不同冷冻方法保存同种异体关节软骨移植后的生物学活性特征

目的：观察经梯度降温、冷冻保存的同种异体关节软骨移植后的生物学活性，为临床治疗大面积关节软骨缺损提供依据。方法：实验组将经梯度降温、冷冻保存的兔膝关节半髁异体移植。同时设对照组。分别于术后8，12，24周进行关节软骨大体形态及组织学观察。结果：8周时移植关节软骨形态正常成活，软骨细胞排列尚整齐，12周时移植关节软骨恢复正常透明软骨形态，修复组织与周围融合。24周时部分关节软骨表面有退行性变，与周围关节软骨愈合良好。结论：经梯度降温、冷冻保存的同种关节软骨移植可作为修复大面积关节软骨缺损的一种治疗方法。     

不同冷冻方法保存同种异体关节软骨移植后的生物学活性特征

目的:观察经梯度降温、冷冻保存的同种异体关节软骨移植后的生物学活性,为临床治疗大面积关节软骨缺损提供依据。方法:实验组将经梯度降温、冷冻保存的兔膝关节半髁异体移植。同时设对照组。分别于术后8,12,24周进行关节软骨大体形态及组织学观察。结果:8周时移植关节软骨形态正常成活,软骨细胞排列尚整齐,12周时移植关节软骨恢复正常透明软骨形态,修复组织与周围融合。24周时部分关节软骨表面有退行性变,与周围关节软骨愈合良好。结论:经梯度降温、冷冻保存的同种关节软骨移植可作为修复大面积关节软骨缺损的一种治疗方法。     

应用组织工程学技术修复关节软骨缺损

目的：关节软骨缺损一直是临床上的一个难题。目前的治疗包括自体或异体骨软骨移植修复、软骨膜或骨膜移植修复、组织工程学技术的发展使体外培养软骨细胞修复关节软骨缺损进入了一个新的发展时期，通过查阅文献对体外培养软骨细胞修复关节软骨缺损进行综述。资料来源：应用汁算机检索Medline 1993-01／2004-06关于组织工程学技术修复关节软骨缺损的文章，检索词为“articular cartilage defects、tissue engineering technology”，限定语言种类为英文；同时计算机检索中国期刊数据库1993-01／2004-06相关组织工程学技术修复关节软骨缺损的文章，检索词“关节软骨缺损，组织工程学技术，体外培养”，限定语言种类为中文资料选择：对资料进行初审，纳入标准：小有关软骨细胞的结构、功能、及其体外培养的意义研究：②有关体外培养种子细胞的选择的研究：⑧软骨细胞修复关常软骨缺损的前景展望的研究。排除标准：文献中重复研究、综述、Mata分析类文章：未排除文章中资料是否应用了随机、对照和盲法。资料提炼：共收集到32篇相关文献，含追溯法查找文献6篇，18篇符合纳入标准，排除14篇文献，其中4篇系重复研究，7篇为临床应用，3篇为软骨细胞支架的研究。18篇文献中有7篇对软骨细胞的特征进行综述，5篇是理想种子细胞的选择的研究，6篇为软骨细胞修复关节软骨缺损的前景展望的研究一资料综合：软骨细胞体外培养大量扩增、分化维持其正常的表型及代谢的调控因素为组织工程化软骨修复软骨缺损、体外培养软骨细胞建立软骨细胞库开拓了一条新的途径：软骨细胞，间充质干细胞（骨髓、骨膜或软骨膜来源）、滑膜细胞或转基因细胞等均町作为种子细胞。可来源于同种异体甚至异种细胞。自体软骨细胞植入技术已经作为一个传统自体软骨细胞移植术的替代品被骨科界广泛接受：结论：体外培养软骨细胞技术，目前已经成熟。组织工程学技术修复关节软骨缺损的方法很多：组织工程学技术的发展使体外培养转骨细胞修复关节软骨缺损进入了一个新的发展时期，基质诱导的自体软骨细胞植入技术修复关节软骨缺损开辟了新的道路。     

