Molecular basis on bone growth disturbance : Novel treatment for achondroplasia

骨生长障碍的分子基础：软骨发育不全的新疗法

• 批准号: 14570747
• 负责人: INOUE Masaru
• 金额: $ 2.3万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 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-14570747/
• 关键词: achondroplasia; PTH; FGFR3; bone growth; 軟骨細胞; アポトーシス; FGF receptor 3; STAT1; 骨成長障害; Stat1

Achondroplasia (ACH) is the most common form of genetic short statue. Recently we treat them with human growth hormone but its effect is limited. To explore new therapeutic applications, we performed PTH treatment for ACH model mouse (AchTG).[Short-term-trial] Wild (WT) and AchTG were treated with daily PTH subcutaneous injection (100μ/kg,1000μ/kg or vehicle) during day 7 to 20, then at day 21, their femurs were dissected, measured their length and analyzed histologically. [Long-term-trial] WT and AchTG mouse were treated with 3-times/week PTH subcutaneous injection (100μ/kg) during 1^<st> to 5^<th> week, then at day 42, their femurs, tibias, radiuses and humeruses were dissected, measured their length and analyzed histologically.AchTG femurs were significantly disturbed in longitudinal bone growth compared with WT ones. PTH significantly improved bone growth of AchTG but of WT. Histologically, PTH expands growth plate in both AchTG and WT femurs in short-term-trial but in long-term-trial.We confirmed that constitutive active FGFR3 mutation suppressed bone growth in transgenic mice and that PTH rescued bone from the growth disturbance. Our results suggest that PTH has potential to rescue the bone growth disturbance in achondroplasia.

软骨发育不全（ACH）是遗传性矮小最常见的形式。最近，我们用人类生长激素治疗他们，但效果有限。为了探索新的治疗应用，我们对ACH模型小鼠（AchTG）进行了PTH治疗。[短期试验]在第7天至第20天期间，每天皮下注射PTH（100μ/kg、1000μ/kg或赋形剂）处理野生型（WT）和AchTG，然后在第21天，解剖它们的股骨，测量它们的长度并进行组织学分析。[长期试验]将WT和AchTG小鼠皮下注射PTH（100μ g/kg）3次/周，共1 <st>~ 5周<th>，然后在第42天解剖其股骨、胫骨、桡骨和肱骨，测量其长度并进行组织学分析。PTH显著改善AchTG的骨生长，但WT。组织学上，PTH在短期试验中扩张AchTG和WT股骨的生长板，但在长期试验中，我们证实了组成性活性FGFR 3突变抑制转基因小鼠的骨生长，PTH从生长障碍中拯救骨。我们的研究结果表明，甲状旁腺素有可能挽救软骨发育不全的骨生长障碍。

项目成果

骨の病気と付き合うには -本人と家族のために-

如何与骨病共存 - 为了您自己和您的家人 -

• 发表时间: 2004
• 作者: 清野佳紀監修;山中良孝編
• 通讯作者: 山中良孝編

Yamashita N., Tanaka H., et al.: "Analysis of linear growth in survivors of childhood acute lymphoblastic leukemia"Journal of Bone and Mineral Metabolism. 21. 172-178 (2003)

Yamashita N.、Tanaka H. 等人：“儿童急性淋巴细胞白血病幸存者的线性生长分析”骨与矿物质代谢杂志。

Yoshitaka Yamanaka, et al.: "PTH-P Rescues ATDC5 Cells from Apoptosis Induced by F6F Receptor 3 Mutation"Journal of Bone and Mineral Research. (in press).

Yoshitaka Yamanaka 等人：“PTH-P 拯救 ATDC5 细胞免受 F6F 受体 3 突变诱导的凋亡”，骨与矿物质研究杂志。

Yamanaka Y., et al.: "Molecular basis for treatment of achondroplasia"Hormone Research. 60. 60-64 (2003)

Yamanaka Y.等人：“治疗软骨发育不全的分子基础”激素研究。

Direct action of 1,25-dihydroxyvitamin D on bone: VDRKO bone shows excessive bone formation in normal mineral condition

• DOI: 10.1016/j.jsbmb.2004.03.021
• 发表时间: 2004-05-01
• 期刊: JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
• 影响因子: 4.1
• 作者: Tanaka, H;Seino, Y
• 通讯作者: Seino, Y