Prominent bone loss mediated by RANKL and IL-17 produced by CD4+ T cells in TallyHo/JngJ mice.
Increasing evidence that decreased bone density and increased rates of bone fracture are associated with abnormal metabolic states such as hyperglycemia and insulin resistance indicates that diabetes is a risk factor for osteoporosis. In this study, we observed that TallyHo/JngJ (TH) mice, a polygen...
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2011
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oai:doaj.org-article:d57b7c7e782d4236abdc3a4df0b782cb2021-11-18T06:56:49ZProminent bone loss mediated by RANKL and IL-17 produced by CD4+ T cells in TallyHo/JngJ mice.1932-620310.1371/journal.pone.0018168https://doaj.org/article/d57b7c7e782d4236abdc3a4df0b782cb2011-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21464945/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Increasing evidence that decreased bone density and increased rates of bone fracture are associated with abnormal metabolic states such as hyperglycemia and insulin resistance indicates that diabetes is a risk factor for osteoporosis. In this study, we observed that TallyHo/JngJ (TH) mice, a polygenic model of type II diabetes, spontaneously developed bone deformities with osteoporotic features. Female and male TH mice significantly gained more body weight than control C57BL/6 mice upon aging. Interestingly, bone density was considerably decreased in male TH mice, which displayed hyperglycemia. The osteoblast-specific bone forming markers osteocalcin and osteoprotegerin were decreased in TH mice, whereas osteoclast-driven bone resorption markers such as IL-6 and RANKL were significantly elevated in the bone marrow and blood of TH mice. In addition, RANKL expression was prominently increased in CD4+ T cells of TH mice upon T cell receptor stimulation, which was in accordance with enhanced IL-17 production. IL-17 production in CD4+ T cells was directly promoted by treatment with leptin while IFN-γ production was not. Moreover, blockade of IFN-γ further increased RANKL expression and IL-17 production in TH-CD4+ T cells. In addition, the osteoporotic phenotype of TH mice was improved by treatment with alendronate. These results strongly indicate that increased leptin in TH mice may act in conjunction with IL-6 to preferentially stimulate IL-17 production in CD4+ T cells and induce RANKL-mediated osteoclastogenesis. Accordingly, we propose that TH mice could constitute a beneficial model for osteoporosis.Hee Yeon WonJin-Ah LeeZong Sik ParkJin Sook SongHee Yun KimSu-Min JangSung-Eun YooYoumi RheeEun Sook HwangMyung Ae BaePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 3, p e18168 (2011) |
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Medicine R Science Q Hee Yeon Won Jin-Ah Lee Zong Sik Park Jin Sook Song Hee Yun Kim Su-Min Jang Sung-Eun Yoo Youmi Rhee Eun Sook Hwang Myung Ae Bae Prominent bone loss mediated by RANKL and IL-17 produced by CD4+ T cells in TallyHo/JngJ mice. |
| description |
Increasing evidence that decreased bone density and increased rates of bone fracture are associated with abnormal metabolic states such as hyperglycemia and insulin resistance indicates that diabetes is a risk factor for osteoporosis. In this study, we observed that TallyHo/JngJ (TH) mice, a polygenic model of type II diabetes, spontaneously developed bone deformities with osteoporotic features. Female and male TH mice significantly gained more body weight than control C57BL/6 mice upon aging. Interestingly, bone density was considerably decreased in male TH mice, which displayed hyperglycemia. The osteoblast-specific bone forming markers osteocalcin and osteoprotegerin were decreased in TH mice, whereas osteoclast-driven bone resorption markers such as IL-6 and RANKL were significantly elevated in the bone marrow and blood of TH mice. In addition, RANKL expression was prominently increased in CD4+ T cells of TH mice upon T cell receptor stimulation, which was in accordance with enhanced IL-17 production. IL-17 production in CD4+ T cells was directly promoted by treatment with leptin while IFN-γ production was not. Moreover, blockade of IFN-γ further increased RANKL expression and IL-17 production in TH-CD4+ T cells. In addition, the osteoporotic phenotype of TH mice was improved by treatment with alendronate. These results strongly indicate that increased leptin in TH mice may act in conjunction with IL-6 to preferentially stimulate IL-17 production in CD4+ T cells and induce RANKL-mediated osteoclastogenesis. Accordingly, we propose that TH mice could constitute a beneficial model for osteoporosis. |
| format |
article |
| author |
Hee Yeon Won Jin-Ah Lee Zong Sik Park Jin Sook Song Hee Yun Kim Su-Min Jang Sung-Eun Yoo Youmi Rhee Eun Sook Hwang Myung Ae Bae |
| author_facet |
Hee Yeon Won Jin-Ah Lee Zong Sik Park Jin Sook Song Hee Yun Kim Su-Min Jang Sung-Eun Yoo Youmi Rhee Eun Sook Hwang Myung Ae Bae |
| author_sort |
Hee Yeon Won |
| title |
Prominent bone loss mediated by RANKL and IL-17 produced by CD4+ T cells in TallyHo/JngJ mice. |
| title_short |
Prominent bone loss mediated by RANKL and IL-17 produced by CD4+ T cells in TallyHo/JngJ mice. |
| title_full |
Prominent bone loss mediated by RANKL and IL-17 produced by CD4+ T cells in TallyHo/JngJ mice. |
| title_fullStr |
Prominent bone loss mediated by RANKL and IL-17 produced by CD4+ T cells in TallyHo/JngJ mice. |
| title_full_unstemmed |
Prominent bone loss mediated by RANKL and IL-17 produced by CD4+ T cells in TallyHo/JngJ mice. |
| title_sort |
prominent bone loss mediated by rankl and il-17 produced by cd4+ t cells in tallyho/jngj mice. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/d57b7c7e782d4236abdc3a4df0b782cb |
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