微骨折技术与骨软骨移植治疗关节软骨缺损*

背景：关节镜下微骨折治疗与骨软骨移植是关节软骨缺损主要的治疗方法之一,具有广阔的应用前景。目的：探讨关节镜下微骨折治疗与自体和同种异体骨软骨移植治疗膝骨关节炎合并关节软骨缺损的效果。方法：应用关节镜下微骨折治疗清理术结合软骨缺损区微骨折术治疗膝骨关节炎的临床疗效、临床症状及Tegner 运动评级判定疗效并随访观察3-24个月。自体骨软骨移植治疗关节软骨缺损的患者进行观察随访,通过评价移植后关节活动度、临床症状的改善、关节影像学检查等评估自体骨软骨移植治疗的效果。并对同种异体骨软骨移植治疗关节软骨缺损进行动物实验研究,通过对移植部位的大体观察、组织学观察以及免疫组织化学染色观察,评估同种异体骨软骨移植治疗的效果。结果与结论：关节软骨缺损应用关节镜下微骨折治疗后的患者,关节清理术结合软骨缺损区微骨折术总有效率89.7%。关节软骨缺损应用自体骨软骨移植治疗后的患者,关节疼痛、肿胀的症状改善,关节活动度正常,偶有关节静息痛或活动后轻微疼痛,影像学检查见移植骨软骨位置良好,修复愈合良好。关节软骨缺损应用同种异体骨软骨移植治疗后的实验动物,关节活动度正常,移植关节面光整,关节软骨被透明软骨覆盖,细胞有序排列,软骨基质分泌,修复软骨Ⅱ型胶原免疫组织化学染色强阳性。     

同种异体骨软骨柱移植治疗关节软骨缺损

背景:同种异体骨软骨移植修复关节软骨损伤可以解决自体骨软骨来源有限的问题,但存在免疫排斥问题.目的:观察以深低温保护剂保护的同种异体骨软骨柱移植修复兔关节软骨缺损的效果,并与自体关节软骨移植作比较.设计、时间及地点:随机对照动物实验,于2008 05/10在武汉协和医院骨科实验室完成.材料:24只成年健康新西兰兔中8只用于异体骨软骨柱的制备,16只随机分成同种异体移植组和自体移植组,每组8只.方法:使用横穿钉套筒提取兔股骨内侧髁骨软骨柱,将骨软骨柱在4℃条件下放入盛有10%二甲基亚砜的冻存管中2 h,将冻存管移入程序冷冻仪内以1℃/min速率降至-75℃,放入-196℃液氮罐底部保存3周备用.用横穿钉钻头在兔左膝关节股骨内侧髁垂直于软骨面制造缺损,缺损深4 mm,直径4.45 mm,自体移植组取右膝关节内侧髁骨软骨柱植入到左侧膝关节相应缺损处,异体移植组将经过程序性深低温冷冻保存的同种异体骨软骨柱移植到相应缺损处.主要观察指标:术后12周观察兔关节活动度、修复组织的质地等情况.以苏木精-伊红染色观察关节软骨组织的病理变化,以半定量改良Wakitani score法进行评估.以免疫组织化学染色观察Ⅱ型胶原分泌情况.结果:两组实验动物关节活动度正常.异体移植组移植处关节软骨面较光整,与周围正常关节软骨高度一致,结合紧密,颜色接近,与自体移植组相似.两组移植后,兔关节缺损处被透明软骨覆盖,潮线整齐,细胞排列有序,分泌大量基质,异体移植组移植处软骨深层及软骨下骨处可见微小裂隙,未见淋巴细胞和浆细胞浸润.同种自体与异体骨软骨移植组Wakitaniscore评分结果无统计学差异,总分接近,修复软骨Ⅱ型胶原免疫组织化学染色均强阳性.结论:冷冻同种异体骨软骨柱移植可修复全层小面积关节软骨缺损,术后近期软骨细胞存活,可分泌软骨基质,未见明显排斥反应,与自体骨软骨柱修复的兔关节软骨缺损在组织学上相近.     

