本文選題：發(fā)育性髖關(guān)節(jié)脫位 + 動(dòng)物模型　； 參考：《復(fù)旦大學(xué)》2012年博士論文

【摘要】：[背景和目的] 發(fā)育性髖關(guān)節(jié)脫位(Developmental dislocation of the hip, DDH)是小兒矯形外科最常見(jiàn)的疾病之一,骨關(guān)節(jié)炎(Osteoarthritis, OA)是其最常見(jiàn)的遠(yuǎn)期并發(fā)癥。與正常人相比,DDH骨關(guān)節(jié)炎發(fā)病年齡早且病情重,大多數(shù)必須進(jìn)行全髖關(guān)節(jié)置換術(shù)(Total hip arthroplasty,THA),嚴(yán)重影響了生活質(zhì)量。本課題組前期研究發(fā)現(xiàn)發(fā)育性髖關(guān)節(jié)脫位早期可能已經(jīng)存在關(guān)節(jié)軟骨的退行性改變。目前對(duì)于DDH的早期發(fā)生關(guān)節(jié)軟骨退行性變及骨關(guān)節(jié)炎的分子生物學(xué)機(jī)制尚不明確,近年來(lái)有大量研究表明β-catenin及其所在Wnt信號(hào)通路在關(guān)節(jié)軟骨的形成和退行性改變中起關(guān)鍵作用,但β-catenin在髖關(guān)節(jié)脫位關(guān)節(jié)軟骨的早期退變中有無(wú)作用的研究尚未見(jiàn)報(bào)道。本研究旨在通過(guò)檢測(cè)β-catenin與關(guān)節(jié)軟骨早期退變有關(guān)的膠原、基質(zhì)金屬蛋白酶(MMPs)和解聚素等在DDH早期髖臼軟骨中的表達(dá)的相關(guān)性,探討β-catenin與DDH早期軟骨退行性變化的相關(guān)性,研究DDH早期軟骨退變的機(jī)制,為臨床DDH的早期預(yù)防骨關(guān)節(jié)炎提供理論依據(jù),為進(jìn)一步深入研究DDH與骨性關(guān)節(jié)炎的關(guān)系提供新的思路。 [方法] 一、DDH動(dòng)物模型的制作、病理組織學(xué)觀察 1.根據(jù)襁褓體位好發(fā)髖關(guān)節(jié)脫位,對(duì)新生20只Wistar大鼠雙下肢雙髖雙膝醫(yī)用膠帶并攏模擬襁褓體位固定10天,大體觀察證實(shí)制模成功情況。 2.實(shí)驗(yàn)組大鼠固定10天后解除固定繼續(xù)飼養(yǎng),對(duì)2、4、6、8周DDH模型及對(duì)應(yīng)周期正常發(fā)育大鼠各10只髖關(guān)節(jié)軟骨進(jìn)行大體觀察,測(cè)量髖臼深度、長(zhǎng)度及寬度；股骨頭長(zhǎng)度及寬度。 3.髖關(guān)節(jié)軟骨標(biāo)本Safranin O/Fast green染色后光鏡下觀察關(guān)節(jié)軟骨細(xì)胞與細(xì)胞外基質(zhì)的病理組織學(xué)改變。 二、X型膠原、基質(zhì)金屬蛋白酶-13(MMP-13)、ADAMTS-4、ADAMTS-5、β-catenin在不同時(shí)期DDH髖關(guān)節(jié)軟骨中的表達(dá) 1.第一部分DDH模型不同年齡和對(duì)應(yīng)期對(duì)照鼠各10只髖關(guān)節(jié)軟骨標(biāo)本。 2.采用免疫組化染色檢測(cè)X型膠原、MMP-13、β-catenin在不同年齡髖關(guān)節(jié)軟骨中表達(dá)的改變。 3.采用qRT-PCR法檢測(cè)X型膠原、MMP-13、ADAMTS-4、ADAMTS-5、β-catenin 在不同年齡髖關(guān)節(jié)軟骨中表達(dá)的改變,SPSS16.0統(tǒng)計(jì)和比較組間差異。三、體外軟骨細(xì)胞培養(yǎng),激活β-catenin的表達(dá),檢測(cè)β-catenin對(duì)軟骨細(xì)胞 退行性改變的影響 1.8周對(duì)照組大鼠髖關(guān)節(jié)軟骨細(xì)胞的提取及原代培養(yǎng),Ⅱ型膠原免疫熒光及甲苯胺藍(lán)染色鑒定,免疫熒光及qRT-PCR檢測(cè)MMP13及X型膠原的表達(dá),qRT-PCR檢測(cè)ADAMTS-5的表達(dá),TUNEL法檢測(cè)軟骨細(xì)胞凋亡。 2.LiCl處理正常發(fā)育8周鼠關(guān)節(jié)軟骨細(xì)胞,激活β-catenin的表達(dá),qRT-PCR檢測(cè)X型膠原、MMP-13和ADAMTS-5的表達(dá)；檢測(cè)軟骨細(xì)胞凋亡情況。 3. SPSS16.0統(tǒng)計(jì)和比較組間差異。 [結(jié)果] 一、DDH動(dòng)物模型的制作及病理組織學(xué)觀察 1.建模成功率100%(20只新生大鼠固定10天)。 2.髖關(guān)節(jié)大體觀察：實(shí)驗(yàn)組關(guān)節(jié)囊增厚,髖臼淺平,軟組織嵌入,股骨頭外形扁平,隨年齡增長(zhǎng)頭臼匹配差距增大；測(cè)量結(jié)果顯示2、4周大鼠髖臼及股骨頭大小較對(duì)照組發(fā)育小,但仍呈發(fā)育增大趨勢(shì),6周后髖臼發(fā)育基本停止,髖臼大小開(kāi)始變小,股骨頭發(fā)育停止,頭臼不對(duì)稱(chēng)進(jìn)一步加重(P0.01)。 3. Safranin0/Fast green染色可見(jiàn)到實(shí)驗(yàn)組關(guān)節(jié)軟骨退變征象：Safranin0染色淺層部分染色降低,表明帶負(fù)電荷蛋白多糖明顯降低、4周后關(guān)節(jié)軟骨淺層裂隙形成、淺層中層軟骨細(xì)胞簇聚及數(shù)量減少、關(guān)節(jié)軟骨退變隨鼠齡增長(zhǎng)而加重。 二、X型膠原、基質(zhì)金屬蛋白酶-13(MMP-13)、ADAMTS-4、ADAMTS-5、B-catenin在不同時(shí)期DDH髖關(guān)節(jié)軟骨中的表達(dá) 1.實(shí)驗(yàn)組X型膠原、MMP-13在軟骨層軟骨細(xì)胞中不均勻表達(dá),成簇細(xì)胞表達(dá)明顯,胞漿內(nèi)明顯棕色深染細(xì)胞數(shù)目百分比較對(duì)照組多。4周及以后與對(duì)照組比較差異有統(tǒng)計(jì)學(xué)意義(P0.01),且隨鼠齡增長(zhǎng)而表達(dá)增高。 2.實(shí)時(shí)熒光定量PCR結(jié)果顯示實(shí)驗(yàn)組X型膠原和MMP-13mRNA在4周及以后表達(dá)較對(duì)照組增加,且隨鼠齡增長(zhǎng)表達(dá)增加；ADAMTS-5在8周時(shí)表達(dá)增高,與對(duì)照組比較差異有統(tǒng)計(jì)學(xué)意義(P0.01)。ADAMTS-4與實(shí)驗(yàn)組比較無(wú)統(tǒng)計(jì)學(xué)差異。 3. β-catenin:免疫組織化學(xué)中可見(jiàn)β-catenin在對(duì)照組大鼠2周時(shí)表達(dá)較多,隨鼠齡增長(zhǎng)表達(dá)逐漸下降,8周時(shí)免疫組化基本無(wú)表達(dá)；實(shí)驗(yàn)組β-catenin表達(dá)無(wú)下降趨勢(shì),持續(xù)高表達(dá)；實(shí)時(shí)熒光定量PCR mRNA表達(dá)呈相似結(jié)果。 