Bone Marrow Cell Development and Signal Transduction in Bone Loss due to Skeletal Unloading.

骨髓细胞发育和骨骼卸载引起的骨丢失中的信号转导。

• 批准号: 14370475
• 负责人: SAKAI Akinori
• 金额: $ 2.62万
• 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 (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370475/
• 关键词: unloading; immobilization; trabecular bone; parathyroid hormone; osteblast; osteoclast; p53; c-fos; 荷重; CD31; CFU-f; アルカリフォスファターゼ; 骨髄細胞; osterix; osteocalcin; PTH; PTHrp受容体; 不動; 骨細胞; アポトーシス; TUNEL; ノックアウトマウス

In 2002, our data showed that trabecular bone mass and bone formation were preserved after tail-suspension in p53(-/-) mice, closely associated with ALP-positive CFU-f and mineralized nodule formation in marrow cultures obtained from tibias of p53(-/-) mice. Bone loss due to mechanical unloading can be related to the facilitation of intracellular p53-p21 signaling. We also demonstrated that generation of nitric oxide through inducible nitric oxide synthase is essential for the stimulation of bone formation upon mechanical reloading.In 2003, we clarified that skeletal unloading alleviated the anabolic action of intermittent parathyroid hormone (PTH) (1-34) in mouse tibia in association with inhibition of PTH-induced increase in c-fos mRNA in bone marrow cells. The PTH-induced increase in c-fos mRNA was depressed, but the increases in Osterix and RANKL mRNA were maintained. Unloading promoted the PTH-associated osteoclastogenesis and seemed to delay the progression of osteogenic differentiation in association with reduction of the PTH-dependent increase of c-fos mRNA in bone marrow cells.In 2004, our data demonstrated that the decreased osteogenic potential after unloading was related to the reduction of PECAM-1 (CD31) expression in bone marrow cells, and that significant increases in osteoclast surface and number after skeletal unloading were suppressed in thyroparathyroidectomized mice, closely associated with the reduction in the high expression of RANKL mRNA in the tibial bone marrow cells.Through these 3 years, we clarified that skeletal unloading reduced bone formation by the facilitation of intracellular p53-p21 signaling and the reduction of PECAM-1 expression in bone marrow cells, and that enhanced osteoclastogenesis due to skeletal unloading is related to the elevation of RANKL expression by the facilitation of parathyroid hormone signaling in bone marrow cells.

在2002年，我们的数据表明，在p53（ - / - ）小鼠中尾悬浮后，小梁骨量和骨形成保留，与ALP阳性CFU-F紧密相关，并在从p53（ - / - ）小鼠的tibias获得的骨髓培养物中与矿化结节形成密切相关。机械卸载引起的骨质流失可能与细胞内p53-P21信号的促进有关。 We also demonstrated that generation of nitric oxide through inducible nitric oxide synthase is essential for the stimulation of bone formation upon mechanical reloading.In 2003, we clarified that skeletal unloading alleviated the anabolic action of intermittent parathyroid hormone (PTH) (1-34) in mouse tibia in association with inhibition of PTH-induced increase in c-fos mRNA in bone marrow cells. PTH诱导的C-FOS mRNA的增加被抑制，但欧蛋白石和RANKL mRNA的增加。卸载促进了与PTH相关的成骨构成的发生，并且似乎延迟了成骨分化的进展，而骨髓细胞中C-FOS mRNA的c-Fos mRNA的减少相关，在2004年，我们的数据表明，卸载后的骨质降低与Pecam-1的降低相关（CD31）（CD31）的降低相关（CD31）（CD31）的降低相关（CD31）。 osteoclast surface and number after skeletal unloading were suppressed in thyroparathyroidectomized mice, closely associated with the reduction in the high expression of RANKL mRNA in the tibial bone marrow cells.Through these 3 years, we clarified that skeletal unloading reduced bone formation by the facilitation of intracellular p53-p21 signaling and the reduction of PECAM-1 expression in bone marrow cells, and由于骨骼卸载而引起的破骨质发生了，这与骨髓细胞中甲状旁腺激素信号传导的促进RANKL表达的升高有关。

项目成果

Okazaki R, Sakai A, Nakamura T, et al.: "Apoptosis and p53 expression in chondrocytes relate to degeneration in articular cartilage of immobilized knee joints"Journal of Rheumatology. (in press). 2003

Okazaki R、Sakai A、Nakamura T 等人：“软骨细胞中的细胞凋亡和 p53 表达与固定膝关节的关节软骨退化有关”风湿病学杂志。

Trabecular bone mass and bone formation are preserved after limb immobilizaion in p53 null mice.

p53 缺失小鼠肢体固定后，小梁骨量和骨形成得以保留。

• 发表时间: 2004
• 期刊: Annals of the Rheumatic Disease 63・4
• 作者: Okazaki R;Sakai A;Nakamura T;et al.
• 通讯作者: et al.

Okazaki R, Sakai A, Nakamura T, et al.: "Trabecular bone mass and bone formation are preserved after limb immobilization in p53 null mice."Annals of the Rheumatic Disease. (in press). (2004)

Okazaki R、Sakai A、Nakamura T 等人：“p53 缺失小鼠肢体固定后，小梁骨量和骨形成得以保留。”《风湿病年鉴》。

Osteoclast development in immobilized bone is suppressed by parathyroidectomy in mice.

小鼠甲状旁腺切除术可抑制固定骨中破骨细胞的发育。

• 发表时间: 2005
• 期刊: J Bone Miner Metab 23-1
• 作者: Sakai A;Nakamura T;et. al.
• 通讯作者: et. al.

Climbing exercise increases bone mass and trabecular bone turnover through transient regulation of marrow osteogenic and osteociastogenic potentials in mice.

攀岩运动通过短暂调节小鼠骨髓成骨和成骨潜能来增加骨量和骨小梁转换。

• 发表时间: 2003
• 期刊: Journal of Bone and Mineral Research 18・11
• 作者: Mori T;Sakai A;Nakamura T;et al.
• 通讯作者: et al.