应用组织工程学技术修复关节软骨缺损

目的:关节软骨缺损一直是临床上的一个难题。目前的治疗包括自体或异体骨软骨移植修复、软骨膜或骨膜移植修复。组织工程学技术的发展使体外培养软骨细胞修复关节软骨缺损进入了一个新的发展时期,通过查阅文献对体外培养软骨细胞修复关节软骨缺损进行综述。资料来源:应用计算机检索Medline1993-01/2004-06关于组织工程学技术修复关节软骨缺损的文章,检索词为“articularcartilagedefects、tis-sueengineeringtechnology”,限定语言种类为英文;同时计算机检索中国期刊数据库1993-01/2004-06相关组织工程学技术修复关节软骨缺损的文章,检索词“关节软骨缺损,组织工程学技术,体外培养”,限定语言种类为中文。资料选择:对资料进行初审,纳入标准:①有关软骨细胞的结构、功能、及其体外培养的意义研究。②有关体外培养种子细胞的选择的研究。③软骨细胞修复关节软骨缺损的前景展望的研究。排除标准:文献中重复研究、综述、Mata分析类文章。未排除文章中资料是否应用了随机、对照和盲法。资料提炼:共收集到32篇相关文献,含追溯法查找文献6篇,18篇符合纳入标准,排除14篇文献,其中4篇系重复研究,7篇为临床应用,3篇为软骨细胞支架的研究。18篇文献中有7篇对软骨细胞的特征进行综述,5篇是理想种子细胞的选择的研究,6篇为软骨细胞修复关节软骨缺损的前景展望的研究。资料综合:软骨细胞体外培养大量扩增、分化维持其正常的表型及代谢的调控因素为组织工程化软骨修复软骨缺损、体外培养软骨细胞建立软骨细胞库开拓了一条新的途径。软骨细胞、间充质干细胞(骨髓、骨膜或软骨膜来源)、滑膜细胞或转基因细胞等均可作为种子细胞。可来源于同种异体甚至异种细胞。自体软骨细胞植入技术已经作为一个传统自体软骨细胞移植术的替代品被骨科界广泛接受。结论:体外培养软骨细胞技术,目前已经成熟。组织工程学技术修复关节软骨缺损的方法很多。组织工程学技术的发展使体外培养软骨细胞修复关节软骨缺损进入了一个新的发展时期,基质诱导的自体软骨细胞植入技术修复关节软骨缺损开辟了新的道路。     

组织工程化软骨细胞和骨髓间充质干细胞用于修复同种异体关节软骨缺损

背景:关节软骨几乎没有自身修复的能力,目前临床大多采用自体或异体软骨移植修复、软骨膜或骨膜移植修复、软骨细胞移植修复。由于自体软骨来源有限,异体软骨又存在慢性免疫排斥反应,最终可能导致预后不佳;软骨膜或骨膜移植修复的软骨易于退化,导致修复效果不佳。目的:总结组织工程化软骨细胞、骨髓间充质干细胞及两者共培养对同种异体软骨缺损修复作用的研究现状。方法:应用计算机检索PubMed数据库及中国期刊网全文数据库1994-01/2012-01有关组织工程化软骨细胞和骨髓间充质干细胞用于修复同种异体关节软骨缺损方面的文章,英文检索词为"cartilage defect,allograft,chondrocyte,mesenchymal stem cells,bone marrow mesenchymal stem cells",中文检索词为"软骨缺损,同种异体移植,软骨细胞,骨髓间充质干细胞"。排除重复性及非中英文语种研究,共保留35篇文献进行综述。结果与结论:随着体外细胞培养方法的不断改进,现已能够把软骨细胞从坚韧的软骨中分离出来,并获得大量高纯度的软骨细胞并繁殖出新生软骨细胞。软骨细胞培养增殖能力低,传代培养容易引起老化和去分化;而成体骨髓中骨髓间充质干细胞含量少,随传代次数的增多成软骨潜能明显降低。骨髓间充质干细胞和软骨细胞共培养,两种细胞相互促进增殖和分化,作为种子细胞可减少软骨细胞增殖传代次数并节省软骨细胞数量,与组织工程支架材料复合能有效修复关节软骨缺损。     

