【摘要】：骨和軟骨損傷是常見(jiàn)的運(yùn)動(dòng)系統(tǒng)疾患,組織工程技術(shù)構(gòu)建人工骨和軟骨,以及再生醫(yī)學(xué)技術(shù)促進(jìn)骨和軟骨再生是其有效治療方法。p oly(lactic-co-glycolic acid) (PLGA)和poly-L-lactate acid (PLLA)等乳酸基質(zhì)材料是骨-軟骨損傷修復(fù)與再生常用的支架材料和藥物載體,乳酸是其合成的基質(zhì)材料也是其體內(nèi)降解的主要產(chǎn)物。有研究顯示PLGA和PLLA的降解產(chǎn)物可影響“骨-軟骨”組織功能,但是乳酸在“骨-軟骨”組織中的功能尚不清楚。本課題將研究乳酸對(duì)軟骨細(xì)胞(骨關(guān)節(jié)炎(OA)及正常軟骨細(xì)胞)以及骨組織細(xì)胞(骨髓間充質(zhì)干細(xì)胞,MSC)的作用。研究共分2部分：1乳酸影響軟骨細(xì)胞穩(wěn)態(tài)的研究以生物材料為支架的組織工程再生技術(shù)和自體軟骨細(xì)胞移植技術(shù)是治療軟骨缺損的有效方法,但這兩種技術(shù)都存在缺陷：PLGA和PLLA等常用生物支架降解后影響軟骨功能；軟骨細(xì)胞體外培養(yǎng)易發(fā)生去表型丟失。本實(shí)驗(yàn)研究PLGA和PLLA的主要降解產(chǎn)物乳酸對(duì)OA軟骨細(xì)胞的調(diào)控作用及其機(jī)制,為后期優(yōu)化用于軟骨再生的PLGA和PLLA支架材料設(shè)計(jì)提供理論支持；以乳酸作用于體外培養(yǎng)的正常軟骨細(xì)胞,檢測(cè)其對(duì)軟骨細(xì)胞表型維持的作用,為軟骨細(xì)胞體外培養(yǎng)表型維持提供新方法。1.1適宜乳酸作用抑制骨關(guān)節(jié)炎軟骨細(xì)胞的病理進(jìn)程我們檢測(cè)了不同分子量的PLGA和PLLA降解液中乳酸的濃度,并以降解液作用于人軟骨細(xì)胞,檢測(cè)其對(duì)軟骨細(xì)胞增殖和基質(zhì)蛋白基因表達(dá)的作用；以不同濃度和時(shí)間的乳酸作用于人正常及OA軟骨細(xì)胞,檢測(cè)細(xì)胞的功能變化；將乳酸分別以脈沖式和一次性模式作用于軟骨細(xì)胞,優(yōu)化其最佳作用效果；采用基因芯片篩選并基因敲降方法,驗(yàn)證乳酸調(diào)控細(xì)胞功能的可能機(jī)制。具體研究?jī)?nèi)容如下：第一部分、PLGA和PLLA降解液對(duì)人軟骨細(xì)胞的作用。主要發(fā)現(xiàn)：1)不同分子量PLGA和PLLA降解液對(duì)軟骨細(xì)胞增殖和COL2A1和ACAN的表達(dá)作用不同。2)不同分子量P LGA和PLLA降解液中乳酸濃度和pH值不同,分子量越小,乳酸濃度越高,pH值越低。第二部分、乳酸對(duì)人軟骨細(xì)胞的作用。主要發(fā)現(xiàn)：乳酸對(duì)人軟骨細(xì)胞的作用呈時(shí)間和濃度依賴性,短時(shí)高濃度乳酸可促進(jìn)COL2A1和ACAN的表達(dá)；并且短時(shí)高濃度乳酸還可抑制ADAMTS5的表達(dá)。第三部分、乳酸不同作用模式對(duì)軟骨細(xì)胞的效果。結(jié)果發(fā)現(xiàn)3天中每天1次,每次8小時(shí)的乳酸脈沖式作用模式,相比3天僅給予1次8小時(shí)乳酸的一次性作用模式,可顯著上調(diào)COL2A1的表達(dá)。第四部分、乳酸對(duì)軟骨細(xì)胞的作用機(jī)制。主要發(fā)現(xiàn)：1)通過(guò)基因芯片篩查乳酸作用后軟骨細(xì)胞的基因表達(dá)和生物過(guò)程變化,發(fā)現(xiàn)低氧誘導(dǎo)因子1A (hypoxia inducible factor 1A, HIF1A)下游調(diào)控基因差異顯著,提示HIF1A參與調(diào)控乳酸對(duì)軟骨細(xì)胞的作用。2)通過(guò)敲降HIF1A及其家族成員低氧誘導(dǎo)因子2A (hypoxia inducible factor 2A, HIF2A)方法,發(fā)現(xiàn)乳酸的作用主要由HIF1A介導(dǎo)而非HIF2A;且發(fā)現(xiàn)乳酸調(diào)控的HIF1A蛋白表達(dá)增強(qiáng)主要是由于上調(diào)其基因表達(dá),而非抑制其蛋白降解。上述結(jié)果表明,適宜的乳酸作用可通過(guò)上調(diào)COL2A1和抑制ADAMTS5的表達(dá),促進(jìn)軟骨細(xì)胞的穩(wěn)態(tài)；設(shè)計(jì)用于軟骨再生的PLGA和PLLA材料時(shí)需考慮降解產(chǎn)物乳酸的影響。1.2適宜乳酸作用促進(jìn)體外培養(yǎng)的正常軟骨細(xì)胞的表型維持我們以1.1中篩選的乳酸最佳作用濃度和時(shí)間作用于人軟骨細(xì)胞,檢測(cè)其對(duì)軟骨細(xì)胞表型維持的作用；從乳酸調(diào)控軟骨細(xì)胞糖酵解代謝角度,闡釋乳酸促進(jìn)表型維持的機(jī)制。具體研究?jī)?nèi)容如下：第一部分、乳酸對(duì)軟骨細(xì)胞表型維持的作用。主要發(fā)現(xiàn)：原代軟骨細(xì)胞傳代過(guò)程中COL2A1、AcAN和SOX9的表達(dá)持續(xù)下降,乳酸作用可上調(diào)COL2A1、ACAN和SOX9的表達(dá),維持軟骨細(xì)胞表型。第二部分、乳酸維持軟骨細(xì)胞表型的機(jī)制。主要發(fā)現(xiàn)：1)乳酸可上調(diào)軟骨細(xì)胞糖酵解相關(guān)基因表達(dá)。2)軟骨細(xì)胞表型與糖酵解相關(guān)：低氧和TGF-β3作用可上調(diào)糖酵解,傳代過(guò)程中糖酵解下調(diào)。3)抑制糖酵解后,乳酸調(diào)控軟骨細(xì)胞表型的功能下降。上述結(jié)果表明,乳酸可通過(guò)上調(diào)糖酵解促進(jìn)軟骨細(xì)胞體外培養(yǎng)過(guò)程中的表型維持。2乳酸調(diào)控骨髓間充質(zhì)干細(xì)胞的自我更新能力的研究骨髓間充質(zhì)干細(xì)胞是骨組織的主要前體細(xì)胞。間充質(zhì)干細(xì)胞的一個(gè)顯著特征是具有自我更新能力,研究顯示細(xì)胞代謝可通過(guò)不同的代謝中間產(chǎn)物調(diào)控干細(xì)胞自我更新能力。乳酸是PLGA、PLLA的降解產(chǎn)物,也是細(xì)胞無(wú)氧酵解代謝的主要終產(chǎn)物,其對(duì)干細(xì)胞的自我更新能力的調(diào)控尚不清楚。本實(shí)驗(yàn)研究乳酸對(duì)于細(xì)胞自我更新能力的作用,并從KDM6B調(diào)控糖酵解角度探討乳酸調(diào)控干細(xì)胞的自我更新能力的機(jī)制,以增加乳酸調(diào)控干細(xì)胞功能的新認(rèn)識(shí)。