芍药舒筋片对大鼠膝骨关节炎软骨病理及COMP水平的影响

目的评价芍药舒筋片对膝骨关节炎大鼠关节软骨病理及COMP的影响。方法将50只大鼠随机分为假手术组,模型组,芍药舒筋片高、中、低剂量组。除假手术组外,其余组别大鼠采用经典前交叉韧带切断ACLT手术造模。造模成功后,各组采取相应的措施干预4周,检测COMP水平,并观察关节软骨病理变化情况。结果与假手术组比较,模型组Mankin病理评分及血清COMP含量差异均有统计学意义（P〈0．05）。与模型组比较,芍药舒筋片高、中、低剂量组Mankin病理评分差异有统计学意义（P〈0．05）,芍药舒筋片高剂量组血清COMP含量差异有统计学意义（P〈0．05）。结论芍药舒筋片对大鼠膝骨关节软骨有保护作用,可一定程度延缓手术形成的膝骨关节炎关节软骨退变。     

Endovascular treatment of Angio‐Seal™‐related limb ischemia—Primary results and long‐term follow‐up

Objectives : To investigate primary success rates and long term follow‐up of endovascular treatment of AngioSeal?‐related limb ischemia. Background : Current knowledge on optimal therapy of ischemic complications following application of AngioSeal? is limited. Methods : A single‐center prospectively maintained database was retrospectively interrogated and AngioSeal?—related complications requiring endovascular treatment over an 8‐year‐time period was identified. Results : Fifteen patients fulfilling the inclusion criteria were identified, resulting in an approximated incidence of 0.26% of all devices implanted at our institution. In all cases, the complication was managed successfully in the absence of complications. Eleven patients were treated with balloon angioplasty (PTA) and four with stent implantation because of suboptimal PTA results. Twelve patients were available for noninvasive vascular follow‐up examination for a median time of 40 months postinterventionally. Only two patients needed a second intervention consisting of balloon angioplasty due to symptomatic restenosis. At final follow‐up all patients were asymptomatic with no relevant restenosis. Conclusion : Endovascular treatment for AngioSeal?‐related limb ischemia with or without stent implantation results in an excellent immediate and long‐term clinical and hemodynamic outcome. © 2009 Wiley‐Liss, Inc.     

The influence of mechanical compression on the induction of osteoarthritis-related biomarkers in articular cartilage explants

OBJECTIVE: Macromolecules of the articular cartilage extracellular matrix released into synovial fluid, blood, or urine can serve as potentially useful biomarkers of the severity of osteoarthritis (OA). Biomechanical factors play an important role in OA pathogenesis, yet their influence on biomarker production is not well understood. The goal of this study was to examine the hypothesis that dynamic mechanical stress influences the release of these biomarkers from articular cartilage. METHODS: Explants of porcine cartilage were subjected to dynamic compression at 0.5 Hz for 24h at stresses ranging from 0.006 to 0.1 MPa. The concentrations of cartilage oligomeric matrix protein (COMP), keratan sulfate (KS measured as the 5 D 4 epitope), total sulfated glycosaminoglycan (S-GAG), and the KS (keratanase-digestible) and chondroitin sulfate (CS) (chondroitinase-digestible) fractions of S-GAG were measured. Radiolabel incorporation was used to determine the rates of proteoglycan and protein synthesis. RESULTS: The magnitudes of mechanical stress applied in this study induced nominal tissue strains of 4-23%, consistent with a range of physiological to hyperphysiologic strains measured in situ. COMP release increased in proportion to the magnitude of dynamic mechanical stress, while KS, CS and total S-GAG release increased in a bimodal pattern with increasing stress. Protein and proteoglycan synthesis were significantly decreased at the highest level of stress. CONCLUSION: Mechanical stress differentially regulates the turnover of distinct pools of cartilage macromolecules. These findings indicate that mechanical factors, independent of exogenous cytokines or other stimulatory factors, can influence the production and release of OA-related biomarkers from articular cartilage.     