关节软骨的损伤与修复

关节软骨损伤在临床上很常见，主要由外伤或疾病造成。关节软骨损伤后，自身修复能力很差，长期以来治疗方法很多，疗效多不令人满意。关节软骨损伤修复一直是骨科界关注的难点和重点之一。介绍关节软骨损伤修复的多种方法及其进展，主要包括：软骨下骨钻孔技术、截骨术、骨膜移植技术、软骨细胞或间充质干细胞移植技术、生长因子和人工基质的应用以及自体或同种异体关节软骨的移植技术，并就其临床应用作以说明。     

同种异体骨软骨移植修复关节软骨缺损的实验与应用

目的：关节软骨多处于人体骨骼的重要功能部位，在临床上由于各种原因所导致的关市软骨缺损或变性坏死很常见。日前，使损伤的骨软骨修复至正常骨软骨，许多学者进行了有益的探索：将国内外同种异体骨软骨移植的研究和应用进展，从关节软骨的基础研究、同种异体骨软骨移植的发展概况、取材制备、保存、免疫原性、临床应用等方面做以分析。资料来源：应用计算机检索Medline1980—01／2004—05关于同种异体骨软骨移植的文章，检索词为“Osteochondral allograft”，限定文章语言种类为“English”：同时计算机检索CNK1 1994-01／2004—05关于异体骨软骨移植的文章，检索词为“骨软骨，移植，软骨缺损”，限定文章语言种类为中文。资料选择：对资料进行初审，纳入标准：①有关骨软骨保存方法的实验研究。②有关同种异体骨软骨移植的基础及临床研究。排除标准：文献中重复研究。未排除非随机、对照、盲法文章。资料提炼：共收集到59篇相关文献，追朔法查找文献12篇，29篇符合纳入标准，排除30篇文献，其中8篇重复研究，22篇为异体骨软骨移植在口腔颌面部整容中的应用。资料综合：29篇文章中6篇通过实验方法进行异体骨软骨保存方法的比较研究。10篇通过动物实验或临床研究，以对照研究方法证实同种异体骨软骨移植修复关节软骨缺损的可行性，与自体骨软骨移植相比较的优越性。13篇通过基础或临床研究，证实软骨自身修复能力有限，异体骨软骨移植后的免疫排斥反映对移植的影响。结论：在探索应用何种材料能更有效地治疗关节软骨缺损的过程中，人们一直把希望寄托在比自体骨软骨更理想的替代材料上，在众多的替代材料中，同种异体骨软骨有其独特的优势和应用价值，尤其对大块及特定形态结构部位缺损的替代作用。随着同种异体骨软骨移植的免疫排斥、软骨保存、软骨退变等问题的进一步解决，必将使关节软骨缺损的治疗学产生革命性的发展。     

点种法移植软骨细胞修复关节软骨缺损

背景：生物性的重建虽能达到修复缺损,重建关节面的目的,但功能上难以与正常软骨一致。应用可降解的聚合物把移植的软骨细胞包埋起来进行移植,可能获得真正意义上的透明软骨。目的：观察以同种异体兔软骨细胞胶原包埋后,点种法移植软骨细胞修复关节软骨缺损的效果。方法：新西兰纯种兔制备膝关节全层软骨缺损后分为3组：分别进行胶原包埋软骨细胞点种法移植、单纯软骨细胞点种法移植和仅在大面积软骨缺损的软骨下钻孔。结果与结论：术后2,4,12,24周观察组织学动态变化,发现胶原包埋软骨细胞点种法移植组能获得透明软骨修复,而软骨细胞点种法组和单纯软骨下骨钻孔组缺损区仅为纤维组织填充,并且胶原包埋软骨细胞点种法移植组兔各期平均组织学和组织化学得分均高于其他两组（P〈0.01）。说明胶原包埋点种法软骨细胞移植能获得透明软骨修复,尤其适用于大面积软骨缺损。     

Characterization of costal cartilage and its suitability as a cell source for articular cartilage tissue engineering