三、體外軟骨細(xì)胞培養(yǎng),檢測(cè)β-catenin對(duì)軟骨細(xì)胞退行性改變的影響 1.軟骨細(xì)胞培養(yǎng)及鑒定：軟骨細(xì)胞培養(yǎng)后Ⅱ型膠原免疫熒光及甲苯胺藍(lán)染色鑒定為軟骨細(xì)胞。 2. LiCl激活β-catenin表達(dá)：LiCl處理8周正常軟骨細(xì)胞后免疫熒光及qRT-PCR均提示β-catenin表達(dá)明顯增高。 3.激活β-catenin引起軟骨退行性改變：LiCl處理軟骨細(xì)胞免疫熒光提示X型膠原及MMP-13表達(dá)增高明顯；qRT-PCR提示X型膠原、MMP-13、ADAMTS-5表達(dá)增高(P0.01);TUNEL染色提示LiCl處理后軟骨細(xì)胞凋亡明顯增加(P0.01)。 [結(jié)論] 1.DDH動(dòng)物模型早期關(guān)節(jié)軟骨發(fā)育落后并在4周出現(xiàn)發(fā)育停滯退變、軟骨蛋白多糖丟失等關(guān)節(jié)軟骨退變,這種早期發(fā)育異常及軟骨退變可能是DDH最終發(fā)生骨關(guān)節(jié)炎的病理學(xué)基礎(chǔ)。 2.與關(guān)節(jié)軟骨退變有關(guān)的X型膠原、MMP-13及ADAMTS-5在DDH早期就表達(dá)增多,可以作為反映DDH軟骨退變的早期敏感生物學(xué)指標(biāo)。 3.β-catenin在正常發(fā)育早期有促進(jìn)關(guān)節(jié)軟骨發(fā)育的作用,但成熟后不再表達(dá),而在DDH整個(gè)發(fā)育過(guò)程中,關(guān)節(jié)軟骨出現(xiàn)持續(xù)高表達(dá)提示其可能是參與了軟骨退行性變。 4.關(guān)節(jié)軟骨發(fā)育異常導(dǎo)致β-catenin在DDH動(dòng)物模型早期持續(xù)高表達(dá),并可能引起X型膠原、MMP-13及ADAMTS-5等合成增多,軟骨細(xì)胞凋亡增加,由此導(dǎo)致關(guān)節(jié)軟骨早期退行性改變,這可能是DDH最終導(dǎo)致骨關(guān)節(jié)炎發(fā)生的機(jī)制之一
[Abstract]:[background and purpose]
Developmental dislocation of the hip (Developmental dislocation of the hip, DDH) is one of the most common diseases in pediatric orthopedics. Osteoarthritis (Osteoarthritis, OA) is the most common long-term complication. Compared with normal people, DDH osteoarthritis is early and is seriously ill, and most of them must be replaced by total hip arthroplasty (Total hip Arthr). Oplasty, THA), seriously affected the quality of life. Earlier studies in our group have found that there may have been degenerative changes in articular cartilage in the early stage of developmental dislocation of the hip. The molecular biological mechanism of osteoarthritis in the early stages of DDH is not clear. In recent years, a large number of studies have shown that beta -catenin and The Wnt signaling pathway plays a key role in the formation and degenerative changes of articular cartilage, but the study of the role of beta -catenin in the early degeneration of articular cartilage in the hip joint dislocation has not been reported. The aim of this study was to detect collagen, matrix metalloproteinase (MMPs) and depolymerization of beta -catenin and the early degeneration of articular cartilage. The correlation between the expression of element in the early acetabular cartilage of DDH and the correlation between the early chondrodegenerative changes of beta -catenin and DDH and the study of the mechanism of early cartilage degeneration in DDH provide a theoretical basis for the early prevention of osteoarthritis of the clinical DDH, and provide a new idea for further in-depth study of the relationship between DDH and osteoarthritis.
[method]
The production of DDH animal model, histopathological observation
1. according to the dislocation of the hip joint in the infancy, the new 20 Wistar rats with double hips and double knees and double knees and double knees were closed for 10 days, and the success of the model was confirmed by the general observation.
2. the rats in the experimental group were reared for 10 days after fixation. The 2,4,6,8 week DDH model and the 10 hip articular cartilage of the normal developing rats were observed, and the depth, length and width of the acetabulum were measured, and the length and width of the femoral head were measured.
