open access

https://doi.org/10.14943/doctoral.k13866

https://hdl.handle.net/2115/94360

副甲状腺ホルモン投与マウスにおける骨基質石灰化関連酵素群・膜輸送体の免疫局在

Enzymes/membrane transporters for bone mineralization

英語

MEPE

2020-03-25

Hokkaido University

22p

The present study aimed to demonstrate the immunolocalization and/or gene expressions of the enzymes and membrane transporters involved in mineralization of bone after intermittent administration of parathyroid hormone (PTH). The study especially focused on TNALP, ENPP1, and PHOSPHO1, which are involved in matrix vesicle-mediated mineralization, as well as PHEX and the SIBLING family, which regulate mineralization deep inside bone. Six-week-old male mice were subcutaneously injected with 20 μ?g/kg/day of human PTH [1-34] two times per day (n = 6) or four times per day (n = 6) for 2 weeks. Additionally, control mice (n = 6) received vehicle. Consistent with an increase in the volume of the femoral trabeculae, the mineral appositional rate increased after PTH administration. The areas positive for PHOSPHO1, TNALP, and ENPP1 in the femoral metaphyses expanded, and the gene expressions assessed by real-time PCR were elevated in PTH-administered specimens when compared with the findings in control specimens. The immunoreactivity and/or gene expressions of PHEX and the SIBLING family (MEPE, osteopontin, and DMP1) significantly increased after PTH administration. For example, MEPE immunoreactivity was evident in some osteocytes in PTH-administered specimens, but was hardly observed in control specimens. In contrast, mRNA encoding cathepsin B was significantly reduced. Therefore, the bone matrix deep inside might be further mineralized by PHEX/SIBLING family after PTH administration. In summary, it is likely that PTH accelerate mineralization to maintain a balance with elevated matrix synthesis, presumably by mediating TNALP/ENPP1 cooperation and stimulating PHEX/SIBLING family expression.

2020-03-25

甲第13866号

博士(歯学)

(主査) 教授 網塚 憲生, 教授 飯村 忠浩, 教授 田村 正人

歯学研究科（口腔医学専攻）

博士論文

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