Investigation of mechanism of bone formation associated with aging

衰老相关骨形成机制的研究

• 批准号: 04454454
• 负责人: YOSHIKI Shusaku
• 金额: $ 4.35万
• 依托单位: Showa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04454454/
• 关键词: bone; osteoblast; aiging; cell culture; bone matrix; gene expression

To investigate the mechanism involved in the changes in bone tissues associated with aging, we conducted the following experiments.1)Age-related reduction in bone matrix protein mRNA in rat bone tissueAge-related changes in the expression of bone matrix protein mRNAs in individual osteoblastic cells were analyzed in vivo by in situ hybridization using undecalcified bone sections. In the femurs of 8-week-old male rats, strong expression of type I collagen and osteocalcin mRNAs was detected in cuboidal osteoblasts on the bone surface. Osteopontin mRNA was detected in some of the mononuclear cells and osteoclasts on the bone resorption surface. In the femurs of 60-week-old and 100-week-old male rats, expression these bone matrix protein mRNAs was markedly decreased. These results indicate age-related reductions in both biological activity and numbers of osteoblasts.Properties of osteoprogenitor cells in bone marrow of aged ratsTo investigate the mechanism of bone loss associated woth aging, we examined the properties of rat bone marrow cells including Colony Forming Unit-Fibroblastic (CFU-F) which contains osteoprogenitor cells. The following results were obtained.1)Both alkaline phosphatase (ALP) activity and parathyroid hormone response in bone marrow cells were decreased with age. 2) Both the total number of CFU-F and the ALP-positive CFU-F were decreased with age. 3) Nine out of 10 CFU-Fs isolated from 4-week-old rats form bone-like tissues when they were transplanted into rat peritoneal cavity using diffusion chambers. However, only 3 out of 6 CFU-Fs isolated from 60-week-old rats form bone-like tissues. These results suggest that decrease in number of osteoprogenitor cells is involed, at least in part, in the mechanizm of senile osteoporosis.

为了研究与衰老相关的骨组织变化的机制，我们进行了以下实验。1）大鼠骨组织中骨基质蛋白mRNA的骨钙素相关减少通过使用未脱钙骨切片的原位杂交，在体内分析了单个成骨细胞中骨基质蛋白mRNA表达的骨钙素相关变化。在8周龄雄性大鼠股骨中，在骨表面的立方成骨细胞中检测到I型胶原和骨钙素mRNA的强表达。骨桥蛋白mRNA在骨吸收表面的一些单核细胞和破骨细胞中检测到。在60周龄和100周龄雄性大鼠股骨中，这些骨基质蛋白mRNA的表达显著降低。这些结果表明成骨细胞的生物学活性和数量均随着年龄的增长而降低。老年大鼠骨髓中骨祖细胞的特性为了研究与年龄相关的骨丢失的机制，我们检测了大鼠骨髓细胞的特性，包括含有骨祖细胞的集落形成单位-成纤维细胞（CFU-F）。结果表明：（1）骨髓细胞碱性磷酸酶（ALP）活性和甲状旁腺激素反应均随年龄增长而降低。2)CFU-F总数和ALP阳性CFU-F均随年龄增长而减少。3)从4周龄大鼠分离的10个CFU-Fs中有9个在扩散池中移植到大鼠腹腔后形成骨样组织。然而，从60周龄大鼠分离的6个CFU-F中只有3个形成骨样组织。提示骨祖细胞数量的减少至少部分参与了老年性骨质疏松症的发病机制。

项目成果

T.Ikeda et al.: "In situ bybridization of bone matrix proteins in undecalcified aclutt rat bone sections" J,Histochem.Cytochem.40. 1079-1088 (1992)

T.Ikeda 等人：“未脱钙 aclutt 大鼠骨切片中骨基质蛋白的原位杂交”J，Histochem.Cytochem.40。

Y.Nakamura et al: "Acid phosphatase activity is chitected preferenfeally in osteoclastic lineage by pre-treatment wite cyanuric chloride" J,Histochem.Cytochem.39. 1415-1420 (1991)

Y.Nakamura 等人：“通过用氰尿酰氯预处理，在破骨细胞谱系中优先考虑酸性磷酸酶活性”J，Histochem.Cytochem.39。