3. histopathological changes of articular cartilage cells and extracellular matrix were observed by Safranin O/Fast green staining.
Two, the expression of type X collagen, matrix metalloproteinase -13 (MMP-13), ADAMTS-4, ADAMTS-5, and beta -catenin at different stages of DDH hip cartilage.
1. part I DDH model of 10 different age and corresponding control rats.
2. immunohistochemical staining was used to detect the expression of type X collagen, MMP-13 and beta -catenin in hip cartilage at different ages.
3. X collagen, MMP-13, ADAMTS-4, ADAMTS-5 and beta -catenin were detected by qRT-PCR.
Changes in cartilage expression in hip articular cartilage of different ages, SPSS16.0 statistics and comparison between groups. Three, in vitro chondrocyte culture, activation of the expression of beta -catenin, and detection of chondrocytes by beta -catenin
Effects of degenerative changes
The chondrocytes of the hip joint in the 1.8 week control group were extracted and cultured, the collagen type II was identified by immunofluorescence and toluidine blue, the expression of MMP13 and X collagen was detected by immunofluorescence and qRT-PCR, the expression of ADAMTS-5 was detected by qRT-PCR, and the apoptosis of cartilage cells was detected by TUNEL.
2.LiCl treated normal development of chondrocytes in 8 weeks and activated the expression of beta -catenin. QRT-PCR was used to detect the expression of X type collagen, MMP-13 and ADAMTS-5, and the apoptosis of cartilage cells was detected.
3. SPSS16.0 statistics and comparison between groups.
[results]
One, DDH animal model making and histopathological observation.
1. the success rate of modeling was 100% (20 newborn rats were fixed for 10 days).
2. hip joint gross observation: the joint capsule in the experimental group was thickened, the acetabulum was shallow, the soft tissue was embedded, the shape of the femoral head was flat, and the gap between the head of the head of the femoral head increased with age. The measurement results showed that the size of the acetabulum and the femoral head in 2,4 week rats was smaller than the control group, but the growth trend was still growing, the development of acetabulum was basically stopped after 6 weeks and the size of acetabulum began to begin. The development of femoral head was stopped and the asymmetry of the head and socket was further aggravated (P0.01).
3. Safranin0/Fast green staining showed the signs of articular cartilage degeneration in the experimental group: the superficial staining decreased in the superficial layer of Safranin0 staining, indicating that the negative charged protein polysaccharide was obviously reduced, the shallow fracture of the articular cartilage was formed after 4 weeks, the cartilage cells in the shallow layer were clustered and the number decreased, and the degeneration of articular cartilage was aggravated with the age of rat.
Two, the expression of type X collagen, matrix metalloproteinase -13 (MMP-13), ADAMTS-4, ADAMTS-5 and B-catenin in DDH hip cartilage at different stages.
1. the type X collagen in the experimental group was unevenly expressed in the chondrocytes of the chondrocytes, and the expression of the cluster cells was obvious. The number of brown deep stained cells in the cytoplasm was more than that of the control group for more than.4 weeks and after the control group, the difference was statistically significant (P0.01), and the expression increased with the growth of the rat age.
