Osteogenic and angiogenic activity of hypertrophic chondrocytes and its clinical application

肥大软骨细胞的成骨和血管生成活性及其临床应用

• 批准号: 15592097
• 负责人: MORI Yoshiyuki
• 金额: $ 2.11万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15592097/
• 关键词: cartilage; hypertrophy; angiogenesis; osteogenesis

1.Establishment of the method to differentiate isolated mesenchymal stromal cells into chondrocytesWe isolated mesenchymal stromal cells from a transgenic mouse line which expressed green fluorescent protein (GFP) under the control of the osteoblast-specific type I collagen promoter. Using these cells as a detector, we screened combinations of various chondrogenic factors for the optimal signaling. As a result, we identified the combination of Sox5, Sox6, and Sox9 was the most efficient and cell-type independent signaling unit. Treatment with the combination induced mRNA expression of cartilage marker genes, such as type II collagen, type IX collagen, and type XI collagen, aggrecan, and cbondromodulin-1. The treatment also induced expression of cartilage-specific matrix detected by immunohistuchemistry for type II Collagen and toluidine Blue stainin2.Establishment of the method to induce hypertcophic differentiation of chondrocytesWe treated chondrocyte-differentiated mesenchymal stromal cells, a undifferentiated mesenchymal cell line C3H10T1/2, and primary rib chondrocytes with various signaling molecules to find out that the canonical Wnt signaling pathway and Runx2 signaling pathway promoted hypertrophic differentiation detected by real-time RT-PCRT for type X collagen. In contrast, the loss of the gene endoding a stimulatory G protein, a putative inhibitory factor for hypertrophy, resulted in accelerated hypertrophy of chondrocytes in vivo.3.Induction of angiogenesis and osteogenesis by mineralized hypertrophic chondrocytesWe isolated chondrocytes from rabbit ribs and treated them with the canonical Wnt signal in osteogenic medium to induce hypertrophic differentiation and calcification. We formed pellets from these cells and transplanted subcutaneously into the back of rabbits. Angiogenesis into the pellets was observed at 2 weeks after the surgery. At 4 weeks after the surgery, osteogenesis occurred with bone marrow space.

1.间充质基质细胞向软骨细胞分化方法的建立我们从转基因小鼠中分离了间充质基质细胞，该转基因小鼠在成骨细胞特异性I型胶原启动子的控制下表达绿色荧光蛋白（GFP）。使用这些细胞作为检测器，我们筛选了各种软骨形成因子的组合，以获得最佳信号。因此，我们鉴定了Sox 5、Sox 6和Sox 9的组合是最有效的且与细胞类型无关的信号单元。用该组合处理诱导软骨标记基因的mRNA表达，所述软骨标记基因例如II型胶原、IX型胶原和XI型胶原、聚集蛋白聚糖和软骨调节蛋白-1。2.诱导软骨细胞向肥大细胞分化方法的建立我们将软骨细胞分化的间充质基质细胞，一种未分化的间充质细胞系C3 H10 T1/2，和具有各种信号分子的原代肋骨软骨细胞，以发现经典Wnt信号通路和Runx 2信号通路促进通过实时RT-PCR检测的肥大分化。X型胶原蛋白的PCRT。相反，编码刺激性G蛋白（一种肥大的抑制因子）的基因的缺失导致体内软骨细胞加速肥大。3.矿化肥大软骨细胞诱导血管生成和成骨我们从兔肋骨分离软骨细胞，并在成骨培养基中用经典Wnt信号处理它们以诱导肥大分化和钙化。我们将这些细胞制成小球，并皮下移植到兔子的背部。在手术后2周观察到颗粒中的血管生成。术后4周，骨髓间隙出现成骨。

项目成果

自己フィブリン糊の応用-自己血輸血実施上のマネジメント

自体纤维蛋白胶的应用-自体输血的管理

• 发表时间: 2003
• 期刊: 口腔外科領域の自己血輸血実施上の留意点-総貯血量に基づく採血計画
• 作者: 森 良之;高戸 毅
• 通讯作者: 高戸 毅

歯科用キシロカイン^<【○!R】>中に含まれるピロ亜硫酸ナトリウムによるアナフィラキシーショックの1例

牙科用利多卡因中含有的焦亚硫酸钠引起过敏性休克一例^<【○!R】>

• 发表时间: 2003
• 期刊: 日本口腔外科学会雑誌 49(3)
• 作者: 西條英人;西川久美子;森 良之;小泉敏之;坂田康彰;高戸 毅
• 通讯作者: 高戸 毅

General medical sciense 「Zettusyo」

一般医学“Zettusyo”

• 发表时间: 2004
• 作者: Yano;F et al.;Mori Y
• 通讯作者: Mori Y

Secondary correction of wide nasal root of bilateral cleft-associated nasal deformity in Orientals.

东方人双侧鼻裂相关鼻畸形宽鼻根的二次矫正。

• 发表时间: 2003
• 期刊: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery 37
• 作者: Omori M.;Takato T.;Eguchi T.;Mori Y.;Tomizuka K.
• 通讯作者: Tomizuka K.

Stimulatory G protein (Gs) directly regulates hypertrophic differentiation of growth plate cartilage in vivo.

刺激性G蛋白（Gs）直接调节体内生长板软骨的肥大分化。

• 发表时间: 2004
• 期刊: Proc Nat Acad Sci USA 101
• 作者: Bastepe M;Weinstein LS;Ogata N;Kawaguchi H;Juppner H;Kronenberg HM;Chung U.
• 通讯作者: Chung U.