在体阻断软骨下营养对关节软骨影响的实验研究

背景：关节软骨无血管分布,其营养来自关节液和软骨下骨,哪条营养通路对关节软骨更为重要是学者们争论的焦点。目的：研究软骨下营养对关节软骨的影响,并探讨软骨下营养与骨关节炎的关系。方法：45只5个月龄雄性新西兰大白兔,建立股骨滑车骨软骨缺损的动物模型,并随机分为3组：自体骨软骨块移植组（Control组,n=15）;假手术组（Sham组,n=15）,用环钻在股骨滑车钻取骨软骨块,将其置入管状PVC内,原位回植;阻断软骨下营养组（DNBM组,n=15）,取出骨软骨后,将其置入帽状PVC内,原位回植。术后4周、8周、12周,每组5只（10膝）,取出膝关节进行大体评分、组织学评分、软骨厚度测量、凋亡染色（TUNEL染色）。结果：与Control组相比,大体评分结果提示,DNBM组软骨无明显退变;组织学评分结果提示,术后12周时DNBM组软骨明显退变（P〈0.005）;软骨厚度测量结果提示,术后8周、12周时DNBM组软骨厚度明显变小（P=0.00）;TUNEL染色结果提示,术后8周、12周时DNBM组关节软骨细胞凋亡明显增加（P〈0.01）。结论：软骨下营养是软骨的重要营养来源,失去软骨下营养,软骨会逐渐发生退变。     

Trimethylamine N‐oxide as a media supplement for cartilage tissue engineering

Supplements added to the culture media (e.g., growth factors and dexamethasone) have been successful in improving mechanical and biochemical properties of engineered cartilage towards native values. Trimethylamine N‐oxide (TMAO), a natural osmolyte found in shark cartilage, is thought to induce protein folding, and counteracts the destabilizing effect of the high concentrations of urea stored by sharks. The objective of this study was to investigate the use of TMAO as a media supplement for promoting growth of functional engineered cartilage in culture. In the first study, TMAO was added to the culture media for the first 14 days in culture and concentrations of 0–200 mM were evaluated. In the second study, TMAO was supplemented to the culture media following chondroitinase ABC digestion, which has been previously shown to mediate an increased collagen content in engineered cartilage. A dose‐dependent response was observed with improved mechanical and biochemical properties for engineered constructs cultured with TMAO at concentrations of 5–100 mM. The Young's modulus of digested constructs cultured in TMAO was 2× greater than digested constructs cultured in the control medium and recovered to undigested control levels by day 42. In conclusion, these initial studies with TMAO as a media supplement show promise for improving the compressive mechanical properties, increasing extracellular matrix production, and increasing the recovery time following chABC digestion. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1898–1905, 2012     

Critical‐size defect induces unicompartmental osteoarthritis in a stable ovine knee

Animal models simulating osteoarthritis are frequently associated with irreversible changes in biomechanics. Although these models successfully induce osteoarthritis, results of experimental repair procedures are impaired by biomechanical problems. The aim of this study was to define the critical size of a chondral lesion to induce unicompartmental osteoarthritis in a stable joint. Sixteen sheep were randomly divided into four treatment groups. A cartilage defect (7‐ or 14‐mm diameter) was created in the weight‐bearing zone of the medial femoral condyle. The sheep were mobilized for 6 or 12 weeks. Osteoarthritis was determined by gross assessment, India ink staining, histology (Mankin score), and analysis of COMP in the serum. In the 6‐week group, only minor osteoarthritis was registered for either defect size. After 12 weeks, the 14‐mm defect induced minor osteoarthritis at the femoral condyle and caused significant degenerative changes at the tibial articular cartilage and the meniscus. The 7‐mm defect created focal unicompartmental osteoarthritis at the medial femoral condyle and minor degenerative changes at the corresponding tibia. A 7‐mm full‐thickness chondral defect with a weight‐bearing regimen of 12 weeks induced local osteoarthritis at the medial compartment in an otherwise stable joint as aimed. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:214–220, 2012     