2. real time fluorescence quantitative PCR results showed that the expression of type X collagen and MMP-13mRNA in the experimental group was increased in 4 weeks and after the control group, and the expression increased with the age of rat. The expression of ADAMTS-5 increased at 8 weeks. There was a significant difference between the control group and the control group (P0.01).ADAMTS-4 and the experimental group.
3. beta -catenin: immunohistochemical staining showed that the expression of beta -catenin was more in the control group at 2 weeks, and gradually decreased with the growth of rat age. The expression of immuno histochemistry was basically no expression at 8 weeks, and the expression of beta -catenin in the experimental group had no downward trend and continued high expression, and the real-time fluorescence quantitative PCR mRNA table showed similar results.
Three, in vitro chondrocyte culture, to detect the effect of beta -catenin on the degeneration of chondrocytes.
1. chondrocyte culture and identification: chondrocytes cultured after type II collagen immunofluorescence and toluidine blue staining were identified as chondrocytes.
2. LiCl activated the expression of beta -catenin: immunofluorescence and qRT-PCR showed that the expression of beta -catenin increased significantly after LiCl treatment for 8 weeks in normal chondrocytes.
3. activation of beta -catenin induced degeneration of cartilage: LiCl treated chondrocyte immunofluorescence suggested that the expression of type X collagen and MMP-13 increased obviously; qRT-PCR suggested X collagen, MMP-13, ADAMTS-5 expression increased (P0.01); TUNEL staining suggested that apoptotic chondrocyte apoptosis was significantly increased after LiCl treatment (P0.01).
[Conclusion]
The early development of articular cartilage in the 1.DDH animal model is backward and the development of stagnation and degeneration, cartilage protein polysaccharide loss and other articular cartilage degeneration appear at 4 weeks. This early dysplasia and cartilage degeneration may be the pathological basis of osteoarthritis of DDH.
2. the expression of type X collagen, MMP-13 and ADAMTS-5 related to articular cartilage degeneration is increased in the early stage of DDH, which can be used as an early sensitive biological indicator to reflect the degeneration of DDH cartilage.
3. beta -catenin can promote articular cartilage development at the early stage of normal development, but no longer expression after maturation, and the continuous high expression of articular cartilage in the whole development of DDH suggests that it may be involved in degeneration of cartilage.
4. articular cartilage abnormal development leads to the high expression of beta -catenin in early DDH animal model, and may cause X collagen, MMP-13 and ADAMTS-5 synthesis increase, cartilage cell apoptosis increase, resulting in the early degeneration of articular cartilage, which may be one of the mechanisms that DDH eventually leads to the occurrence of osteoarthrosis.
【學(xué)位授予單位】：復(fù)旦大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2012
【分類(lèi)號(hào)】：R726.8