具體研究?jī)?nèi)容如下：第一部分、乳酸對(duì)hMSC的增殖與自我更新能力的作用。主要發(fā)現(xiàn)：1)乳酸抑制hMSC的增殖。2)低濃度乳酸促進(jìn)hMSC的自我更新能力。3)乳酸促進(jìn)hMSC干性基因表達(dá)。第二部分、乳酸調(diào)控]MSC自我更新能力的機(jī)制(乳酸對(duì)糖酵解的調(diào)控)。主要發(fā)現(xiàn)：1)乳酸可上調(diào)hMSC糖酵解。2)調(diào)控糖酵解可影響hMSC的自我更新能力：上調(diào)糖酵解可促進(jìn)hMSC的自我更新能力,下調(diào)糖酵解可抑制hMSC的自我更新能力。3)抑制糖酵解后,乳酸調(diào)控hMSC的自我更新能力下降。第三部分、乳酸對(duì)糖酵解的調(diào)控機(jī)制(乳酸對(duì)KDM6B的調(diào)控)。主要發(fā)現(xiàn)：1)乳酸可上調(diào)KDM6B的表達(dá)。2)KDM6B調(diào)控1MSC糖酵解和自我更新能力：KDM6B敲降可下調(diào)hMSC糖酵解,KDM6B敲降可抑制hMSC自我更新能力。3)敲降KDM6B后,乳酸調(diào)控hMSC的自我更新能力下降。上述結(jié)果表明,乳酸可通過(guò)KDM6B介導(dǎo)的糖酵解調(diào)控hMSC的自我更新能力。
[Abstract]:Bone and cartilage damage is a common system disorder, tissue engineering techniques to construct artificial bone and cartilage, and regenerative medicine to promote bone and cartilage regeneration is an effective method of treatment. The lactic acid matrix material such as p-toly (lactic-co-glycolic acid) (PLGA) and poly-L-lacate acid (PLLA) is a commonly used scaffold material and drug carrier for the repair and regeneration of bone-cartilage damage. Studies have shown that the degradation products of PLGA and PLLA may affect the "bone-cartilage" tissue function, but the function of lactic acid in the "bone-cartilage" tissue is not clear. This subject will study the effect of lactic acid on chondrocytes (OA) and normal cartilage cells) and bone tissue cells (bone marrow mesenchymal stem cells, MSC). The research is divided into two parts:1 lactic acid influences the steady state of the cartilage cell, and the tissue engineering regeneration technology and the autocartilage cell transplantation technology of the biological material as the support are effective methods for treating the cartilage defect, but the two technologies have the defects that: The cartilage function is affected by the degradation of the common biological scaffold, such as PLGA and PLLA, and the in vitro culture of the chondrocytes is susceptible to the loss of the phenotype. The effect and mechanism of lactic acid on OA chondrocytes in PLGA and PLLA were studied in this experiment. The theoretical support was provided for the design of PLGA and PLLA scaffolds for cartilage regeneration in the later stage, and the normal chondrocytes cultured in vitro by lactic acid. it is suitable for lactic acid to inhibit the pathological process of the osteoarthritis cartilage cell, and the lactic acid concentration in the PLGA and the PLLA degradation liquid with different molecular weights is detected, and the degradation liquid acts on the human cartilage cell to detect the effect of the degradation liquid on the proliferation of the chondrocyte and the expression of the basic protein gene, and the lactic acid acting on the human normal and the OA cartilage cells at different concentrations and times is used for detecting the function change of the cells; The lactic acid is applied to the chondrocytes in a pulse mode and a one-time mode respectively, and the optimal action effect thereof is optimized; a gene chip is adopted to screen and the