Evaluation of complete and incomplete subscapularis tendon tear on preoperative magnetic resonance imaging.

BACKGROUND: This study aims to evaluate the significance of preoperative magnetic resonance imaging findings to predict subscapularis tear confirmed at arthroscopic surgery. METHODS: Sixty-four consecutive shoulders that underwent preoperative magnetic resonance imaging examination and arthroscopic shoulder operations were retrospectively reviewed. Under arthroscopic examination, complete subscapularis tear was defined as a full-thickness tear and incomplete subscapularis tear as tendon detachment larger than 5 mm from the insertion on the joint side. RESULTS: In arthroscopic findings, they were included 11 shoulders with complete subscapularis tear, 13 with incomplete subscapularis tear, and the remaining 28 shoulders without subscapularis tear. Subscapularis discontinuity by axial magnetic resonance imaging had the highest sensitivity and specificity in detecting complete subscapularis tear compared with other magnetic resonance imaging findings. Long head biceps subluxation or dislocation showed significantly higher prevalence in the complete and incomplete subscapularis tear groups than in the group with no tear. Incomplete subscapularis tear groups had a higher incidence of superior subscapularis recess fluid, and this fluid was present in all the shoulders with incomplete subscapularis tear. CONCLUSIONS: The presence of subscapularis discontinuity is useful for diagnosis of complete subscapularis tear. In addition, in cases of incomplete subscapularis tear, the presence of superior subscapularis recess fluid had 100% sensitivity. Thus, this finding may be a characteristic diagnosis of subscapularis tear including incomplete tear.

Evaluating various radiographic methods of shoulder joint damage in patients with rheumatoid arthritis receiving biological disease-modifying antirheumatic drugs.

OBJECTIVES: This study aims to clarify shoulder joint damage in rheumatoid arthritis patients receiving biological disease-modifying antirheumatic drugs (bDMARDs) and the relationship between joint damage and clinical factors. PATIENTS AND METHODS: In this retrospective study conducted between April 2005 and December 2008, 36 shoulders in 19 patients (2 males, 17 females; mean age: 58.9 years; range 42 to 75 years) were evaluated at baseline and two years after the initiation of bDMARD therapy with infliximab (n=14) or etanercept (n=5). Standard anteroposterior radiographs of the shoulder joints were taken at baseline and two years after institution of biological therapy. Structural damage in the shoulder joints was assessed using the Larsen scoring method, the medial displacement index (MDI), and the upward migration index (UMI). RESULTS: There was a significant correlation between MDI, UMI, and Larsen grade before biological therapy. Univariate analysis revealed that the disease activity score 28-count erythrocyte sedimentation rate (ESR) at baseline (odds ratio [OR]: 4.298) was associated with progression of MDI. But multivariate logistic regression revealed that there was no association with the progression of MDI. Univariate analysis revealed that ESR at baseline (OR: 0.967) and matrix metalloproteinase-3 (MMP-3) at baseline (OR: 0.996) were associated with the progression of UMI. Multivariate logistic regression revealed that MMP-3 at baseline (OR: 0.994) was independently associated with the progression of UMI. CONCLUSION: Medial displacement index and UMI correlated with the Larsen grade of the shoulder joint strongly and moderately, respectively. This study suggests that MDI and UMI may help to evaluate radiographic progression of damage in shoulder joints in patients on bDMARDs, which is difficult to detect using the Larsen grade.

Intraoperative patellar tendon strain: predicting the range of knee flexion after total knee arthroplasty.

BACKGROUND: The preoperative range of motion is an important factor that influences the range of motion after total knee arthroplasty. Because the length and tightness of the extensor mechanism are extracapsular elements with an influence on knee flexion, it is reasonable to assume that the tension of the knee extensor mechanism during surgery has a considerable impact on the postoperative range of motion. The purpose of this study was to determine the influence of the tightness of knee extensor mechanism on postoperative knee flexion. METHODS: In 18 knees undergoing posterior-stabilized type total knee arthroplasty, we measured the longitudinal strain on the patellar tendon with all the components in position during passive knee flexion up to 135 degrees . The patellar tendon strains measured during surgery were compared with the preoperative maximum knee flexion angle and postoperative maximum knee flexion angle at 1 year. RESULTS: There was a significant inverse correlation between the patellar tendon strain during surgery at 60 degrees (r = -0.54, P < 0.05), 90 degrees (r = -0.55, P < 0.05), or 135 degrees of flexion (r = -0.65, P < 0.05) and postoperative knee flexion. CONCLUSIONS: The results indicated that subjects with high intraoperative patellar tendon strain during passive flexion of the knee had more restricted postoperative knee flexion. Therefore, the tightness of the knee extensor mechanism measured at total knee arthroplasty is a good predictor of maximum postoperative range of flexion.