自体鼻中隔软骨游离移植亚洲人鼻延长术

目的 探讨自体中隔软骨移植,改变鼻短小鼻尖圆钝的外形、延长鼻长度、改善鼻尖外形及鼻唇角.方法 松解与塑造鼻翼软骨形后,切取自体鼻中隔软骨行L状移植及帽状移植,并辅以埋线塑形等手段.结果 共完成此类手术345例,经6个月至4年术后随访,均获得满意效果.结论 采用在鼻中隔下端与鼻翼软骨穹窿部行鼻中隔软骨移植的方法加长鼻长度,疗效可靠,且自体鼻中隔软骨取材方便、损伤小、不易发生感染及排异等并发症,值得推广.     

经肘前入路软骨钉治疗肱骨小头骨折

目的探讨经肘前人路软骨钉治疗肱骨小头骨折内固定手术的方法和疗效。方法 2008年6月至2011年8月,采用经肘关节前侧＂S＂形入路可吸收软骨钉内固定治疗肱骨小头骨折12例,男8例,女4例,年龄12～52岁,平均28.5岁,Ⅰ型骨折5例,Ⅱ型骨折3例,Ⅲ型2例,Ⅳ型2例;其中有3例合并有桡骨小头骨折,1例合并有尺骨冠状突骨折。结果随访6～36个月,平均25个月。骨折临床愈合时间4～10周,平均6周。根据Morrey肘关节功能评分标准,良好（满意）9例,一般3例,无骨不连及肱骨小头缺血性坏死发生。结论肘前人路损伤小,暴露清楚,可直视下对肱骨小头的骨折块进行解剖复位;可吸收软骨钉对关节软骨面的损伤小,固定牢靠,可早期进行功能锻炼,无需二次取出,有利于肘关节功能的良好恢复。     

MR pharmacokinetic modeling of the patellar cartilage differentiates normal from pathological conditions

PURPOSE: To study the pharmacokinetic parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the patellar cartilage under normal and pathological conditions. MATERIALS AND METHODS: DCE-MRI was obtained in 22 cases. There were 17 patients with degenerative patellar conditions (eight with chondromalacia and nine with osteoarthritis) and five normal subjects. The cartilage pharmacokinetic parameters of K(trans) (vascular permeability), k(ep) (extraction ratio), upsilon(e) (extravascular extracellular space [EES] volume fraction), and upsilon(p) (intravascular space volume fraction) were extracted. RESULTS: Statistically significant differences were observed between the different groups (normal cartilage, chondromalacia and osteoarthritis) for K(trans) and upsilon(e). K(trans) values were (mean +/- SD) 1.06 +/- 0.62, 11.97 +/- 8.91, and 21.21 +/- 16.03 mL x minute(-1) x 100 mL(-1) (P < 0.02), respectively; and upsilon(e) values were 0.71 +/- 0.69, 3.59 +/- 2.21, and 10.51 +/- 8.20% (P < 0.002). Reproducibility of the pharmacokinetic calculations was assessed with a second set of analyses of 10 random cases one week after the first analysis, showing a test-retest root mean square (RMS) coefficient of variation of 9.78% for K(trans) and 14.72% for upsilon(e). CONCLUSION: The vascular permeability and EES fraction of cartilage increases with the severity of the degeneration. Pharmacokinetic models allow to study the vascular properties of the cartilage and may have applications as a surrogate index in longitudinal studies to quantify the evolution of drug trials.     