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2 王超華;朱梅;張子博;劉軍;任凱晶;盧飚;李鳳翱;邱明才;;Wnt/beta-catenin信號(hào)通路與骨關(guān)節(jié)炎發(fā)病機(jī)制的實(shí)驗(yàn)研究[A];中華醫(yī)學(xué)會(huì)第三次骨質(zhì)疏松和骨礦鹽疾病中青年學(xué)術(shù)會(huì)議論文匯編[C];2011年

3 邊紅光;潘浩;李雄峰;;補(bǔ)腎壯筋湯對(duì)兔早期膝骨關(guān)節(jié)炎關(guān)節(jié)軟骨病理改變的影響[A];浙江省中西醫(yī)結(jié)合學(xué)會(huì)骨傷科專(zhuān)業(yè)委員會(huì)第十二次學(xué)術(shù)年會(huì)、杭州市中醫(yī)藥協(xié)會(huì)骨傷科專(zhuān)業(yè)委員會(huì)第一次學(xué)術(shù)年會(huì)暨繼續(xù)教育學(xué)習(xí)班論文匯編[C];2006年

4 張春秋;秦曉峰;董心;武漢;葉金鐸;劉海英;;滾壓與壓縮力學(xué)條件下關(guān)節(jié)軟骨工程化構(gòu)建力學(xué)狀態(tài)的仿真研究[A];2008年全國(guó)生物流變學(xué)與生物力學(xué)學(xué)術(shù)會(huì)議論文摘要集[C];2008年

5 蔡建平;胡鋼;;淺析透明質(zhì)酸鈉結(jié)合其它方法治療膝骨性關(guān)節(jié)炎[A];中華中醫(yī)藥學(xué)會(huì)骨傷分會(huì)第四屆第二次會(huì)議論文匯編[C];2007年

