Promotion effect of FGF23 on osteopenia in congenital scoliosis through FGFr3/TNAP/OPN pathway
Abstract. Background:. Congenital scoliosis (CS) is a complex spinal malformation of unknown etiology with abnormal bone metabolism. Fibroblast growth factor 23 (FGF23), secreted by osteoblasts and osteocytes, can inhibit bone formation and mineralization. This research aims to investigate the rela...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer
2023-06-01
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| Series: | Chinese Medical Journal |
| Online Access: | http://journals.lww.com/10.1097/CM9.0000000000002690 |
| _version_ | 1797791965078618112 |
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| author | Hongqi Zhang Gang Xiang Jiong Li Sihan He Yunjia Wang Ang Deng Yuxiang Wang Chaofeng Guo Xiuyuan Hao |
| author_facet | Hongqi Zhang Gang Xiang Jiong Li Sihan He Yunjia Wang Ang Deng Yuxiang Wang Chaofeng Guo Xiuyuan Hao |
| author_sort | Hongqi Zhang |
| collection | DOAJ |
| description | Abstract.
Background:. Congenital scoliosis (CS) is a complex spinal malformation of unknown etiology with abnormal bone metabolism. Fibroblast growth factor 23 (FGF23), secreted by osteoblasts and osteocytes, can inhibit bone formation and mineralization. This research aims to investigate the relationship between CS and FGF23.
Methods:. We collected peripheral blood from two pairs of identical twins for methylation sequencing of the target region. FGF23 mRNA levels in the peripheral blood of CS patients and age-matched controls were measured. Receiver operator characteristic (ROC) curve analyses were conducted to evaluate the specificity and sensitivity of FGF23. The expression levels of FGF23 and its downstream factors fibroblast growth factor receptor 3 (FGFr3)/tissue non-specific alkaline phosphatase (TNAP)/osteopontin (OPN) in primary osteoblasts from CS patients (CS-Ob) and controls (CT-Ob) were detected. In addition, the osteogenic abilities of FGF23-knockdown or FGF23-overexpressing Ob were examined.
Results:. DNA methylation of the FGF23 gene in CS patients was decreased compared to that of their identical twins, accompanied by increased mRNA levels. CS patients had increased peripheral blood FGF23 mRNA levels and decreased computed tomography (CT) values compared with controls. The FGF23 mRNA levels were negatively correlated with the CT value of the spine, and ROCs of FGF23 mRNA levels showed high sensitivity and specificity for CS. Additionally, significantly increased levels of FGF23, FGFr3, OPN, impaired osteogenic mineralization and lower TNAP levels were observed in CS-Ob. Moreover, FGF23 overexpression in CT-Ob increased FGFr3 and OPN levels and decreased TNAP levels, while FGF23 knockdown induced downregulation of FGFr3 and OPN but upregulation of TNAP in CS-Ob. Mineralization of CS-Ob was rescued after FGF23 knockdown.
