open access

https://doi.org/10.14943/doctoral.k14539

https://hdl.handle.net/2115/96796

IL-6欠損マウスにおける骨リモデリング促進と骨基質石灰化抑制の組織学的解析

英語

RANKL

2021-03-25

Hokkaido University

24p

We examined the femora of 8-week-old male, IL-6 deficient (IL-6 -/- ) mice and their wild-type littermates by micro-CT analysis, immunohistochemistry, and real-time PCR to clarify the biological function of interleukin 6 (IL-6) in long bones. IL-6 -/- femora showed an increased bone volume/tissue volume (BV/TV) but a reduced bone mineral density (BMD). Compared with the wild-type littermates, the tissue-nonspecific alkaline phosphatase (TNALPase) positive area/TV ratio and the gene expressions of Runx2 and Osterix were elevated; in addition, in the IL-6 -/- mice, the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts and the expression of Rankl (but not Rank and Opg) were increased. A considerable amount of unmineralized areas of bone matrix was observed using von Kossa staining in IL-6 -/- femoral metaphyases but not in the wild-type counterparts. Thus, osteoblastic activities appeared to be facilitated by accelerated bone remodeling; however, bone mineralization seemed to be less active with abundant sclerostin-reactive osteocytes. Interestingly, in IL-6 -/- femora, the gene expressions of Cd206 were elevated, and many F4/80-positive macrophages/monocytes, as well as CD206 immunoreactive macrophages in the primary trabeculae, had migrated closer to the growth plate, where intense RANKL immunoreactivity was seen. Therefore, it is possible that, in an IL-6 deficient state, CD206-positive macrophages may differentiate into osteoclasts when in contact with RANKL-reactive osteoblastic cells. Taken together, these findings indicate that IL-6 deficiency causes accelerated bone remodeling and reduced bone mineralization induced by abundant sclerostin synthesis, indicating impaired bone remodeling and mineralization.

2021-03-25

甲第14539号

博士(歯学)

(主査) 教授 網塚 憲生, 教授 田村 正人, 教授 飯村 忠浩

歯学研究科（口腔医学専攻）

博士論文

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