gene knock-down method, and the possible mechanism of the function of the lactic acid regulation and control cell is verified. The specific contents of the study are as follows: The first part, PLGA and PLLA degradation liquid have effect on human chondrocytes. The results were as follows:1) The different molecular weight of PLGA and PLLA degradation solution to the proliferation of chondrocytes and the expression of COL2A1 and ACAN.2) The concentration of lactic acid and the pH value in the different molecular weight of P-LGA and PLLA-degrading liquid were different, the smaller the molecular weight, the higher the lactic acid concentration, and the lower the pH value. The second part, the effect of lactic acid on the human chondrocytes. It is found that the effect of lactic acid on the human chondrocytes is time and concentration dependent, and the short-term high-concentration lactic acid can promote the expression of COL2 A1 and ACAN, and the short-term high-concentration lactic acid can also inhibit the expression of the ADAMTS5. The third part, the effect of the different modes of lactic acid on the chondrocytes. The results show that the expression of COL2A1 can be up-regulated by one-time mode of one-time action of 8-hour lactic acid only once every 8 hours in 3 days. The fourth part is the mechanism of the action of lactic acid on the chondrocytes. It was found that:1) The gene expression and the biological process of the chondrocytes after the lactic acid action were screened by the gene chip, and the difference of the regulatory genes downstream of the hypoxia-inducible factor 1A (HIF1A) was found to be significant. HIF1A was suggested to be involved in the regulation of the effect of lactic acid on the chondrocyte.2) The effect of lactic acid was found to be mainly mediated by HIF1A and not HIF2A by the method of HIF1A and its family member hypoxia inducible factor 2A (HIF2A). And the expression of the HIF1A protein regulated by lactic acid is found to be mainly due to the up-regulation of the gene expression and the non-inhibition of the protein degradation. The results show that the appropriate lactic acid action can promote the steady state of the chondrocytes by up-regulating the expression of COL2 A1 and inhibiting the expression of the ADAMTS5. The effect of the degradation product lactic acid needs to be taken into account when designing the PLGA and PLLA materials for cartilage regeneration. The mechanism of lactic acid to promote the maintenance of the phenotype was explained. The specific contents of the study are as follows: The first part, the effect of lactic acid on the phenotype of the chondrocyte. It was found that the expression of COL2A1, AAN and SOX9 decreased continuously during the passage of primary chondrocytes, and the expression of COL2A1, ACAN and SOX9 could be up-regulated by lactic acid, and the phenotype of chondrocyte was maintained. The second part, the mechanism of the lactic acid maintenance of the chondrocyte phenotype. It is found that 1) lactic acid