6 呂愛(ài)平;徐世杰;劉振麗;王安民;;關(guān)節(jié)免疫損傷動(dòng)物模型——Ⅱ型膠原所致關(guān)節(jié)炎研究進(jìn)展[A];中國(guó)中醫(yī)研究院基礎(chǔ)理論研究所學(xué)術(shù)論文匯編[C];1997年

7 王德杭;;軟骨的磁共振定量定性研究[A];中國(guó)醫(yī)師協(xié)會(huì)放射醫(yī)師分會(huì)首屆會(huì)員大會(huì)暨第四屆醫(yī)學(xué)影像山東論壇、山東省第16次放射學(xué)會(huì)議暨山東省第14屆醫(yī)學(xué)影像學(xué)學(xué)術(shù)研討會(huì)論文集[C];2007年

8 杜寧;陸勇;顧翔;胡炯;;手法促進(jìn)膝關(guān)節(jié)炎軟骨修復(fù)的核磁共振病例對(duì)照研究[A];第十六屆全國(guó)中西醫(yī)結(jié)合骨傷科學(xué)術(shù)研討會(huì)暨中西醫(yī)結(jié)合手法治療骨傷科疾病新進(jìn)展學(xué)習(xí)班論文匯編[C];2008年

9 王超華;朱梅;張子博;劉軍;任凱晶;盧飚;李鳳翱;邱明才;;Wnt/β-catenin信號(hào)通路與骨關(guān)節(jié)炎發(fā)病機(jī)制的實(shí)驗(yàn)研究[A];中華醫(yī)學(xué)會(huì)第十次全國(guó)內(nèi)分泌學(xué)學(xué)術(shù)會(huì)議論文匯編[C];2011年

10 劉志翔;張柳;張楠;;降鈣素對(duì)兔骨關(guān)節(jié)炎軟骨基質(zhì)金屬蛋白酶的影響[A];全國(guó)骨科臨床研究新進(jìn)展研討會(huì)暨學(xué)習(xí)班論文集[C];2006年

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2 何杰;防治骨刺有招數(shù)[N];保健時(shí)報(bào);2006年

3 黃遂柱;半月板損傷 關(guān)節(jié)軟骨“遭殃”[N];家庭醫(yī)生報(bào);2006年

4 健康時(shí)報(bào)記者 常賓 特約記者 郭樝;70歲不摔跤 80歲不彎腰[N];健康時(shí)報(bào);2010年

5 北京朝陽(yáng)醫(yī)院（京西院區(qū)）骨科 楊立輝;骨關(guān)節(jié)炎治療誤區(qū)多[N];保健時(shí)報(bào);2006年

6 中國(guó)人民解放軍總醫(yī)院骨科教授 王巖 上海市藥品不良反應(yīng)監(jiān)測(cè)中心常務(wù)副主任 杜文民 徐洪志 北京大學(xué)醫(yī)院部教授 王孝道 武漢市第一醫(yī)院中醫(yī)部風(fēng)濕科 潘靜;骨性關(guān)節(jié)炎的防治[N];中國(guó)老年報(bào);2004年

7 遠(yuǎn)威 婁曉芬 上海瑞金醫(yī)院骨科主任、教授 中華醫(yī)學(xué)會(huì)骨科學(xué)分會(huì)副主任委員 楊慶銘 北京積水潭醫(yī)院骨科主任醫(yī)師 李為 北京大學(xué)第三醫(yī)院骨科主任醫(yī)師、教授 婁思權(quán) 呂婷婷;世衛(wèi)組織啟動(dòng)骨與關(guān)節(jié)10年計(jì)劃[N];中國(guó)老年報(bào);2004年

8 陳祖亮;我組織工程研究獲重大突破[N];上海科技報(bào);2000年

9 梁海清;關(guān)節(jié)痛患者究竟該如何運(yùn)動(dòng)[N];中國(guó)老年報(bào);2008年

10 王學(xué)東;骨關(guān)節(jié)炎患者如何鍛煉[N];中國(guó)中醫(yī)藥報(bào);2007年

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1 寧波;β-catenin在發(fā)育性髖關(guān)節(jié)脫位動(dòng)物模型早期軟骨退行性變中機(jī)制的實(shí)驗(yàn)研究[D];復(fù)旦大學(xué);2012年