Rapid 3D-T(1) mapping of cartilage with variable flip angle and parallel imaging at 3.0T

PURPOSE: To rapidly acquire T(1)-weighted images using a three-dimensional fast low angle shot (3D FLASH) sequence in combination with generalized autocalibrating partially parallel acquisitions (GRAPPA) and variable flip angle (VFA) method at 3.0T. MATERIALS AND METHODS: 3D T(1) maps of model systems (gadolinium [Gd] and agarose phantoms), bovine cartilage, and human subjects were constructed on a 3.0T clinical whole-body MR scanner. The T(1) values of model systems measured using the 2D inversion-recovery fast-spin-echo (IR-FSE) sequence were considered as a reference method to validate the rapid 3D method for comparison. RESULTS: The root mean square coefficient of variation percentage (RMS-CV%) of the median T(1) of agarose phantom across different acquisition methods was approximately 6.2%. The RMS-CV% of the median T(1) of bovine cartilage across different acquisition methods was approximately 4.1%. The RMS-CV% of median T(1) of the cartilages among the subjects was between approximately 7.3% to 11.1%. In our study, rapid 3D-T(1) mapping with VFA and parallel imaging with different acceleration factors (AFs) (AF = 1, 2, 3, and 4) seems to have no obvious influence on the T(1) mapping (before and after contrast agent administration). CONCLUSION: The preliminary results demonstrate that it is possible to quantify 3D-T(1) mapping of the whole knee joint (with 0.7 mm(3) isotropic resolution) under approximately five minutes with excellent in vivo reproducibility at 3.0T.     

应用磁共振软骨T2图成像定量测定退变兔膝关节软骨

目的:探讨T_2图成像技术在检测关节软骨退变早期的应用价值。材料和方法:选用20只新西兰大白兔,随机分为甲、乙、丙、丁四组。甲组左膝关节行常规磁共振成像,扫描结束后即刻处死,取股骨髁软骨行苏木素和伊红染色(HE)、阿利辛兰染色(AB)及蛋白多糖含量测定。乙、丙、丁各组每只兔左膝关节内注射0.2ml(10U)木瓜蛋白酶。乙、丙、丁各组于注射木瓜蛋白酶前及注射后分别于24h、48h、72h先行相同常规磁共振成像及T_2图成像,取感兴趣点,测定关节软骨T_2弛豫时间值并取平均值,对每组数据进行t检验。扫描结束后处死动物,取左膝股骨髁部软骨行大体观察、HE、AB染色及蛋白多糖含量测定。结果:注射木瓜蛋白酶后24h、48h,蛋白多糖含量与甲组比较,统计学均有差异(P=0.048和0.045,P<0.05),注射后72h,统计学没有差异(P=0.455,P>0.05)。T_2图像软骨色阶由注射前的黄红色转为注射后的红色,注射木瓜蛋白酶后24h、48h、72h的T_2弛豫率分别升高了30.14ms,20.92ms和16.17ms。经t检验后,注射后24h与注射前差异具有统计学意义(P= 0.04,P<0.05)。结论:本研究采用的T_2图成像技术能够通过定量检测T_2弛豫时间值反映软骨退变早期软骨内的生化改变。     

Induction of apoptosis of articular chondrocytes and suppression of articular cartilage proteoglycan synthesis by heat shock

We investigated cellular and matrix responses of articular cartilage to heat shock. Rat articular cartilage was pretreated at 37 degrees C for 24 h before being exposed to 48 degrees C for 10 min and subsequently incubated at 37 degrees C for 1, 2, 4, 7, 10, and 14 days. Following heat shock, a terminal deoxynucleotidyl transferase nick end labeling assay showed that articular chondrocyte apoptosis appeared at day 1, peaked at day 7, and declined by day 14. Analysis by transmission electron microscopy confirmed that the chondrocytes had characteristic morphological features of apoptosis; immunohistochemical staining revealed that caspase-3 activity in chondrocytes increased, 3-B-3-positive articular chondrocytes decreased in number, and the expression of 3-B-3 native epitope in articular chondrocytes was reduced. Safranin-O staining revealed that depletion of proteoglycans in the matrix was not found in any group. Morphological and biochemical evidence from this study suggested that heat shock at 48 degrees C induced articular chondrocyte apoptosis and suppressed proteoglycan synthesis of articular cartilage in vitro. This study thus provides evidence of the onset of osteoarthritis induced by heat shock and a basis for choosing a temperature at which malignant bone tumor cells can be killed with minimal damage to articular cartilage.