Karolinska University HospitalDepartment of Women’s and Children´s Health, Karolinska Institutet and Pediatric Endocrinology Unit, Karolinska University HospitalDepartment of Women’s and Children´s Health, Karolinska Institutet and Pediatric Endocrinology Unit, Karolinska University HospitalAbstract 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.https://doi.org/10.1038/s41598-022-22734-8 |
| spellingShingle | Yunhan Zhao Bettina Celvin Maria C. Denis Niki Karagianni Cecilia Aulin Farasat Zaman Lars Sävendahl TNF overexpression and dexamethasone treatment impair chondrogenesis and bone growth in an additive manner Scientific Reports |
| title | TNF overexpression and dexamethasone treatment impair chondrogenesis and bone growth in an additive manner |
| title_full | TNF overexpression and dexamethasone treatment impair chondrogenesis and bone growth in an additive manner |
| title_fullStr | TNF overexpression and dexamethasone treatment impair chondrogenesis and bone growth in an additive manner |
| title_full_unstemmed | TNF overexpression and dexamethasone treatment impair chondrogenesis and bone growth in an additive manner |
| title_short | TNF overexpression and dexamethasone treatment impair chondrogenesis and bone growth in an additive manner |
| title_sort | tnf overexpression and dexamethasone treatment impair chondrogenesis and bone growth in an additive manner |
| url | https://doi.org/10.1038/s41598-022-22734-8 |
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