The serum levels of activin A and bone morphogenetic protein-4 and -6 in patients with fibrodysplasia ossificans progressiva
Abstract Background Fibrodysplasia ossificans progressiva (FOP) is an ultrarare and disabling genetic disorder of connective tissue characterized by congenital malformation of the great toes, and progressive heterotopic ossification (HO) in soft connective tissues. A gain-of-function mutation of act...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13023-023-02708-3 |
| _version_ | 1797827356482600960 |
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| author | Zhengqin Ye Siyi Wang Chang Shan Qi Zhu Ying Xue Keqin Zhang |
| author_facet | Zhengqin Ye Siyi Wang Chang Shan Qi Zhu Ying Xue Keqin Zhang |
| author_sort | Zhengqin Ye |
| collection | DOAJ |
| description | Abstract Background Fibrodysplasia ossificans progressiva (FOP) is an ultrarare and disabling genetic disorder of connective tissue characterized by congenital malformation of the great toes, and progressive heterotopic ossification (HO) in soft connective tissues. A gain-of-function mutation of activin A receptor type I (ACVR1) enables ACVR1 to recognize activin A as an agonist with bone morphogenetic protein (BMP) signalling that leads to HO. Previous studies confirmed that activin A stimulates BMP signalling in vitro and drives HO in mouse models of FOP. However, the roles for BMP4 and BMP6 in FOP are supported only by correlative evidence in vitro. Thus, it remains unclear whether the circulating levels of activin A, BMP4 and BMP6 correlate with flare-ups in FOP patients. Hence, we investigated the protein levels of activin A, BMP4 and BMP6 in the serum of FOP patients. Results We recruited 16 untreated FOP patients and 16 age- and sex- matched healthy control subjects in this study. The 16 FOP patients were retrospectively divided into the flare-up group (n = 8) and remission group (n = 8) depending on whether they had flare-ups or worsening of any joint movement in the last 6 months. The serum activin A, BMP4 and BMP6 levels were detected by enzyme-linked immunosorbent assay. The serum activin A, BMP4 and BMP6 levels were slightly higher in FOP patients (median: 434.05 pg/mL, 459.48 pg/mL and 67.84 pg/mL) versus healthy control subjects (median: 364.14 pg/mL, 450.39 pg/mL and 55.36 pg/mL). However, there were no statistically significant differences between the two groups (p > 0.05 for all items), nor were there significant differences between the flare-up and remission groups of FOP (p > 0.05 for all items). Univariate and multivariate logistic regression analyses showed that age, sex, and serum activin A, BMP4 and BMP6 levels were not related to flare-up in FOP patients. Conclusions There were no significant differences in the serum levels of activin A, BMP4 and BMP6 in FOP patients compared with healthy control subjects. Serum activin A, BMP4 and BMP6 proteins might not be the stimulators for FOP flare-up, and may not be biomarkers for FOP diagnosis. |
| first_indexed | 2024-04-09T12:46:58Z |
| format | Article |
| id | doaj.art-1acb140aaffb4553b1b214552f42f364 |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-04-09T12:46:58Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-1acb140aaffb4553b1b214552f42f3642023-05-14T11:27:26ZengBMCOrphanet Journal of Rare Diseases1750-11722023-05-011811810.1186/s13023-023-02708-3The serum levels of activin A and bone morphogenetic protein-4 and -6 in patients with fibrodysplasia ossificans progressivaZhengqin Ye0Siyi Wang1Chang Shan2Qi Zhu3Ying Xue4Keqin Zhang5Department of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, Tongji UniversityMedical School of Nantong University, Affiliated Hospital of Nantong UniversityDepartment of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, Tongji UniversityDepartment of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, Tongji UniversityDepartment of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, Tongji UniversityDepartment of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, Tongji UniversityAbstract Background Fibrodysplasia ossificans progressiva (FOP) is an ultrarare and disabling genetic disorder of connective tissue characterized by congenital malformation of the great toes, and progressive heterotopic ossification (HO) in soft connective tissues. A gain-of-function mutation of activin A receptor type I (ACVR1) enables ACVR1 to recognize activin A as an agonist with bone morphogenetic protein (BMP) signalling that leads to HO. Previous studies confirmed that activin A stimulates BMP signalling in vitro and drives HO in mouse models of FOP. However, the roles for BMP4 and BMP6 in FOP are supported only by correlative evidence in vitro. Thus, it remains unclear whether the circulating levels of activin A, BMP4 and BMP6 correlate with flare-ups in FOP patients. Hence, we investigated the protein levels of activin A, BMP4 and BMP6 in the serum of FOP patients. Results We recruited 16 untreated FOP patients and 16 age- and sex- matched healthy control subjects in this study. The 16 FOP patients were retrospectively divided into the flare-up group (n = 8) and remission group (n = 8) depending on whether they had flare-ups or worsening of any joint movement in the last 6 months. The serum activin A, BMP4 and BMP6 levels were detected by enzyme-linked immunosorbent assay. The serum activin A, BMP4 and BMP6 levels were slightly higher in FOP patients (median: 434.05 pg/mL, 459.48 pg/mL and 67.84 pg/mL) versus healthy control subjects (median: 364.14 pg/mL, 450.39 pg/mL and 55.36 pg/mL). However, there were no statistically significant differences between the two groups (p > 0.05 for all items), nor were there significant differences between the flare-up and remission groups of FOP (p > 0.05 for all items). Univariate and multivariate logistic regression analyses showed that age, sex, and serum activin A, BMP4 and BMP6 levels were not related to flare-up in FOP patients. Conclusions There were no significant differences in the serum levels of activin A, BMP4 and BMP6 in FOP patients compared with healthy control subjects. Serum activin A, BMP4 and BMP6 proteins might not be the stimulators for FOP flare-up, and may not be biomarkers for FOP diagnosis.https://doi.org/10.1186/s13023-023-02708-3Fibrodysplasia ossificans progressiva (FOP)Activin ABone morphogenetic protein 4 (BMP4)Bone morphogenetic protein 6 (BMP6) |
| spellingShingle | Zhengqin Ye Siyi Wang Chang Shan Qi Zhu Ying Xue Keqin Zhang The serum levels of activin A and bone morphogenetic protein-4 and -6 in patients with fibrodysplasia ossificans progressiva Orphanet Journal of Rare Diseases Fibrodysplasia ossificans progressiva (FOP) Activin A Bone morphogenetic protein 4 (BMP4) Bone morphogenetic protein 6 (BMP6) |
| title | The serum levels of activin A and bone morphogenetic protein-4 and -6 in patients with fibrodysplasia ossificans progressiva |
| title_full | The serum levels of activin A and bone morphogenetic protein-4 and -6 in patients with fibrodysplasia ossificans progressiva |
| title_fullStr | The serum levels of activin A and bone morphogenetic protein-4 and -6 in patients with fibrodysplasia ossificans progressiva |
| title_full_unstemmed | The serum levels of activin A and bone morphogenetic protein-4 and -6 in patients with fibrodysplasia ossificans progressiva |
| title_short | The serum levels of activin A and bone morphogenetic protein-4 and -6 in patients with fibrodysplasia ossificans progressiva |
| title_sort | serum levels of activin a and bone morphogenetic protein 4 and 6 in patients with fibrodysplasia ossificans progressiva |
| topic | Fibrodysplasia ossificans progressiva (FOP) Activin A Bone morphogenetic protein 4 (BMP4) Bone morphogenetic protein 6 (BMP6) |
| url | https://doi.org/10.1186/s13023-023-02708-3 |
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