Costal cartilage is a promising donor source of chondrocytes to alleviate cell scarcity in articular cartilage tissue engineering. Limited knowledge exists, however, on costal cartilage characteristics. This study describes the characterization of costal cartilage and articular cartilage properties and compares neocartilage engineered with costal chondrocytes to native articular cartilage, all within a sheep model. Specifically, we (a) quantitatively characterized the properties of costal cartilage in comparison to patellofemoral articular cartilage, and (b) evaluated the quality of neocartilage derived from costal chondrocytes for potential use in articular cartilage regeneration. Ovine costal and articular cartilages from various topographical locations were characterized mechanically, biochemically, and histologically. Costal cartilage was stiffer in compression but softer and weaker in tension than articular cartilage. These differences were attributed to high amounts of glycosaminoglycans and mineralization and a low amount of collagen in costal cartilage. Compared to articular cartilage, costal cartilage was more densely populated with chondrocytes, rendering it an excellent chondrocyte source. In terms of tissue engineering, using the self‐assembling process, costal chondrocytes formed articular cartilage‐like neocartilage. Quantitatively compared via a functionality index, neocartilage achieved 55% of the medial condyle cartilage mechanical and biochemical properties. This characterization study highlighted the differences between costal and articular cartilages in native forms and demonstrated that costal cartilage is a valuable source of chondrocytes suitable for articular cartilage regeneration strategies.     

同种异体组织工程预定形态软骨的研究

目的研究以聚羟基乙酸(Polyglycolicacid,PGA)为细胞支架同种异体预定形态组织工程化软骨在有免疫力的动物体内构建的可行性。方法取1周龄乳兔肋软骨和关节软骨,收集体外培养第3～4代的软骨细胞,接种于塑为管状和片状经多聚赖氨酸处理的PGA材料上。分别于6、12周取材,行大体和组织学观察评价。结果软骨细胞-PGA复合物体外培养1周有基质产生。种植6周后,管状和片状复合物生成软骨,结缔组织内可见炎细胞;12周时软骨细胞成熟。结论同种异体软骨细胞与PGA所形成的复合物在有免疫力的动物体内可构建出预定形态软骨。     

Recombinant adeno-associated virus vectors efficiently and persistently transduce chondrocytes in normal and osteoarthritic human articular cartilage

Successful gene transfer into articular cartilage is a prerequisite for gene therapy of articular joint disorders. In the present study we tested the hypothesis that recombinant adeno-associated virus (rAAV) vectors are capable of effecting gene transfer in isolated articular chondrocytes in vitro, articular cartilage tissue in vitro, and sites of articular damage in vivo. Using an rAAV vector carrying the Escherichia coli beta-galactosidase gene (lacZ) under the control of the cytomegalovirus (CMV) immediate-early promoter/enhancer (rAAV-lacZ), transduction efficiency exceeded 70% for isolated normal human adult articular chondrocytes, and osteoarthritic human articular chondrocytes. These were comparable to the transduction efficiency obtained with neonatal bovine articular chondrocytes. Transduction of explant cultures of articular cartilage resulted in reporter gene expression within the tissue of all three cartilage types to a depth exceeding 450 microm, which remained present until 150 days. When rAAV-lacZ vectors were applied to femoral chondral defects and osteochondral defects in vivo in a rat knee model, reporter gene expression was achieved for at least 10 days after transduction. These data suggest that AAV-based vectors can efficiently transduce and stably express foreign genes in articular chondrocytes, including chondrocytes of normal and osteoarthritic human articular cartilage. The data further suggest that the same rAAV vectors are capable of transducing chondrocytes in situ within their native matrix to a depth sufficient to be of potential clinical significance. Finally, the data demonstrate that these rAAV vectors are capable of effectively delivering recombinant genes to chondral and osteochondral defects in vivo.     