can increase the expression of the related gene of the glycolysis of the chondrocyte.2) The phenotype of the chondrocyte is related to the glycolysis: the action of hypoxia and TGF-3 can increase the glycolysis, and the glycolysis in the course of the passage is down-regulated.3) After the glycolysis is inhibited, The function of lactic acid to regulate the phenotype of the chondrocyte decreased. The results show that lactic acid can promote the phenotype of the in vitro culture of the chondrocytes by up-regulation of glycolysis. The study of the self-renewal ability of the lactic acid to regulate the self-renewal of the bone marrow-derived mesenchymal stem cells is the main precursor of the bone tissue. A significant feature of the mesenchymal stem cells is the ability to self-update, and the study shows that cell metabolism can regulate the self-renewal capacity of stem cells through different metabolic intermediates. The lactic acid is the degradation product of PLGA and PLLA, and it is the main end product of the anaerobic glycolysis of the cell. The regulation of the self-renewal ability of the stem cells is not clear. In this experiment, the role of lactic acid on the self-renewal ability of the cells was studied, and the mechanism of the self-renewal capacity of the lactic acid-regulating stem cells was discussed from the viewpoint of the control of the glycolysis of the KDM6B, so as to increase the new recognition of the function of the lactic acid to regulate the stem cells. The specific content of the study is as follows: The first part, the effect of lactic acid on the proliferation and self-renewal capacity of hMSCs. 1) The lactic acid inhibits the proliferation of hMSCs.2) The low concentration of lactic acid promotes the self-renewal capacity of hMSCs.3) The lactic acid promotes the expression of hMSCs. The second part, the mechanism of the self-renewal capacity of the MSC (the regulation of the glycolysis of the lactic acid). it is found that 1) lactic acid can increase the glycolysis of hMSCs.2) The regulation of glycolysis can affect the self-renewal ability of hMSCs: up-regulation of glycolysis can promote the self-renewal capacity of hMSCs, and the down-regulation of glycolysis can inhibit the self-renewal capacity of hMSCs.3) After the glycolysis is inhibited, The self-renewal ability of the hMSCs was decreased by lactic acid. The third part, the control mechanism of the lactic acid to glycolysis (the regulation of the lactic acid to the KDM6B). It is found that 1) lactic acid can increase the expression of KDM6B.2) KDM6B regulates the glycolysis and self-renewal capacity of the 1MSC: the KDM6B knock-down can reduce the glycolysis of hMSCs, and the KDM6B knock-down can inhibit the self-renewal capacity of hMSCs.3) After the KDM6B is knocked down, the self-renewal ability of the hMSCs is reduced. The results show that lactic acid can regulate the self-renewal capacity of hMSC through the glycolysis mediated by KDM6B.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R68;R318.08

