A novel link between chronic inflammation and humanin regulation in children
ObjectiveChildren with inflammatory bowel disease (IBD) often suffer from poor bone growth and impaired bone health. Humanin is a cytoprotective factor expressed in bone and other tissues and we hypothesized that humanin levels are suppressed in conditions of chronic inflammation. To address this, h...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1142310/full |
| _version_ | 1827376211037257728 |
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| author | Yunhan Zhao Outi Mäkitie Outi Mäkitie Saila Laakso Vera Fedosova Lars Sävendahl Farasat Zaman |
| author_facet | Yunhan Zhao Outi Mäkitie Outi Mäkitie Saila Laakso Vera Fedosova Lars Sävendahl Farasat Zaman |
| author_sort | Yunhan Zhao |
| collection | DOAJ |
| description | ObjectiveChildren with inflammatory bowel disease (IBD) often suffer from poor bone growth and impaired bone health. Humanin is a cytoprotective factor expressed in bone and other tissues and we hypothesized that humanin levels are suppressed in conditions of chronic inflammation. To address this, humanin levels were analyzed in serum samples from IBD patients and in ex vivo cultured human growth plate tissue specimens exposed to IBD serum or TNF alone.MethodsHumanin levels were measured by ELISA in serum from 40 children with IBD and 40 age-matched healthy controls. Growth plate specimens obtained from children undergoing epiphysiodesis surgery were cultured ex vivo for 48 hours while being exposed to IBD serum or TNF alone. The growth plate samples were then processed for immunohistochemistry staining for humanin, PCNA, SOX9 and TRAF2 expression. Dose-response effect of TNF was studied in the human chondrocytic cell line HCS-2/8. Ex vivo cultured fetal rat metatarsal bones were used to investigate the therapeutic effect of humanin.ResultsSerum humanin levels were significantly decreased in children with IBD compared to healthy controls. When human growth plate specimens were cultured with IBD serum, humanin expression was significantly suppressed in the growth plate cartilage. When cultured with TNF alone, the expression of humanin, PCNA, SOX9, and TRAF2 were all significantly decreased in the growth plate cartilage. Interestingly, treatment with the humanin analog HNG prevented TNF-induced bone growth impairment in cultured metatarsal bones.ConclusionOur data showing suppressed serum humanin levels in IBD children with poor bone health provides the first evidence for a potential link between chronic inflammation and humanin regulation. Such a link is further supported by the novel finding that serum from IBD patients suppressed humanin expression in ex vivo cultured human growth plates. |
| first_indexed | 2024-03-08T12:06:30Z |
| format | Article |
| id | doaj.art-3ff2b93082ee42e093977733db53d91f |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-03-08T12:06:30Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-3ff2b93082ee42e093977733db53d91f2024-01-23T06:10:06ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922024-01-011410.3389/fendo.2023.11423101142310A novel link between chronic inflammation and humanin regulation in childrenYunhan Zhao0Outi Mäkitie1Outi Mäkitie2Saila Laakso3Vera Fedosova4Lars Sävendahl5Farasat Zaman6Department of Women’s and Children’s Health, Karolinska Institutet and Pediatric Endocrinology Unit, Karolinska University Hospital, Solna, SwedenChildren’s Hospital, Helsinki University Hospital, University of Helsinki, Helsinki, FinlandDepartment of Molecular Medicine and Surgery, Karolinska Institutet, and Clinical Genetics, Karolinska University Hospital, Stockholm, SwedenChildren’s Hospital, Helsinki University Hospital, University of Helsinki, Helsinki, FinlandDepartment of Women’s and Children’s Health, Karolinska Institutet and Pediatric Endocrinology Unit, Karolinska University Hospital, Solna, SwedenDepartment of Women’s and Children’s Health, Karolinska Institutet and Pediatric Endocrinology Unit, Karolinska University Hospital, Solna, SwedenDepartment of Women’s and Children’s Health, Karolinska Institutet and Pediatric Endocrinology Unit, Karolinska University Hospital, Solna, SwedenObjectiveChildren with inflammatory bowel disease (IBD) often suffer from poor bone growth and impaired bone health. Humanin is a cytoprotective factor expressed in bone and other tissues and we hypothesized that humanin levels are suppressed in conditions of chronic inflammation. To address this, humanin levels were analyzed in serum samples from IBD patients and in ex vivo cultured human growth plate tissue specimens exposed to IBD serum or TNF alone.MethodsHumanin levels were measured by ELISA in serum from 40 children with IBD and 40 age-matched healthy controls. Growth plate specimens obtained from children undergoing epiphysiodesis surgery were cultured ex vivo for 48 hours while being exposed to IBD serum or TNF alone. The growth plate samples were then processed for immunohistochemistry staining for humanin, PCNA, SOX9 and TRAF2 expression. Dose-response effect of TNF was studied in the human chondrocytic cell line HCS-2/8. Ex vivo cultured fetal rat metatarsal bones were used to investigate the therapeutic effect of humanin.ResultsSerum humanin levels were significantly decreased in children with IBD compared to healthy controls. When human growth plate specimens were cultured with IBD serum, humanin expression was significantly suppressed in the growth plate cartilage. When cultured with TNF alone, the expression of humanin, PCNA, SOX9, and TRAF2 were all significantly decreased in the growth plate cartilage. Interestingly, treatment with the humanin analog HNG prevented TNF-induced bone growth impairment in cultured metatarsal bones.ConclusionOur data showing suppressed serum humanin levels in IBD children with poor bone health provides the first evidence for a potential link between chronic inflammation and humanin regulation. Such a link is further supported by the novel finding that serum from IBD patients suppressed humanin expression in ex vivo cultured human growth plates.https://www.frontiersin.org/articles/10.3389/fendo.2023.1142310/fullIBDTNFgrowth platehumaninchondrocyte |
| spellingShingle | Yunhan Zhao Outi Mäkitie Outi Mäkitie Saila Laakso Vera Fedosova Lars Sävendahl Farasat Zaman A novel link between chronic inflammation and humanin regulation in children Frontiers in Endocrinology IBD TNF growth plate humanin chondrocyte |
| title | A novel link between chronic inflammation and humanin regulation in children |
| title_full | A novel link between chronic inflammation and humanin regulation in children |
| title_fullStr | A novel link between chronic inflammation and humanin regulation in children |
| title_full_unstemmed | A novel link between chronic inflammation and humanin regulation in children |
| title_short | A novel link between chronic inflammation and humanin regulation in children |
| title_sort | novel link between chronic inflammation and humanin regulation in children |
| topic | IBD TNF growth plate humanin chondrocyte |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1142310/full |
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