聚乙酸-聚乙醇酸共聚物复合同种异体细胞修复软骨缺损

背景:以自体骨髓间充质干细胞和软骨细胞作为种子细胞修复软骨缺损可达到理想效果,但存在细胞数量不足及二次创伤等问题。目的:观察同种异体骨髓间充质干细胞和软骨细胞与聚乙酸-聚乙醇酸共聚物复合修复关节软骨的可行性。方法:将15只新西兰大白兔随机分为实验组、对照组、空白组,制作关节软骨缺损模型,分别于骨缺损处植入同种异体骨髓间充质干细胞和同种异体软骨细胞与聚乙酸-聚乙醇酸共聚物复合体、自体骨髓间充质干细胞和自体软骨细胞与聚乙酸-聚乙醇酸共聚物复合体、聚乙酸-聚乙醇酸共聚物材料。结果与结论:术后12周苏木精-伊红及Masson三色染色显示,实验组软骨缺损处可见软骨细胞,呈圆形或多角形,柱状排列,软骨陷窝形成明显,可见大量细胞外基质沉积,修复组织显示出透明软骨样,与周围软骨结合好,与底层骨结合紧密;对照组与实验组无明显差别;空白组软骨缺损处可见纤维样细胞。说明同种异体骨髓间充质干细胞和软骨细胞与聚乙酸-聚乙醇酸共聚物复合可修复关节软骨缺损。     

Enhanced repair of articular cartilage defects in vivo by transplanted chondrocytes overexpressing insulin-like growth factor I (IGF-I)

Traumatic articular cartilage lesions have a limited capacity to heal. We tested the hypothesis that overexpression of a human insulin-like growth factor I (IGF-I) cDNA by transplanted articular chondrocytes enhances the repair of full-thickness (osteochondral) cartilage defects in vivo. Lapine articular chondrocytes were transfected with expression plasmid vectors containing the cDNA for the Escherichia coli lacZ gene or the human IGF-I gene and were encapsulated in alginate. The expression patterns of the transgenes in these implants were monitored in vitro for 36 days. Transfected allogeneic chondrocytes in alginate were transplanted into osteochondral defects in the trochlear groove of rabbits. At three and 14 weeks, the quality of articular cartilage repair was evaluated qualitatively and quantitatively. In vitro, IGF-I secretion by implants constructed from IGF-I-transfected chondrocytes and alginate was 123.2+/-22.3 ng/10(7) cells/24 h at day 4 post transfection and remained elevated at day 36, the longest time point evaluated. In vivo, transplantation of IGF-I implants improved articular cartilage repair and accelerated the formation of the subchondral bone at both time points compared to lacZ implants. The data indicate that allogeneic chondrocytes, transfected by a nonviral method and cultured in alginate, are able to secrete biologically relevant amounts of IGF-I over a prolonged period of time in vitro. The data further demonstrate that implantation of these composites into deep articular cartilage defects is sufficient to augment cartilage defect repair in vivo. These results suggest that therapeutic growth factor gene delivery using encapsulated and transplanted genetically modified chondrocytes may be applicable to sites of focal articular cartilage damage.     

Efficient lipid-mediated gene transfer to articular chondrocytes

We examined nonviral, lipid-mediated gene transfer methods as potential tools for efficient transfection of articular chondrocytes. Transfection conditions were determined for primary cultures of normal human articular, osteoarthritic human articular and normal bovine articular chondrocytes using a lacZ reporter gene construct with the commercially available cationic liposomes Cellfectin, DMRIE-C, LipofectAmine, Lipofectin, LipoTaxi, TransFast and the lipid-based reagent FuGENE 6. Optimized conditions were then evaluated in an ex vivo model of chondrocyte transplantation. FuGENE 6 transfection produced the maximum levels of transgene expression. Transfection efficiency was cell type specific and affected by DNA concentration, lipid/DNA ratio and the presence of hyaluronidase, a matrix-degrading enzyme. Analysis of X-gal staining demonstrated an efficiency of 41.0% in normal bovine articular chondrocytes, 20.7% in normal human articular chondrocytes and 7.8% in osteoarthritic human chondrocytes. Transfected chondrocytes were found to successfully populate the articular cartilage surface in explant cultures. Transplanted genetically modified chondrocytes adhered to the articular cartilage and continued to produce beta-galactosidase for 2 weeks. This evaluation and optimization of lipid-based gene transfer into articular chondrocytes may serve as a useful tool in studies of genes involved in articular cartilage damage and repair and as a potential delivery method for therapeutic genes. Gene Therapy (2000) 7, 286-291.     

