Differential responses to parathyroid hormone‐related protein (PTHrP) deficiency in the various craniofacial cartilages

PTHrP null mutant mice exhibit skeletal abnormalities both in the craniofacial region and limbs. In the growth plate cartilage of the null mutant, a diminished number of proliferating chondrocytes and accelerated chondrocytic differentiation are observed. In order to examine the effect of PTHrP deficiency on the craniofacial morphology and highlight the differential feature of the composing cartilages, we examined the various cartilages in the craniofacial region of neonatal PTHrP deficient mice. The major part of the cartilaginous anterior cranial base appeared to be normal in the homozygous PTHrP deficient mice. However, acceleration of chondrocytic differentiation and endochondral bone formation was observed in the posterior part of the anterior cranial base and in the cranial base synchondroses. Ectopic bone formation was observed in the soft tissue‐running mid‐portion of the Meckel's cartilage, where the cartilage degenerates and converts to ligament in the course of normal development. The zonal structure of the mandibular condylar cartilage was scarcely affected, but the whole condyle was reduced in size. These results suggest the effect of PTHrP deficiency varies widely between the craniofacial cartilages, according to the differential features of each cartilage. Anat Rec 255:452–457, 1999. © 1999 Wiley‐Liss, Inc.     

Nondestructive imaging of human cartilage glycosaminoglycan concentration by MRI.

Despite the compelling need mandated by the prevalence and morbidity of degenerative cartilage diseases, it is extremely difficult to study disease progression and therapeutic efficacy, either in vitro or in vivo (clinically). This is partly because no techniques have been available for nondestructively visualizing the distribution of functionally important macromolecules in living cartilage. Here we describe and validate a technique to image the glycosaminoglycan concentration ([GAG]) of human cartilage nondestructively by magnetic resonance imaging (MRI). The technique is based on the premise that the negatively charged contrast agent gadolinium diethylene triamine pentaacetic acid (Gd(DTPA)2-) will distribute in cartilage in inverse relation to the negatively charged GAG concentration. Nuclear magnetic resonance spectroscopy studies of cartilage explants demonstrated that there was an approximately linear relationship between T1 (in the presence of Gd(DTPA)2-) and [GAG] over a large range of [GAG]. Furthermore, there was a strong agreement between the [GAG] calculated from [Gd(DTPA)2-] and the actual [GAG] determined from the validated methods of calculations from [Na+] and the biochemical DMMB assay. Spatial distributions of GAG were easily observed in T1-weighted and T1-calculated MRI studies of intact human joints, with good histological correlation. Furthermore, in vivo clinical images of T1 in the presence of Gd(DTPA)2- (i.e., GAG distribution) correlated well with the validated ex vivo results after total knee replacement surgery, showing that it is feasible to monitor GAG distribution in vivo. This approach gives us the opportunity to image directly the concentration of GAG, a major and critically important macromolecule in human cartilage.     

A Pilot Study of Seamless Regeneration of Bone and Cartilage in Knee Joint Regeneration Using Honeycomb TCP

The knee joint is a continuous structure of bone and cartilage tissue, making it difficult to regenerate using artificial biomaterials. In a previous study, we succeeded in developing honeycomb tricalcium phosphate (TCP), which has through-and-through holes and is able to provide the optimum microenvironment for hard tissue regeneration. We demonstrated that TCP with 300 μm pore diameters (300TCP) induced vigorous bone formation, and that TCP with 75 μm pore diameters (75TCP) induced cartilage formation. In the present study, we regenerated a knee joint defect using honeycomb TCP. 75TCP and 300TCP were loaded with transforming growth factor (TGF)-β alone or bone morphogenic protein (BMP)-2+TGF-β with or without Matrigel and transplanted into knee joint defect model rabbits. 75TCP showed no bone or cartilage tissue formation in any of the groups with TGF-β alone and BMP-2+TGF-β with/without Matrigel. However, for 300TCP and BMP-2+TGF-β with or without Matrigel, vigorous bone tissue formation was observed in the TCP holes, and cartilage tissue formation in the TCP surface layer was continuous with the existing cartilage. The cartilage area in the TCP surface was larger in the group without Matrigel (with BMP-2+TGF-β) than in the group with Matrigel (with BMP-2+TGF-β). Therefore, honeycomb TCP can induce the seamless regeneration of bone and cartilage in a knee joint.     