Conclusions:. Our results suggested increased peripheral blood FGF23 levels, decreased bone mineral density in CS patients, and a good predictive ability of CS by peripheral blood FGF23 levels. FGF23 may contribute to osteopenia in CS patients through FGFr3/TNAP/OPN pathway. |
| first_indexed | 2024-03-13T02:26:18Z |
| format | Article |
| id | doaj.art-a9d850b9fea64cbe8c3b414131876f08 |
| institution | Directory Open Access Journal |
| issn | 0366-6999 2542-5641 |
| language | English |
| last_indexed | 2024-03-13T02:26:18Z |
| publishDate | 2023-06-01 |
| publisher | Wolters Kluwer |
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| series | Chinese Medical Journal |
| spelling | doaj.art-a9d850b9fea64cbe8c3b414131876f082023-06-30T01:54:37ZengWolters KluwerChinese Medical Journal0366-69992542-56412023-06-01136121468147710.1097/CM9.0000000000002690202306200-00011Promotion effect of FGF23 on osteopenia in congenital scoliosis through FGFr3/TNAP/OPN pathwayHongqi Zhang0Gang Xiang1Jiong Li2Sihan He3Yunjia Wang4Ang Deng5Yuxiang Wang6Chaofeng Guo7Xiuyuan Hao1Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan 410000, China1Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan 410000, China1Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan 410000, China1Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan 410000, China1Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan 410000, China1Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan 410000, China1Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan 410000, China1Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan 410000, ChinaAbstract. Background:. Congenital scoliosis (CS) is a complex spinal malformation of unknown etiology with abnormal bone metabolism. Fibroblast growth factor 23 (FGF23), secreted by osteoblasts and osteocytes, can inhibit bone formation and mineralization. This research aims to investigate the relationship between CS and FGF23. Methods:. We collected peripheral blood from two pairs of identical twins for methylation sequencing of the target region. FGF23 mRNA levels in the peripheral blood of CS patients and age-matched controls were measured. Receiver operator characteristic (ROC) curve analyses were conducted to evaluate the specificity and sensitivity of FGF23. The expression levels of FGF23 and its downstream factors fibroblast growth factor receptor 3 (FGFr3)/tissue non-specific alkaline phosphatase (TNAP)/osteopontin (OPN) in primary osteoblasts from CS patients (CS-Ob) and controls (CT-Ob) were detected. In addition, the osteogenic abilities of FGF23-knockdown or FGF23-overexpressing Ob were examined. Results:. DNA methylation of the FGF23 gene in CS patients was decreased compared to that of their identical twins, accompanied by increased mRNA levels. CS patients had increased peripheral blood FGF23 mRNA levels and decreased computed tomography (CT) values compared with controls. The FGF23 mRNA levels were negatively correlated with the CT value of the spine, and ROCs of FGF23 mRNA levels showed high sensitivity and specificity for CS. Additionally, significantly increased levels of FGF23, FGFr3, OPN, impaired osteogenic mineralization and lower TNAP levels were observed in CS-Ob. Moreover, FGF23 overexpression in CT-Ob increased FGFr3 and OPN levels and decreased TNAP levels, while FGF23 knockdown induced downregulation of FGFr3 and OPN but upregulation of TNAP in CS-Ob. Mineralization of CS-Ob was rescued after FGF23 knockdown. Conclusions:. Our results suggested increased peripheral blood FGF23 levels, decreased bone mineral density in CS patients, and a good predictive ability of CS by peripheral blood FGF23 levels. FGF23 may contribute to osteopenia in CS patients through FGFr3/TNAP/OPN pathway.http://journals.lww.com/10.1097/CM9.0000000000002690 |
| spellingShingle | Hongqi Zhang Gang Xiang Jiong Li Sihan He Yunjia Wang Ang Deng Yuxiang Wang Chaofeng Guo Xiuyuan Hao Promotion effect of FGF23 on osteopenia in congenital scoliosis through FGFr3/TNAP/OPN pathway Chinese Medical Journal |
| title | Promotion effect of FGF23 on osteopenia in congenital scoliosis through FGFr3/TNAP/OPN pathway |
| title_full | Promotion effect of FGF23 on osteopenia in congenital scoliosis through FGFr3/TNAP/OPN pathway |
| title_fullStr | Promotion effect of FGF23 on osteopenia in congenital scoliosis through FGFr3/TNAP/OPN pathway |
| title_full_unstemmed | Promotion effect of FGF23 on osteopenia in congenital scoliosis through FGFr3/TNAP/OPN pathway |
| title_short | Promotion effect of FGF23 on osteopenia in congenital scoliosis through FGFr3/TNAP/OPN pathway |
| title_sort | promotion effect of fgf23 on osteopenia in congenital scoliosis through fgfr3 tnap opn pathway |
| url | http://journals.lww.com/10.1097/CM9.0000000000002690 |
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