关节软骨损伤后体外培养软骨细胞的功能变化

背景：关节软骨损伤可以影响软骨细胞功能,诱发创伤性骨关节炎。目的：观察关节软骨损伤后体外培养的软骨细胞功能的变化。方法：通过酶消化法分离培养高能量、低能量撞击后和正常兔膝关节透明软骨细胞,观察创伤能量对软骨细胞生存能力的影响;检测软骨细胞合成蛋白多糖和Ⅱ型胶原能力,检测细胞中白细胞介素1β和核转录因子κB mRNA表达水平,检测细胞合成白细胞介素1β和基质金属蛋白酶1的表达。结果与结论：高能量和低能量关节软骨损伤后,软骨细胞的存活率下降,原代细胞的贴壁细胞数量减少,贴壁时间延长,生长曲线下移,细胞甲苯胺蓝染色异染反应减弱,Ⅱ型胶原免疫组化染色强度减弱,软骨细胞中白细胞介素1β和核转录因子κB mRNA表达水平上升,细胞培养液中白细胞介素1β和基质金属蛋白酶1的质量浓度升高,其中高能量组效果更为显著（P〈0.05）。说明关节软骨损伤后软骨细胞的功能受到影响,受损程度与创伤强度及炎性细胞因子的表达相关。     

Reversibility of immobilization-induced articular cartilage degeneration after remobilization in rat knee joints

Joint immobilization is commonly used for the treatment of joint injuries, but it causes articular cartilage degeneration. The purpose of this study was to clarify the reversibility of immobilization-induced articular cartilage degeneration using rat knee joints. Immobilization of rat knee joints induces atrophic changes in the non-contact area, loss of chondrocytes in the contact area, and hypertrophy of chondrocytes in the transitional area of the articular cartilage. The unilateral knee joints of adult male rats were rigidly immobilized at 150° of flexion with a plate and screws for 1, 2, and 4 weeks. After the experimental periods, the fixation devices were removed and the rats moved freely for 16 weeks. Sham-operated rats were used as a control. Sagittal sections at medial midcondylar regions of the knee were assessed with histological and histomorphometric methods. Mechanical properties were assessed by measuring the sound speed with scanning acoustic microscope. Reduction of cartilage proteoglycan in the non-contact area was almost reversible, but hypertrophy of chondrocytes in the transitional area and loss of chondrocytes in the contact area were irreversible even at 1-week immobilization-remobilization group. Sound speed of the articular cartilage in the contact area was not restored. These results indicate that atrophic changes through decreased mechanical stress in the non-contact area were reversible, but loss of chondrocytes and hypertrophy of chondrocytes in the contact and transitional areas through increased mechanical stress by rigid immobilization were irreversible after remobilization. Clinicians should be aware that even a short-term rigid immobilization could cause irreversible articular cartilage damage.     

Overexpression of human insulin-like growth factor-I promotes new tissue formation in an ex vivo model of articular chondrocyte transplantation

Articular cartilage, the tissue that forms the gliding surface of joints, has a poor regenerative capacity. Insulin-like growth factor-I (IGF-I) is a polypeptide that is anabolic and mitogenic for cartilage. Transfection of articular chondrocytes with an expression plasmid vector containing the cDNA for human IGF-I under the control of the cytomegalovirus promoter/enhancer led to expression of the transgene and synthesis of biologically relevant amounts of IGF-I protein. Transplantation of transfected articular chondrocytes on to the surface of articular cartilage explants led to the formation of a new tissue layer on the cartilage explant surface. The new tissue was characterized by the presence of type II collagen and proteoglycan and by the absence of type I collagen, consistent with hyaline-like cartilage. The tissue formed by the chondrocytes expressing IGF-I was thicker and contained more cells than controls transfected with an expression plasmid vector containing the Escherichia coli (E. coli) beta-galactosidase (lacZ) gene. Transplantation of articular chondrocytes that overexpress human IGF-I also increased DNA synthesis and the synthesis of glycosaminoglycans by the underlying explant cartilage chondrocytes. These results identify a mechanism by which IGF-I may simultaneously promote chondrogenesis and shift cartilage homeostasis in an anabolic direction. The data further suggest that therapeutic growth factor gene transfer may be applicable to articular cartilage.