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 何清義,李起鴻,許建中,楊柳;轉(zhuǎn)化軟骨細(xì)胞與正常軟骨細(xì)胞的生物特性比較[J];中國(guó)臨床康復(fù);2002年10期

2 王小虎;衛(wèi)小春;陳維毅;;軟骨細(xì)胞力學(xué)特性的研究進(jìn)展[J];中華醫(yī)學(xué)雜志;2006年21期

3 沈雁,唐毅,李斯明,鐘燦燦,梁佩紅;堿性成纖維細(xì)胞生長(zhǎng)因子與透明質(zhì)酸對(duì)培養(yǎng)兔軟骨細(xì)胞的作用[J];中華創(chuàng)傷雜志;2000年06期

4 林建華,吳朝陽(yáng),許衛(wèi)紅;不同培養(yǎng)時(shí)間軟骨細(xì)胞的生物學(xué)特性[J];福建醫(yī)科大學(xué)學(xué)報(bào);2000年02期

5 張文濤,盧世璧,黃英,李楠;軟骨細(xì)胞形態(tài)對(duì)其縫隙連接的影響[J];中國(guó)創(chuàng)傷骨科雜志;2000年04期

6 楊物鵬,許建中;軟骨細(xì)胞培養(yǎng)及其調(diào)控[J];中國(guó)矯形外科雜志;2000年08期

7 楊彩榮;軟骨細(xì)胞培養(yǎng)及其調(diào)控因素研究進(jìn)展[J];國(guó)外醫(yī)學(xué).耳鼻咽喉科學(xué)分冊(cè);2002年03期

8 張文濤,盧世璧,黃英,李楠;軟骨細(xì)胞形態(tài)、表型與胞間通訊研究[J];中國(guó)修復(fù)重建外科雜志;2002年05期

9 楊運(yùn)東 ,陳基長(zhǎng);不同施加因素對(duì)軟骨細(xì)胞的影響[J];中醫(yī)正骨;2002年09期

10 張艷,柴崗,崔磊,劉偉,曹誼林;不同類型人軟骨細(xì)胞體外生物學(xué)特性比較[J];中華實(shí)驗(yàn)外科雜志;2003年06期

相關(guān)會(huì)議論文 前10條

1 張春雷;孫美樂(lè);姚洪菊;;抗氧化劑和透明質(zhì)酸對(duì)軟骨細(xì)胞的保護(hù)作用[A];中國(guó)細(xì)胞生物學(xué)學(xué)會(huì)第五次會(huì)議論文摘要匯編[C];1992年

2 任宏造;;軟骨細(xì)胞的超生結(jié)構(gòu)病理[A];第六次全國(guó)電子顯微學(xué)會(huì)議論文摘要集[C];1990年

3 張楊;崔麗;郭悅;孫曉雷;李秀蘭;;滑膜細(xì)胞微環(huán)境對(duì)軟骨細(xì)胞生物學(xué)活性的影響[A];第十八屆全國(guó)中西醫(yī)結(jié)合骨傷科學(xué)術(shù)研討會(huì)論文匯編[C];2011年

4 柏濤;;骨髓間充質(zhì)干細(xì)胞誘導(dǎo)表達(dá)軟骨細(xì)胞表型的研究進(jìn)展[A];玉溪市第三屆二次骨科學(xué)術(shù)研討會(huì)論文匯編[C];2009年

