中华创伤杂志
中華創傷雜誌
중화창상잡지
Chinese Journal of Traumatology
2009年
2期
177-181
,共5页
阿伦膦酸钠%骨髓问充质干细胞%丝裂原活化蛋白激酶%骨质疏松
阿倫膦痠鈉%骨髓問充質榦細胞%絲裂原活化蛋白激酶%骨質疏鬆
아륜련산납%골수문충질간세포%사렬원활화단백격매%골질소송
Alendronate%Bone marrow stromal cells%Mitogen-activated protein kinases%Osteoporosis
目的 探讨阿伦膦酸钠(Alendronate,Aln)对骨髓间充质干细胞(BMSCs)成脂分化的影响,并阐明丝裂原活化蛋白激酶(MAPK)信号通路在该过程中的作用. 方法 BMSCs取自9个月龄去势SD大鼠,分别暴露于0.01,0.1,1,10 μmol/L Aln.成脂诱导2周后进行油红O染色和镜下计数分析,RT-PCR检测过氧化物酶体增殖体激活受体γ2(PPARγ2)表达;使用MAPK通路特异性抑制剂并诱导2周后再观察PPARγ2表达情况,Western blot观察Aln对MAPK通路表达的影响. 结果 BMSCs成脂诱导2周后,油红O染色阳性细胞数随着药物浓度的增高而显著减少(P<0.01).PPARγ2表达随着药物浓度的增高而显著降低.分别使用ERK1/2、JNK抑制剂PD98059和SP600125并诱导2周后,PPARγ2表达上调;使用p38抑制剂SB203580并诱导2周后,PPARγ2表达下调.Western blot结果显示,Aln在5,15,30 min时上调P-ERK1/2和P-JNK的表达,分别使用抑制剂后,表达下调. 结论 Aln通过激活ERK1/2和JNK信号通路,而不是p38,发挥抑制去势大鼠来源的BMSCs成脂分化作用,其效应具有浓度依赖性.
目的 探討阿倫膦痠鈉(Alendronate,Aln)對骨髓間充質榦細胞(BMSCs)成脂分化的影響,併闡明絲裂原活化蛋白激酶(MAPK)信號通路在該過程中的作用. 方法 BMSCs取自9箇月齡去勢SD大鼠,分彆暴露于0.01,0.1,1,10 μmol/L Aln.成脂誘導2週後進行油紅O染色和鏡下計數分析,RT-PCR檢測過氧化物酶體增殖體激活受體γ2(PPARγ2)錶達;使用MAPK通路特異性抑製劑併誘導2週後再觀察PPARγ2錶達情況,Western blot觀察Aln對MAPK通路錶達的影響. 結果 BMSCs成脂誘導2週後,油紅O染色暘性細胞數隨著藥物濃度的增高而顯著減少(P<0.01).PPARγ2錶達隨著藥物濃度的增高而顯著降低.分彆使用ERK1/2、JNK抑製劑PD98059和SP600125併誘導2週後,PPARγ2錶達上調;使用p38抑製劑SB203580併誘導2週後,PPARγ2錶達下調.Western blot結果顯示,Aln在5,15,30 min時上調P-ERK1/2和P-JNK的錶達,分彆使用抑製劑後,錶達下調. 結論 Aln通過激活ERK1/2和JNK信號通路,而不是p38,髮揮抑製去勢大鼠來源的BMSCs成脂分化作用,其效應具有濃度依賴性.
목적 탐토아륜련산납(Alendronate,Aln)대골수간충질간세포(BMSCs)성지분화적영향,병천명사렬원활화단백격매(MAPK)신호통로재해과정중적작용. 방법 BMSCs취자9개월령거세SD대서,분별폭로우0.01,0.1,1,10 μmol/L Aln.성지유도2주후진행유홍O염색화경하계수분석,RT-PCR검측과양화물매체증식체격활수체γ2(PPARγ2)표체;사용MAPK통로특이성억제제병유도2주후재관찰PPARγ2표체정황,Western blot관찰Aln대MAPK통로표체적영향. 결과 BMSCs성지유도2주후,유홍O염색양성세포수수착약물농도적증고이현저감소(P<0.01).PPARγ2표체수착약물농도적증고이현저강저.분별사용ERK1/2、JNK억제제PD98059화SP600125병유도2주후,PPARγ2표체상조;사용p38억제제SB203580병유도2주후,PPARγ2표체하조.Western blot결과현시,Aln재5,15,30 min시상조P-ERK1/2화P-JNK적표체,분별사용억제제후,표체하조. 결론 Aln통과격활ERK1/2화JNK신호통로,이불시p38,발휘억제거세대서래원적BMSCs성지분화작용,기효응구유농도의뢰성.
Objective To explore the effects of alendronate on adipogenic differentiation of bone marrow stremal cells (BMSCs) and the role of mitogen-activated protein kinases (MAPK) signal pathway in this process. Methods BMSCs were derived from 9-month-old ovariectomized SD rats and exposed to 0.01, 0.1, 1, 10 μmol/L of alendronate for 2 weeks. The number of BMSCs was counted under light microscope after oil red O staining. The expression of peroxisome proliferators activated receptor-γ, 2 (PPAR-γ2) was measured by RT-PCR. The effect of alendronate on MAPK signal pathway was detected by Western blot. Results After two weeks of induction of BMSCs by alendronate, BMSCs with positive oil red O staining significantly decreased as the increase of the concentration of alendronate (P <0.01), so did the expression of PPAR-γ2. The expression level of PPAR 2 increased when exposing BMSCs to ERK1/2 or JNK specific inhibitors, PD98059 and SP600125 for two weeks. However, the expression level of PPAR 2 decreased when exposing BMSCs to SB203580 (an inhibitor of p38) for two weeks. Condusion Alendronate can inhibit adipogenic differentiation of BMSCs derived from ovariectomized rats in a doso-dependent manner by activating ERK1/2 and JNK rather than p38.
