The value of the hedgehog signal in osteoblasts in fluoride-induced bone-tissue injury
Abstract Objective This study was designed to observe the expression of important hedgehog (Hh) signal factors in the bone tissue of rats with chronic fluorosis and cultured osteoblasts in order to investigate the role and significance of the Hh signal in fluoride-induced bone injury. Methods Health...
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| Format: | Article |
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BMC
2021-02-01
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| Series: | Journal of Orthopaedic Surgery and Research |
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| Online Access: | https://doi.org/10.1186/s13018-021-02287-8 |
| _version_ | 1817997284053352448 |
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| author | Chaonan Deng Lin Xu Ying Zhang Lina Zhao Yan Linghu Yanni Yu |
| author_facet | Chaonan Deng Lin Xu Ying Zhang Lina Zhao Yan Linghu Yanni Yu |
| author_sort | Chaonan Deng |
| collection | DOAJ |
| description | Abstract Objective This study was designed to observe the expression of important hedgehog (Hh) signal factors in the bone tissue of rats with chronic fluorosis and cultured osteoblasts in order to investigate the role and significance of the Hh signal in fluoride-induced bone injury. Methods Healthy Sprague-Dawley (SD) rats were randomly divided into four groups: the control group, the fluorosis group (F Group), the fluoride + blocker group (F + Cycl group: rats were treated with fluoride + cyclopamine), and the fluoride + blocker control group (F + DMSO group). After 6 months of intervention, the urinary fluoride content of rats in each group was detected. The primary osteoblasts of rats were selected for cell experiment, and the experiment was carried out after the cells were passaged from the second to the fourth generation. Results The proliferation rate of primary rat osteoblasts presented time-affected and dose-affected relationships in a short time under treatment with a low dose of sodium fluoride (NaF), but the proliferation of osteoblasts was inhibited by long-term and high-dose NaF exposure. In the F group, the alkaline phosphatase (ALP) activity of osteoblasts increased gradually. The ALP activity was lower in the F + Cycl group than in the F group, and there was no significant difference between the F + DMSO group and F group. With the increase in fluoride exposure, the expression of Hh signal factors and osteogenic-related factor proteins increased gradually. The expressions of Indian hedgehog (Ihh), smoothened (Smo), Glioma-associated oncogene homolog (Gli) 2, and Runt-related transcription factor 2 (Runx2)in the F + Cycl group increased with the dose of fluoride but they were significantly inhibited compared with the F group. Compared with the control group, the content of urinary fluoride in the F group was significantly higher (P < 0.05), but there was no significant change in urinary fluoride content in the F + Cycl group and the F + DMSO group. Compared with the control group, the serum bone alkaline phosphatase (BALP) contents of rats in the other groups increased after 6 months’ intake of fluoride water (P < 0.05). After drug blocking, the serum BALP content in the F + Cycl group was lower than that in the F + DMSO group (P < 0.05). The BALP content in the F + DMSO group was similar to that in the F group: it did not decrease. The mRNA expressions of Ihh, Smo, Gli2, and Runx2 in bone tissue of the F group were significantly higher than those in the control group (P < 0.05). After cyclopamine blocking, the expressions decreased (P < 0.05), but the differences between the F + DMSO group and F group were not statistically significant. Conclusion Hh signal plays an important role in fluoride-induced bone injury. The effective inhibition of cyclopamine is expected to be a new target for the treatment of skeletal damage caused by fluorosis. |
| first_indexed | 2024-04-14T02:35:58Z |
| format | Article |
| id | doaj.art-c9f4fb08169a4d399c82ed5a0223a759 |
| institution | Directory Open Access Journal |
| issn | 1749-799X |
| language | English |
| last_indexed | 2024-04-14T02:35:58Z |
| publishDate | 2021-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Orthopaedic Surgery and Research |