补肾方、柔肝方与化痰方对膝骨关节炎滑膜细胞增殖及COMP表达的影响

目的：探讨补肾方、柔肝方和化痰方对膝骨关节炎滑膜细胞增殖及COMP表达的影响。方法：补肾方、柔肝方和化痰方含药血清培养早期和晚期滑膜细胞，MTS／PMS法测定OD值，hCOMP定量试剂盒测定COMP含量。结果：通过MTS／PMS法观察确定补肾方、柔肝方和化痰方含药血清培养滑膜细胞观察点在第5～7天；三方培养滑膜细胞OD值低于正常血清对照组（P≤0．05）。结论：补肾方、柔肝方与化痰方可以抑制体外培养早期和晚期膝骨关节炎患者滑膜细胞增殖，柔肝方可以降低体外培养滑膜细胞分泌液中COMP的浓度。     

Identification of sequence polymorphisms of the COMP (cartilage oligomeric matrix protein) gene and association study in osteoarthrosis of the knee and hip joints

Osteoarthrosis (OA) is a common cause of musculoskeletal disability characterized by late-onset degeneration of articular cartilage. Although several candidate genes have been reported, susceptibility genes for OA remain to be determined. Hereditary osteochondral dysplasias produce severe, early-onset OA and hence are models for common idiopathic OA. Among them are pseudoachondroplasia and multiple epiphyseal dysplasia, both of which are caused by mutations in the cartilage oligomeric matrix protein (COMP) gene. Therefore, COMP may be a susceptibility gene for OA. We screened for polymorphisms by direct sequencing of all exons of the COMP gene with their flanking intron sequences and the promoter region. We identified 16 polymorphisms, of which 12 were novel. Using six polymorphisms spanning the entire COMP gene, we examined the association of COMP in Japanese patients with OA of the knee and hip joints. Genotype and allele frequencies of the polymorphisms were not significantly different between OA and control groups, and there was no significant difference in haplotypes. These results do not support an association between COMP and OA in the Japanese population. Received: March 30, 2001 / Accepted: May 7, 2001     

Identification of nine novel mutations in cartilage oligomeric matrix protein in patients with pseudoachondroplasia and multiple epiphyseal dysplasia

Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (EDM1) are allelic disorders caused by mutations in the gene encoding cartilage oligomeric matrix protein (COMP). PSACH is a dominant condition characterized by disproportionate short stature, joint laxity, and early-onset osteoarthritis. EDM1 is a less severe skeletal dysplasia associated with average to mild short stature, joint pain, and early-onset osteoarthritis. COMP is an extracellular matrix protein present in cartilage, ligament, and tendon tissues. Here, we report on nine novel mutations in COMP causing PSACH and EDM1. Four of these mutations are in exons 13C and 14 where no previous mutations had been reported. One of those mutations was identified in two separate EDM1 families. In addition, we have identified the first case of PSACH resulting from an expansion of the five aspartates in exon 17B. We are also reporting a mutation in a third PSACH family with somatic/germline mosaicism. Therefore, this report increases the range of mutations that cause PSACH and EDM1 and provides additional regions to target for mutational analysis. Am. J. Med. Genet. 85:486–490, 1999. © 1999 Wiley-Liss, Inc.     

Effect of different running modes on the morphological,biochemical, and mechanical properties of articular cartilage

Mechanical loading plays an important role not solely in cartilage development, but also in cartilage degeneration. Its adaptation behavior to mechanical loading has not been clearly delineated. The aim of the study was to examine the effect of different running modes (with different muscle contraction types) on morphological, biochemical, and mechanical properties of articular cartilage in the knee of growing rats. Thirty‐six female Sprague–Dawley rats were randomly assigned into a nonactive age‐matched control (AMC), level (LEVEL), and 20° downhill (DOWN) running group (n = 12 each). Running groups were trained on a treadmill for 30 min/day, 5 days/week for 6 weeks. Immunohistochemical staining and analysis of expression for collagen II, collagen IX, cartilage oligomeric matrix protein (COMP), and matrilin‐3, histomorphometry of femoral cartilage height and femoral COMP staining height, and indentation testing of tibial articular cartilage were performed. Rats subjected to downhill running showed a significantly (P = 0.015) higher COMP staining height and a tendentially (P = 0.084) higher cartilage height in the high‐weight bearing area of femoral articular cartilage. Cartilage thickness, mechanical properties, and expression of cartilage network proteins in tibial cartilage remained unaffected by different running modes. Our data suggest that joint loading induced by eccentric muscle contractions during downhill running may lead to a site‐specific adaptation.     

