Trabecular bone turnover and bone marrow cell development after immobilization

固定后小梁骨转换和骨髓细胞发育

• 批准号: 08671706
• 负责人: SAKAI Akinori
• 金额: $ 0.96万
• 依托单位: University of Occupational and Environmental Health
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671706/
• 关键词: Immobilization; Bone marrow; Osteoporosis; Parathyroid hormone; Osteblast; Osteoclast; mRNA; Mouse; フローサイトメトリー; RT-PCR; 骨萎縮; 骨代謝回転; 形態計測

During the three years from 1996 to 1998, we clarified trabecular bone turnover and bone marrow cell development after immobilization and the effects of parathyroid hormone (PTH) on immobilization-related bone loss.Methods : 1)6 week-old ddY male mice were subjected to eitherright sciatic neurectomy (Nx) or sham operation for left limbs (Sham). Histomorphometrical study was perfonned on the proximal metaphysis of tibia. 2) Bone marrow cell development was evaluated 3) FACSanalysis was done. Using RT-PCR procedure, mRNA expression of PTH/PTHrP was studied. 4) Either of 4 or4O mug/kgBW of PTH was administered subcutaneously 5 times a week.Results : 1) Trabecular bone volume significantly decreased 14days after immobilization. The number of osteoclasts transiently increased and bone formation increased after immobilization. 2) Adherent cellnumber transiently decreased andreturned to the same values of the Sham group 12 days after immobilization. The number of osteoclast-like cell formed from the bone marrow cells obtained from the Nx limbs increased under PTH addition. 3) There was no differences in the number of Mac-1positive cells between the Nx and Sham limbs. PTH/PTHrP mRNA was elevated in the bone marrow cells obtained from the Nx limbs on day 7.4)4)PTH administration prevented immobilization-related bone loss.These results demonstrated that immbilization caused transient decrease in bone formation and increase in the number of osteoclasts, leading to significant bone loss. The number of adherentmarrow cells increased and the terminal differentiation process of osteoclasts was promoted by PTH.PTH administration prevented immobilization-related bone loss. PTH/PTHrP signaling pathway was promoted in the bone marrow cells of the immobilized limbs.

方法：1）6周龄ddY雄性小鼠，行右侧坐骨神经切除术（Nx）和左侧假手术（Sham），观察制动后松质骨转换和骨髓细胞发育的变化及甲状旁腺激素（PTH）对制动相关性骨丢失的影响。对胫骨近端干骺端进行组织形态计量学研究。2)3）流式细胞仪分析。RT-PCR法检测PTH/PTHrP mRNA的表达。4)结果：1）制动后14天，松质骨体积显著减少，14天后，松质骨体积显著减少，14天后，松质骨体积显著减少，14天后，松质骨体积显著减少，14天后，松质骨体积显著减少。制动后破骨细胞数量短暂增加，骨形成增加。2)贴壁细胞数短暂减少，制动后12天恢复至Sham组水平。从Nx肢获得的骨髓细胞形成的破骨细胞样细胞的数量在PTH添加下增加。3)Nx组和Sham组的Mac-1阳性细胞数无差异。第7天从Nx肢体获得的骨髓细胞中PTH/PTHrP mRNA升高。4）PTH给药防止了制动相关的骨丢失。这些结果表明，制动引起骨形成的短暂减少和破骨细胞数量的增加，导致显著的骨丢失。PTH可增加骨髓细胞的粘附数量，促进破骨细胞的终末分化，预防制动相关的骨丢失。制动肢体骨髓细胞PTH/PTHrP信号通路增强。

项目成果

酒井昭典、ほか: "新しい骨作用薬(3)副甲状腺ホルモン(PTH)" 腎と骨代謝. 11・4. 153 (1998)

Akinori Sakai 等：“新型骨活性药物（3）甲状旁腺激素（PTH）”《肾脏和骨代谢》11/4（1998）。

Sakai A, et al.: "Bone marrow capacity for bone cells and trabecular bone turnover in immobilized tibia after aciatic neurectomy in mice." Bone. 18・5. 479-486 (1996)

Sakai A 等人：“小鼠无神经神经切除术后骨细胞的骨髓容量和小梁骨转换。” 479-486。

Sakai A, et al.: "Bone marrow cell development and trabecular bone dynamics after ovariectomy in ddy mice." Bone. 23-5. 443-451 (1998)

Sakai A 等人：“ddy 小鼠卵巢切除术后的骨髓细胞发育和骨小梁动力学。”

Sakai A, et al.: "Human parathyroid hormone(1-34)prevents immobilization-related bone loss by regulating bone marrow capacity for bone cells in mice." Transactions of the third combined meeting of orthopaedic research societies of U.S.A., Canada, Europa a

Sakai A 等人：“人甲状旁腺激素 (1-34) 通过调节小鼠骨细胞的骨髓容量来防止固定相关的骨质流失。”

沖本信和、ほか: "ヒト副甲状腺ホルモン(1-34)週一回間欠投与および休薬が卵巣摘除ラット皮質骨の力学強度に及ぼす影響とその組織学的機序" 日本骨代謝学会雑誌. 15・7. 177-181 (1998)

Nobukazu Okimoto 等：“每周间歇性施用和停用人甲状旁腺激素（1-34）对去势大鼠皮质骨机械强度的影响及其组织学机制”日本骨代谢学会杂志 15・7。 177-181（1998）