Diabetes Perturbs Bone Microarchitecture and Bone Strength through Regulation of Sema3A/IGF-1/β-Catenin in Rats
Purpose: Increasing evidence supported that semaphorin 3A (Sema3A), insulin-like growth factor (IGF)-1 and β-catenin were involved in the development of osteoporosis and diabetes. This study is aimed to evaluate whether Sema3A/IGF-1/β-catenin is directly involved in the alterations of bone microarch...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2017-01-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | http://www.karger.com/Article/FullText/455936 |
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| author | Rufeng Ma Lili Wang Baosheng Zhao Chenyue Liu Haixia Liu Ruyuan Zhu Beibei Chen Lin Li Dandan Zhao Fangfang Mo Yu Li Jianzhao Niu Guangjian Jiang Min Fu Dieter Bromme Sihua Gao Dongwei Zhang |
| author_facet | Rufeng Ma Lili Wang Baosheng Zhao Chenyue Liu Haixia Liu Ruyuan Zhu Beibei Chen Lin Li Dandan Zhao Fangfang Mo Yu Li Jianzhao Niu Guangjian Jiang Min Fu Dieter Bromme Sihua Gao Dongwei Zhang |
| author_sort | Rufeng Ma |
| collection | DOAJ |
| description | Purpose: Increasing evidence supported that semaphorin 3A (Sema3A), insulin-like growth factor (IGF)-1 and β-catenin were involved in the development of osteoporosis and diabetes. This study is aimed to evaluate whether Sema3A/IGF-1/β-catenin is directly involved in the alterations of bone microarchitecture and bone strength of diabetic rats. Methods: Diabetic rats were induced by streptozotocin and high fat diet exposure. Bone microarchitecture and strength in the femurs were evaluated by micro-CT scanning, three-point bending examination and the stainings of HE, alizarin red S and safranin O/fast green, respectively. The alterations of lumbar spines microarchitecture were also determined by micro-CT scanning. Western blot and immunohistochemical analyses were used to examine the expression of Sema3A, β-catenin, IGF-1, peroxisome proliferator-activated receptor γ (PPARγ) and cathepsin K in rat tibias. Results: Diabetic rats exhibited decreased trabecular numbers and bone formation, but an increased trabecular separation in the femurs and lumbar spines. Moreover, the increased bone fragility and decreased bone stiffness were evident in the femurs of diabetic rats. Diabetic rats also exhibited a pronounced bone phenotype which manifested by decreased expression of Sema3A, IGF-1 and β-catenin, as well as increased expression of cathepsin K and PPARγ. Conclusions: This study suggests that diabetes could perturb bone loss through the Sema3A/IGF-1/β-catenin pathway. Sema3A deficiency in bone may contribute to upregulation of PPARγ and cathepsin K expression, which further disrupts bone remodeling in diabetic rats. |
| first_indexed | 2024-12-11T13:01:12Z |
| format | Article |
| id | doaj.art-e41cb404dcd74697a71d70def5503ad8 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-11T13:01:12Z |
| publishDate | 2017-01-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-e41cb404dcd74697a71d70def5503ad82022-12-22T01:06:28ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782017-01-01411556610.1159/000455936455936Diabetes Perturbs Bone Microarchitecture and Bone Strength through Regulation of Sema3A/IGF-1/β-Catenin in RatsRufeng MaLili WangBaosheng ZhaoChenyue LiuHaixia LiuRuyuan ZhuBeibei ChenLin LiDandan ZhaoFangfang MoYu LiJianzhao NiuGuangjian JiangMin FuDieter BrommeSihua GaoDongwei ZhangPurpose: Increasing evidence supported that semaphorin 3A (Sema3A), insulin-like growth factor (IGF)-1 and β-catenin were involved in the development of osteoporosis and diabetes. This study is aimed to evaluate whether Sema3A/IGF-1/β-catenin is directly involved in the alterations of bone microarchitecture and bone strength of diabetic rats. Methods: Diabetic rats were induced by streptozotocin and high fat diet exposure. Bone microarchitecture and strength in the femurs were evaluated by micro-CT scanning, three-point bending examination and the stainings of HE, alizarin red S and safranin O/fast green, respectively. The alterations of lumbar spines microarchitecture were also determined by micro-CT scanning. Western blot and immunohistochemical analyses were used to examine the expression of Sema3A, β-catenin, IGF-1, peroxisome proliferator-activated receptor γ (PPARγ) and cathepsin K in rat tibias. Results: Diabetic rats exhibited decreased trabecular numbers and bone formation, but an increased trabecular separation in the femurs and lumbar spines. Moreover, the increased bone fragility and decreased bone stiffness were evident in the femurs of diabetic rats. Diabetic rats also exhibited a pronounced bone phenotype which manifested by decreased expression of Sema3A, IGF-1 and β-catenin, as well as increased expression of cathepsin K and PPARγ. Conclusions: This study suggests that diabetes could perturb bone loss through the Sema3A/IGF-1/β-catenin pathway. Sema3A deficiency in bone may contribute to upregulation of PPARγ and cathepsin K expression, which further disrupts bone remodeling in diabetic rats.http://www.karger.com/Article/FullText/455936Diabetic ratsSema3Aβ-cateninInsulin-like growth factor-1 (IGF)Peroxisome proliferator-activated receptor γ (PPAR γ)Cathepsin K |
| spellingShingle | Rufeng Ma Lili Wang Baosheng Zhao Chenyue Liu Haixia Liu Ruyuan Zhu Beibei Chen Lin Li Dandan Zhao Fangfang Mo Yu Li Jianzhao Niu Guangjian Jiang Min Fu Dieter Bromme Sihua Gao Dongwei Zhang Diabetes Perturbs Bone Microarchitecture and Bone Strength through Regulation of Sema3A/IGF-1/β-Catenin in Rats Cellular Physiology and Biochemistry Diabetic rats Sema3A β-catenin Insulin-like growth factor-1 (IGF) Peroxisome proliferator-activated receptor γ (PPAR γ) Cathepsin K |
| title | Diabetes Perturbs Bone Microarchitecture and Bone Strength through Regulation of Sema3A/IGF-1/β-Catenin in Rats |
| title_full | Diabetes Perturbs Bone Microarchitecture and Bone Strength through Regulation of Sema3A/IGF-1/β-Catenin in Rats |
| title_fullStr | Diabetes Perturbs Bone Microarchitecture and Bone Strength through Regulation of Sema3A/IGF-1/β-Catenin in Rats |
| title_full_unstemmed | Diabetes Perturbs Bone Microarchitecture and Bone Strength through Regulation of Sema3A/IGF-1/β-Catenin in Rats |
| title_short | Diabetes Perturbs Bone Microarchitecture and Bone Strength through Regulation of Sema3A/IGF-1/β-Catenin in Rats |
| title_sort | diabetes perturbs bone microarchitecture and bone strength through regulation of sema3a igf 1 β catenin in rats |
| topic | Diabetic rats Sema3A β-catenin Insulin-like growth factor-1 (IGF) Peroxisome proliferator-activated receptor γ (PPAR γ) Cathepsin K |
| url | http://www.karger.com/Article/FullText/455936 |
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