5 周紅輝;萬(wàn)福生;;人骨髓間充質(zhì)干細(xì)胞分化為軟骨細(xì)胞的實(shí)驗(yàn)研究[A];華東六省一市生物化學(xué)與分子生物學(xué)學(xué)會(huì)2006年學(xué)術(shù)交流會(huì)論文集[C];2006年

6 王正輝;吳寶俊;許珉;;殼聚糖/明膠復(fù)合不同軟骨細(xì)胞體外構(gòu)建組織工程軟骨的實(shí)驗(yàn)研究[A];全國(guó)耳鼻咽喉頭頸外科中青年學(xué)術(shù)會(huì)議論文匯編[C];2012年

7 馬劍雄;馬信龍;張華鋒;張園;王志鋼;楊陽(yáng);;生物力學(xué)因素在激素性股骨頭壞死中對(duì)軟骨細(xì)胞的作用[A];2009第十七屆全國(guó)中西醫(yī)結(jié)合骨傷科學(xué)術(shù)研討會(huì)論文匯編[C];2009年

8 李建華;黃建榮;康奕飛;許繼德;涂永生;;體外誘導(dǎo)人骨髓間充質(zhì)干細(xì)胞分化為軟骨細(xì)胞的研究[A];中南地區(qū)第六屆生理學(xué)學(xué)術(shù)會(huì)議論文摘要匯編[C];2004年

9 石印玉;曹月龍;馮偉;鄭昱新;石瑛;王翔;;補(bǔ)腎、柔肝中藥對(duì)軟骨細(xì)胞生物功能的影響[A];2004'中華中醫(yī)藥科技成果專輯[C];2004年

10 許道榮;金丹;肖庭輝;余斌;;長(zhǎng)時(shí)間拉伸應(yīng)變對(duì)軟骨細(xì)胞生化環(huán)境的影響[A];第20屆中國(guó)康協(xié)肢殘康復(fù)學(xué)術(shù)年會(huì)論文選集[C];2011年

相關(guān)重要報(bào)紙文章 前10條

1 聶翠蓉;英科學(xué)家從成人骨骼中找到軟骨干細(xì)胞[N];科技日?qǐng)?bào);2008年

2 吳一福;西安交大：用人胎兒軟骨細(xì)胞培養(yǎng)成功軟骨組織工程種子細(xì)胞[N];中國(guó)醫(yī)藥報(bào);2006年

3 中文;人體軟骨舉足輕重[N];廣東科技報(bào);2000年

4 劉霞;英用患者組織細(xì)胞成功培育出再生軟骨[N];科技日?qǐng)?bào);2010年

5 保健時(shí)報(bào)特約記者 方序;體外“養(yǎng)”一塊軟骨補(bǔ)膝蓋[N];保健時(shí)報(bào);2011年

6 記者 張可喜;培養(yǎng)軟骨細(xì)胞[N];新華每日電訊;2002年

7 健康時(shí)報(bào)記者 李海清;軟骨破了打“補(bǔ)丁”[N];健康時(shí)報(bào);2009年

8 楊春;藥物增高不可信[N];大眾衛(wèi)生報(bào);2005年

9 黃楓 謝國(guó)平;中醫(yī)藥治療膝骨關(guān)節(jié)炎實(shí)驗(yàn)研究進(jìn)展[N];中國(guó)中醫(yī)藥報(bào);2006年

10 記者 何屹;英國(guó)用干細(xì)胞成功培育出軟骨組織[N];科技日?qǐng)?bào);2005年

相關(guān)博士學(xué)位論文 前10條

1 王曉鳳;自噬在軟骨發(fā)育不全與軟骨生成中的作用與機(jī)制研究[D];第三軍醫(yī)大學(xué);2015年

2 王勝楠;杜仲苷對(duì)IL-1β誘導(dǎo)的軟骨細(xì)胞分解代謝和凋亡的影響及其作用機(jī)制[D];南方醫(yī)科大學(xué);2015年