| spelling | doaj.art-c9f4fb08169a4d399c82ed5a0223a7592022-12-22T02:17:27ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2021-02-0116111010.1186/s13018-021-02287-8The value of the hedgehog signal in osteoblasts in fluoride-induced bone-tissue injuryChaonan Deng0Lin Xu1Ying Zhang2Lina Zhao3Yan Linghu4Yanni Yu5Department of Pathology, Affiliated Hospital of GuiZhou Medical UniversityDepartment of Pathology, Affiliated Hospital of GuiZhou Medical UniversityDepartment of Pathology, Affiliated Hospital of GuiZhou Medical UniversityDepartment of Pathology, Affiliated Hospital of GuiZhou Medical UniversityDepartment of Pathology, GuiZhou Medical UniversityDepartment of Pathology, Affiliated Hospital of GuiZhou Medical UniversityAbstract Objective This study was designed to observe the expression of important hedgehog (Hh) signal factors in the bone tissue of rats with chronic fluorosis and cultured osteoblasts in order to investigate the role and significance of the Hh signal in fluoride-induced bone injury. Methods Healthy Sprague-Dawley (SD) rats were randomly divided into four groups: the control group, the fluorosis group (F Group), the fluoride + blocker group (F + Cycl group: rats were treated with fluoride + cyclopamine), and the fluoride + blocker control group (F + DMSO group). After 6 months of intervention, the urinary fluoride content of rats in each group was detected. The primary osteoblasts of rats were selected for cell experiment, and the experiment was carried out after the cells were passaged from the second to the fourth generation. Results The proliferation rate of primary rat osteoblasts presented time-affected and dose-affected relationships in a short time under treatment with a low dose of sodium fluoride (NaF), but the proliferation of osteoblasts was inhibited by long-term and high-dose NaF exposure. In the F group, the alkaline phosphatase (ALP) activity of osteoblasts increased gradually. The ALP activity was lower in the F + Cycl group than in the F group, and there was no significant difference between the F + DMSO group and F group. With the increase in fluoride exposure, the expression of Hh signal factors and osteogenic-related factor proteins increased gradually. The expressions of Indian hedgehog (Ihh), smoothened (Smo), Glioma-associated oncogene homolog (Gli) 2, and Runt-related transcription factor 2 (Runx2)in the F + Cycl group increased with the dose of fluoride but they were significantly inhibited compared with the F group. Compared with the control group, the content of urinary fluoride in the F group was significantly higher (P < 0.05), but there was no significant change in urinary fluoride content in the F + Cycl group and the F + DMSO group. Compared with the control group, the serum bone alkaline phosphatase (BALP) contents of rats in the other groups increased after 6 months’ intake of fluoride water (P < 0.05). After drug blocking, the serum BALP content in the F + Cycl group was lower than that in the F + DMSO group (P < 0.05). The BALP content in the F + DMSO group was similar to that in the F group: it did not decrease. The mRNA expressions of Ihh, Smo, Gli2, and Runx2 in bone tissue of the F group were significantly higher than those in the control group (P < 0.05). After cyclopamine blocking, the expressions decreased (P < 0.05), but the differences between the F + DMSO group and F group were not statistically significant. Conclusion Hh signal plays an important role in fluoride-induced bone injury. The effective inhibition of cyclopamine is expected to be a new target for the treatment of skeletal damage caused by fluorosis.https://doi.org/10.1186/s13018-021-02287-8OsteoblastsHh signalFluorosisBone-tissue injurySkeletal fluorosis |
| spellingShingle | Chaonan Deng Lin Xu Ying Zhang Lina Zhao Yan Linghu Yanni Yu The value of the hedgehog signal in osteoblasts in fluoride-induced bone-tissue injury Journal of Orthopaedic Surgery and Research Osteoblasts Hh signal Fluorosis Bone-tissue injury Skeletal fluorosis |
| title | The value of the hedgehog signal in osteoblasts in fluoride-induced bone-tissue injury |
| title_full | The value of the hedgehog signal in osteoblasts in fluoride-induced bone-tissue injury |
| title_fullStr | The value of the hedgehog signal in osteoblasts in fluoride-induced bone-tissue injury |
| title_full_unstemmed | The value of the hedgehog signal in osteoblasts in fluoride-induced bone-tissue injury |
| title_short | The value of the hedgehog signal in osteoblasts in fluoride-induced bone-tissue injury |
| title_sort | value of the hedgehog signal in osteoblasts in fluoride induced bone tissue injury |
| topic | Osteoblasts Hh signal Fluorosis Bone-tissue injury Skeletal fluorosis |
| url | https://doi.org/10.1186/s13018-021-02287-8 |
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