Radiotherapy-induced bone deterioration is exacerbated in diabetic rats treated with streptozotocin
Following radiotherapy, patients have decreased bone mass and increased risk of fragility fractures. Diabetes mellitus (DM) is also reported to have detrimental effects on bone architecture and quality. However, no clinical or experimental study has systematically characterized the bone phenotype of...
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| Format: | Article |
| Language: | English |
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Associação Brasileira de Divulgação Científica
2021-10-01
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| Series: | Brazilian Journal of Medical and Biological Research |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2021001200610&tlng=en |
| _version_ | 1798019377558192128 |
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| author | Maogang Jiang Yuanjun Ding Shiwei Xu Xiaoxia Hao Yongqing Yang Erping Luo Da Jing Zedong Yan Jing Cai |
| author_facet | Maogang Jiang Yuanjun Ding Shiwei Xu Xiaoxia Hao Yongqing Yang Erping Luo Da Jing Zedong Yan Jing Cai |
| author_sort | Maogang Jiang |
| collection | DOAJ |
| description | Following radiotherapy, patients have decreased bone mass and increased risk of fragility fractures. Diabetes mellitus (DM) is also reported to have detrimental effects on bone architecture and quality. However, no clinical or experimental study has systematically characterized the bone phenotype of the diabetic patients following radiotherapy. After one month of streptozotocin injection, three-month-old male rats were subjected to focal radiotherapy (8 Gy, twice, at days 1 and 3), and then bone mass, microarchitecture, and turnover as well as bone cell activities were evaluated at 2 months post-irradiation. Micro-computed tomography results demonstrated that DM rats exhibited greater deterioration in trabecular bone mass and microarchitecture following irradiation compared with the damage to bone structure induced by DM or radiotherapy. The serum biochemical, bone histomorphometric, and gene expression assays revealed that DM combined with radiotherapy showed lower bone formation rate, osteoblast number on bone surface, and expression of osteoblast-related markers (ALP, Runx2, Osx, and Col-1) compared with DM or irradiation alone. DM plus irradiation also caused higher bone resorption rate, osteoclast number on bone surface, and expression of osteoclast-specific markers (TRAP, cathepsin K, and calcitonin receptor) than DM or irradiation treatment alone. Moreover, lower osteocyte survival and higher expression of Sost and DKK1 genes (two negative modulators of Wnt signaling) were observed in rats with combined DM and radiotherapy. Together, these findings revealed a higher deterioration of the diabetic skeleton following radiotherapy, and emphasized the clinical importance of health maintenance. |
| first_indexed | 2024-04-11T16:39:43Z |
| format | Article |
| id | doaj.art-c50c895140854600a34b92cd4f558eba |
| institution | Directory Open Access Journal |
| issn | 1414-431X |
| language | English |
| last_indexed | 2024-04-11T16:39:43Z |
| publishDate | 2021-10-01 |
| publisher | Associação Brasileira de Divulgação Científica |
| record_format | Article |
| series | Brazilian Journal of Medical and Biological Research |
| spelling | doaj.art-c50c895140854600a34b92cd4f558eba2022-12-22T04:13:42ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research1414-431X2021-10-01541210.1590/1414-431x2021e11550Radiotherapy-induced bone deterioration is exacerbated in diabetic rats treated with streptozotocinMaogang Jianghttps://orcid.org/0000-0001-8014-1337Yuanjun Dinghttps://orcid.org/0000-0002-6511-6405Shiwei Xuhttps://orcid.org/0000-0001-8519-063XXiaoxia Haohttps://orcid.org/0000-0002-5839-5469Yongqing Yanghttps://orcid.org/0000-0002-0372-4624Erping Luohttps://orcid.org/0000-0003-0275-4992Da Jinghttps://orcid.org/0000-0002-1603-549XZedong Yanhttps://orcid.org/0000-0002-2309-2978Jing Caihttps://orcid.org/0000-0001-9688-2957Following radiotherapy, patients have decreased bone mass and increased risk of fragility fractures. Diabetes mellitus (DM) is also reported to have detrimental effects on bone architecture and quality. However, no clinical or experimental study has systematically characterized the bone phenotype of the diabetic patients following radiotherapy. After one month of streptozotocin injection, three-month-old male rats were subjected to focal radiotherapy (8 Gy, twice, at days 1 and 3), and then bone mass, microarchitecture, and turnover as well as bone cell activities were evaluated at 2 months post-irradiation. Micro-computed tomography results demonstrated that DM rats exhibited greater deterioration in trabecular bone mass and microarchitecture following irradiation compared with the damage to bone structure induced by DM or radiotherapy. The serum biochemical, bone histomorphometric, and gene expression assays revealed that DM combined with radiotherapy showed lower bone formation rate, osteoblast number on bone surface, and expression of osteoblast-related markers (ALP, Runx2, Osx, and Col-1) compared with DM or irradiation alone. DM plus irradiation also caused higher bone resorption rate, osteoclast number on bone surface, and expression of osteoclast-specific markers (TRAP, cathepsin K, and calcitonin receptor) than DM or irradiation treatment alone. Moreover, lower osteocyte survival and higher expression of Sost and DKK1 genes (two negative modulators of Wnt signaling) were observed in rats with combined DM and radiotherapy. Together, these findings revealed a higher deterioration of the diabetic skeleton following radiotherapy, and emphasized the clinical importance of health maintenance.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2021001200610&tlng=enRadiotherapyDiabetes mellitus (DM)Bone lossOsteoblastsOsteocytes |
| spellingShingle | Maogang Jiang Yuanjun Ding Shiwei Xu Xiaoxia Hao Yongqing Yang Erping Luo Da Jing Zedong Yan Jing Cai Radiotherapy-induced bone deterioration is exacerbated in diabetic rats treated with streptozotocin Brazilian Journal of Medical and Biological Research Radiotherapy Diabetes mellitus (DM) Bone loss Osteoblasts Osteocytes |
| title | Radiotherapy-induced bone deterioration is exacerbated in diabetic rats treated with streptozotocin |
| title_full | Radiotherapy-induced bone deterioration is exacerbated in diabetic rats treated with streptozotocin |
| title_fullStr | Radiotherapy-induced bone deterioration is exacerbated in diabetic rats treated with streptozotocin |
| title_full_unstemmed | Radiotherapy-induced bone deterioration is exacerbated in diabetic rats treated with streptozotocin |
| title_short | Radiotherapy-induced bone deterioration is exacerbated in diabetic rats treated with streptozotocin |
| title_sort | radiotherapy induced bone deterioration is exacerbated in diabetic rats treated with streptozotocin |
| topic | Radiotherapy Diabetes mellitus (DM) Bone loss Osteoblasts Osteocytes |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2021001200610&tlng=en |
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