Impact of knee joint loading on fragmentation of serum cartilage oligomeric matrix protein

The aim of the study was to examine the effect of mechanical knee joint loading on the fragmentation pattern of serum cartilage oligomeric matrix protein (COMP). Ten healthy men ran with knee orthoses that were passive or active (+30.9 N·m external flexion moments) on a treadmill (30 minute; v = 2.2 m/s). Lower-limb mechanics, serum COMP levels, and fragmentation patterns (baseline; 0, 0.5, 1, 2 hours postrunning) were analyzed. Running with active orthoses enhanced knee flexion moments, ankle dorsiflexion, and knee flexion angles (P < .05). There was an increase in serum COMP (+25%; pre: 8.9 ± 2.4 U/l; post: 10.7 ± 1.9 U/l, P = .001), COMP pentamer/tetramer (+88%; 1.88 ± 0.81, P = .007), trimer (+209%; 3.09 ± 2.65, P = .005), and monomer (+78%; 1.78 ± 0.85, P = .007) after running with passive orthoses and in serum COMP (+41%; pre: 8.5 ± 2.7 U/l; post: 11.3 ± 2.1 U/l, P < .001), COMP pentamer/tetramer (+57%; 1.57 ± 0.39, P = .007), trimer (+86%; 1.86 ± 0.47, P = .005), and monomer (+19%; 1.19 ± 0.34, P = .114) after running with active orthoses. Increased fragmentation might indicate COMP release from cartilage while running. Interestingly, 0.5 h up to 2 hours after running with passive orthoses, trimer (0.5 hour: 2.73 ± 3.40, P = .029; 2 hours: 2.33 ± 2.88, P = .037), and monomer (0.5 hour: 2.23 ± 2.33, P = .007; 1 hour: 2.55 ± 1.96, P = .012; 2 hours: 2.65 ± 2.50, P = .009) increased while after running with active orthoses, pentamer/tetramer (1 hour: 0.79 ± 0.28, P = .029), and trimer (1 hour: 0.63 ± 0.14, P = .005; 2 hours: 0.68 ± 0.34, P = .047) decreased. It seems that COMP degradation and clearance vary depending on joint loading characteristics.     

骨瓜提取物注射液联合双醋瑞因治疗骨关节炎的临床研究

目的探讨骨瓜提取物注射液联合双醋瑞因胶囊治疗骨关节炎的临床疗效。方法选取2017年2月—2018年2月在青海大学附属医院治疗的骨关节炎患者86例,依据用药的差别分为对照组(43例)和治疗组(43例)。对照组患者口服双醋瑞因胶囊,50 mg/次,2次/d;治疗组在对照组基础上静脉滴注骨瓜提取物注射液,100 mg加入250 mL生理盐水,1次/d。两组均治疗4周。观察两组患者临床疗效,同时比较治疗前后两组患者膝关节功能评分和血清学指标。结果治疗后,对照组临床有效率为79.07%,显著低于治疗组的95.35%,两组比较差异具有统计学意义(P0.05)。治疗后,两组骨关节指数评分(WOMAC)评分和VAS评分均显著降低(P0.05),膝关节评分量表(LKSS)评分显著升高(P0.05),且治疗组膝关节功能评分明显优于对照组(P0.05)。治疗后,两组血清白细胞介素-1β(IL-1β)、软骨寡聚基质蛋白(COMP)、环氧化酶-2(COX-2)和基质金属蛋白酶-3(MMP-3)水平均显著降低(P0.05),且治疗组上述血清学指标明显低于对照组,两组比较差异具有统计学意义(P0.05)。结论骨瓜提取物注射液联合双醋瑞因胶囊治疗骨关节炎可有效改善患者临床症状,降低机体炎症反应,具有一定的临床推广应用价值。