膜联蛋白Ⅰ在关节软骨中的表达及意义

目的探讨膜联蛋白Ⅰ(ANNX-Ⅰ)在骨性关节炎患者关节软骨中的表达及意义。方法用蛋白免疫印迹法(western blotting)检测ANNX-Ⅰ在15例骨性关节炎患者和5例正常对照者关节软骨的表达,并进行比较。结果 ANNX-Ⅰ在骨性关节炎患者的表达(1.27±0.39)明显低于正常对照组(1.72±0.22),差异具有统计学意义(P<0.05)。结论 ANNX-Ⅰ可能在软骨细胞的凋亡和炎症过程中发挥重要作用。     

低温保护剂载入关节软骨过程的传质建模

掌握加载过程中软骨组织内部低温保护剂浓度的时空分布特性,这对合理设计加载程序进而成功保存关节软骨至关重要,为此构建描述低温保护剂载入关节软骨过程的扩散传质模型。根据二元扩散热力学模型,将有效扩散系数与无限稀释扩散系数进行关联,活度系数采用UNIFAC模型估算,扩散系数的浓度依赖性采用Vignes公式表示,无限稀释扩散系数采用Siddiqi-Lucas公式计算。对于二甲亚砜(Me₂SO)、甘油(GLY)、乙二醇(EG)和丙二醇(PG)这4种典型的低温保护剂(CPA),由模型计算得到的软骨组织内CPA的平均浓度与文献报道的实验值之间的平均相对偏差(MRE)和决定系数(R²)分别为1.90%～36.29%和0.959～0.998(Me₂SO),13.56%～19.19%和0.990～0.995(GLY),8.89%～22.09%和0.969～0.988(EG),5.35%～23.76%和0.971～0.992(PG)。结果表明,该模型能较好地适用于这4种CPA,可用于直接预测加载过程中软骨组织内部CPA浓度的时空分布,从而指导加载程序的设计与优化。     

耳廓软骨骨化一例

患者男,25岁,因双耳廓逐渐僵硬8个月于2017年2月9日来我科就诊。患者8个月前发现双耳廓触之僵硬,失去正常耳廓柔韧性,无明显自觉症状,否认外伤、昆虫叮咬及冻伤史。既往体健,否认糖尿病、肾脏病及甲状腺疾病,无家族性遗传病及相似疾病史……     

富血小板血浆修复生长期兔髁突软骨损伤后下颌骨生长发育的三维评估研究

目的　建立生长期髁突软骨及软骨下骨损伤动物模型,利用Materialise Proplan CMF 3.0软件对下颌骨进行三维测量,探讨富血小板血浆（PRP）对生长期髁突软骨损伤修复及维持下颌骨生长发育的作用。方法　生长期新西兰大白兔30只随机分为3组。PRP修复组（10只）建立髁突软骨及软骨下骨损伤动物模型后置入激活后的PRP;手术组（10只）建立髁突软骨及软骨下骨损伤动物模型;假手术组（10只）除不造成软骨及软骨下骨损伤外,其余与手术组相同。术后6周、12周对动物头颅进行螺旋CT扫描,采集SPCC格式数据。利用Materialise Proplan CMF 3.0软件对硬组织进行三维重建并分离上下颌骨,完整显露髁突的形态,确定标志点、参考平面及相应的测量指标,对测量结果进行统计学分析。结果　各个时间点手术组动物各项测量指标的测量值均小于假手术组与PRP修复组动物的（P < 0.05）;术后6周,PRP修复组动物的下颌升支高度、髁突长度、髁突宽度测量值均小于假手术组的（P < 0.05）;PRP修复组动物的下颌体长度、髁突高度测量值与假手术组动物的相比差异无统计学意义（P > 0.05）;术后12周PRP组动物的下颌升支高度、下颌体长度测量值均小于假手术组动物的（P < 0.05）,PRP修复组动物的髁突高度、髁突长度、髁突宽度测量值与假手术组动物的差异无统计学意义（P > 0.05）。结论　生长期髁突软骨损伤后,下颌骨生长发育相对停滞,髁突发生吸收。激活后的PRP可有效修复生长期髁突软骨损伤,维持下颌骨的正常形态,促进下颌骨及髁突的正常生长发育。