3 張?jiān)?MiR-145在原發(fā)性膝關(guān)節(jié)骨性關(guān)節(jié)炎軟骨中的表達(dá)及其意義[D];天津醫(yī)科大學(xué);2015年

4 張龍強(qiáng);整合素β1促進(jìn)GIT1表達(dá)而影響軟骨細(xì)胞增殖凋亡的研究[D];山東大學(xué);2015年

5 馬中希;周期性張應(yīng)力對(duì)大鼠生長(zhǎng)板軟骨細(xì)胞的增殖和凋亡作用[D];華中科技大學(xué);2015年

6 劉艷;BMP-2在骨性關(guān)節(jié)炎中表達(dá)的意義及其誘導(dǎo)凋亡及增殖的研究[D];吉林大學(xué);2016年

7 甄允方;軟骨干細(xì)胞來(lái)源的微囊泡對(duì)骨髓間充質(zhì)干細(xì)胞分化、增殖的作用及機(jī)理的研究[D];蘇州大學(xué);2016年

8 鄢博;mTORC1通路調(diào)節(jié)PTHrP來(lái)調(diào)控軟骨生長(zhǎng)、增殖、分化[D];南方醫(yī)科大學(xué);2016年

9 張國(guó)梁;miRNA-502-5p對(duì)骨關(guān)節(jié)炎軟骨細(xì)胞損傷的生物學(xué)作用及機(jī)制研究[D];南方醫(yī)科大學(xué);2016年

10 薛恩興;地塞米松激活自噬對(duì)軟骨細(xì)胞衰老影響的研究[D];南方醫(yī)科大學(xué);2016年

相關(guān)碩士學(xué)位論文 前10條

1 張君;3.0T磁共振對(duì)膝關(guān)節(jié)移植軟骨的形態(tài)學(xué)評(píng)估及T2mapping分層定量評(píng)價(jià)[D];中國(guó)人民解放軍醫(yī)學(xué)院;2015年

2 李亮;骨形成蛋白-7促進(jìn)多孔鉭—軟骨細(xì)胞分泌功能及基因表達(dá)的實(shí)驗(yàn)研究[D];河北聯(lián)合大學(xué);2014年

3 簡(jiǎn)曉蕾;甲狀旁腺激素(1-34)對(duì)豚鼠自發(fā)性O(shè)A模型作用的體內(nèi)體外實(shí)驗(yàn)研究[D];河北聯(lián)合大學(xué);2014年

4 趙陽(yáng);堿性成纖維細(xì)胞生長(zhǎng)因子（bFGF）對(duì)多孔鉭—軟骨細(xì)胞復(fù)合物細(xì)胞增殖及分化影響的實(shí)驗(yàn)研究[D];河北聯(lián)合大學(xué);2014年

5 趙宏坤;精氨酸—甘氨酸—天冬氨酸（RGD）多肽修飾多孔鉭材料對(duì)軟骨細(xì)胞粘附性影響的實(shí)驗(yàn)研究[D];河北聯(lián)合大學(xué);2014年

6 魏麗杰;降鈣素對(duì)IL-1β誘導(dǎo)的大鼠軟骨細(xì)胞炎性反應(yīng)的影響[D];河北聯(lián)合大學(xué);2014年

7 張嶺;國(guó)產(chǎn)多孔鉭對(duì)大鼠軟骨細(xì)胞生物學(xué)行為及功能變化的體外研究[D];河北聯(lián)合大學(xué);2014年

8 史東;uPA-siRNA重組慢病毒載體感染兔軟骨細(xì)胞對(duì)其增殖情況初步研究[D];石河子大學(xué);2015年

9 王林林;體外兔軟骨細(xì)胞的分離，培養(yǎng)與鑒定的研究[D];新鄉(xiāng)醫(yī)學(xué)院;2015年

10 秦洋洋;IGF1R基因沉默對(duì)梅花鹿鹿茸軟骨細(xì)胞增殖周期凋亡等作用研究[D];華中農(nóng)業(yè)大學(xué);2015年

，

本文編號(hào)：2477651