open access

https://doi.org/10.14943/doctoral.k16442

https://hdl.handle.net/2115/94870

Ⅱ型糖尿病モデルSpontaneously Diabetic Torii-Leprfa (SDT-fa/fa)ラット大腿骨の組織化学的解析

英語

histochemistry

2025-03-25

Hokkaido University

To elucidate the mechanisms underlying diabetic osteoporosis, we conducted a comprehensive histological examination of the femora in Spontaneously Diabetic Torii-Leprfa (SDT-fa/fa) rats, an established model for obesity-related type 2 diabetes. Femora from 12 30-week-old male SDT-fa/fa rats and age-matched Sprague–Dawley (SD) rats (controls) were used for detailed histochemical analyses, including TRAP, cathepsin K, ALP, PHOSPHO1, DMP-1, MEPE, sclerostin, and osteocalcin staining, as well as silver impregnation, von Kossa staining, and micro-CT imaging. Micro-CT and hematoxylin-eosin staining demonstrated significantly reduced trabecular bone volumes in the femoral metaphyses of SDT-fa/fa rats. While the number of TRAP-positive osteoclasts per bone surface (/BS) remained comparable between the two groups, SDT-fa/fa rats exhibited reduced areas of ALP-positive osteoblasts/BS and PHOSPHO1-reactive mature osteoblasts/BS. Silver impregnation revealed a well-organized osteocytic lacunar–canalicular system in both groups; however, immunostaining identified aberrant DMP-1 and MEPE expression localized predominantly in lacunae in SDT-fa/fa rats, whereas in SD rats, these peptides were evident in both lacunae and canaliculi. Additionally, intense osteocalcin and sclerostin immunoreactivity was detected in osteocytes, along with a higher proportion of osteocalcin-positive osteocytes, in SDT-fa/fa rats, distinguishing them from SD controls. In conclusion, SDT-fa/fa rats display a notable decline in osteoblastic function and distinctive distribution patterns of osteocyte-derived peptides, suggesting that this diabetic model may manifest alterations in osteoblastic activity and the osteocytic lacunar-canalicular network.

2025-03-25

甲第16442号

博士(歯学)

(主査) 教授 網塚 憲生, 教授 坂口 究, 教授 飯村 忠浩, 教授 樋田 京子, 准教授 長谷川 智香

歯学院（口腔医学専攻）

博士論文

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