2 周強(qiáng);異體軟骨細(xì)胞復(fù)合透明質(zhì)酸芐基酯凝膠修復(fù)關(guān)節(jié)軟骨缺損[D];中國(guó)醫(yī)科大學(xué);2005年

3 段王平;不同年齡兔膝關(guān)節(jié)軟骨單位生物學(xué)特性分析[D];山西醫(yī)科大學(xué);2011年

4 牛維;補(bǔ)腎活血方治療絕經(jīng)后骨關(guān)節(jié)炎的實(shí)驗(yàn)研究[D];廣州中醫(yī)藥大學(xué);2005年

5 余方圓;幾種構(gòu)建組織工程關(guān)節(jié)軟骨方法的比較研究[D];中國(guó)人民解放軍軍醫(yī)進(jìn)修學(xué)院;2004年

6 夏軍;兔骨關(guān)節(jié)炎軟骨中MMPs以及MAPKs信號(hào)通路激酶表達(dá)調(diào)控的初步研究[D];復(fù)旦大學(xué);2008年

7 關(guān)雪峰;人類(lèi)原發(fā)性膝關(guān)節(jié)骨性關(guān)節(jié)炎病變軟骨全基因組表達(dá)與分析[D];遼寧中醫(yī)藥大學(xué);2009年

8 吳林蘭;中醫(yī)手法對(duì)退行性骨關(guān)節(jié)炎作用效應(yīng)及其機(jī)理研究[D];湖北中醫(yī)學(xué)院;2007年

9 郭全義;自體軟骨細(xì)胞—藻酸鈣復(fù)合物修復(fù)羊膝關(guān)節(jié)負(fù)重區(qū)全層軟骨缺損的實(shí)驗(yàn)研究[D];中國(guó)人民解放軍軍醫(yī)進(jìn)修學(xué)院;2006年

10 吳銀松;辛伐他汀對(duì)骨關(guān)節(jié)炎軟骨保護(hù)作用的實(shí)驗(yàn)研究[D];第四軍醫(yī)大學(xué);2007年

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1 張迪;δ-catenin和small GTP酶的協(xié)同表達(dá)與肺癌的惡性程度相關(guān)[D];中國(guó)醫(yī)科大學(xué);2010年

2 楊健;Wnt-1及β-catenin在大腸側(cè)向發(fā)育型腫瘤組織中的表達(dá)及意義[D];大連醫(yī)科大學(xué);2010年

3 張?jiān)茟c;Wnt2及β-catenin蛋白在食道癌中的表達(dá)特點(diǎn)及意義[D];大連醫(yī)科大學(xué);2010年

4 李志強(qiáng);肝癌細(xì)胞中β-catenin調(diào)控下游靶基因CCN1/Cyr61的研究[D];第三軍醫(yī)大學(xué);2010年

5 張建國(guó);Cripto-1和β-catenin蛋白表達(dá)與胃癌發(fā)生和轉(zhuǎn)移的關(guān)系及意義[D];中國(guó)醫(yī)科大學(xué);2010年

6 牛歡;堿性成纖維細(xì)胞生長(zhǎng)因子調(diào)節(jié)大鼠心臟成纖維細(xì)胞β-catenin的表達(dá)[D];蘭州大學(xué);2010年

7 陳楊榮;肝細(xì)胞癌中β-catenin和APC蛋白的表達(dá)及其意義研究[D];浙江大學(xué);2010年

8 王西;β-catenin與MMP-7在子宮內(nèi)膜異位癥中的表達(dá)及意義[D];中南大學(xué);2010年

9 王林娜;RUNX3和β-catenin在散發(fā)性結(jié)直腸管狀腺瘤癌變過(guò)程中的表達(dá)及作用[D];河北醫(yī)科大學(xué);2011年

10 滕穎;Wnt/β-catenin信號(hào)通路對(duì)肺腺癌A549細(xì)胞腫瘤干細(xì)胞特性作用研究[D];山東大學(xué);2010年

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