Joint gap changes with patellar tendon strain and patellar position during TKA.

UNLABELLED: Balancing of the joint gap in extension and flexion is a prerequisite for success of a total knee arthroplasty. The joint gap is influenced by patellar position. We therefore hypothesized the state of the knee extensor mechanism (including the patellar tendon) would influence the joint gap. In 20 knees undergoing posterior-stabilized type total knee arthroplasties, we measured the joint gap and the patellar tendon strain from 0 degrees to 135 degrees flexion with the femoral component in position. When the patella was reduced, the joint gap was decreased at 90 degrees and 135 degrees (by 1.9 mm and 5.5 mm, respectively) compared with the gap with the patella everted. The patellar tendon strain increased with knee flexion. Patellar tendon strain at 90 degrees flexion correlated with the joint gap difference with the patella in everted and reduced positions. This suggests that in addition to the collateral ligaments, the knee extensor mechanism may have an influence on the joint gap. Therefore, accounting for extensor mechanism tightness may be important in achieving the optimal joint gap balance during total knee arthroplasty. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Gas6, a new regulator of chondrogenic differentiation from mesenchymal cells.

The mesenchymal cell line C3H10T1/2 can be preferentially induced toward chondrogenesis by culturing as a micromass in the presence of bone morphogenetic protein 2. To screen new regulator genes for chondrogenic differentiation, we performed differential display polymerase chain reaction and identified growth arrest-specific 6 (Gas6) as a gene that was clearly downregulated by this induction of chondrogenic differentiation. Blockage of Gas6 mRNA expression by siRNA remarkably enhanced the chondrogenic differentiation, while stimulation with recombinant Gas6 inhibited the mRNA expressions of type II collagen (Col2a1) and aggrecan. Gas6 signaling activated the phosphorylation of ERK1/2, SAPK/JNK, and Akt, but not p38 MAPK. These results suggest that Gas6 negatively regulates chondrogenic differentiation, at least through the MAPK pathway.

PEA3 cooperates with c-Jun in regulation of HER2/neu transcription.

HER2/neu overexpressing breast tumors exhibit an increase in polyomavirus enhancer activator 3 (PEA3) expression. We examined the relationship between HER2/neu transcriptional activation and PEA3 in cooperation with c-Jun. HER2/neu promoter activity was decreased by deleting PEA3 binding site, and was downregulated when the PEA3 binding site was mutated. PEA3 and c-Jun each weakly enhanced luciferase expression of the HER2/neu promoter. However, the HER2/neu promoter response to PEA3 was considerably enhanced by c-Jun. Thus, we examined the interaction of PEA3 with c-Jun by the two-hybrid system, the transcriptional activity of PEA3 was specifically enhanced by c-Jun. When PEA3, c-Jun and coactivator p300 were cotransfected in MCF7 cells, the transcriptional activity of HER2/neu was increased by up to 20-fold. PEA3 and c-Jun-induced transcription of HER2/neu promoter was repressed by cotransfection of the dominant negative of p300. These results suggest that PEA3 and c-Jun stimulated synergistically the HER2/neu gene transcription with p300.

A large-scale genetic association study of ossification of the posterior longitudinal ligament of the spine.

Research to date has identified several genes that are implicated in the etiology of ossification of the posterior longitudinal ligament of the spine (OPLL); however, their pathogenetic relevance remains obscure. The aim of this study is to identify susceptibility genes for OPLL through a large-scale case-control association study and to re-examine previously reported associations. A total of 109 single nucleotide polymorphisms (SNPs) in 35 candidate genes were genotyped for 711 sporadic OPLL patients and 896 controls. The differences in allelic and genotypic distribution between patients and controls were assessed using the chi (2) test with Bonferroni's correction. We also analyzed the association by separating patients into subgroups according to sex, age and the number of ossified vertebrae. The nominal P values fell below 0.05 for five SNPs in three genes. An intronic SNP in the TGF3 gene (P=0.00040) showed the most significant association. Previously reported associations of COL11A2, NPPS and TGFB1 with OPLL could not be reproduced. Further, no significant associations were detected in stratified analyses based on sex, age or the number of ossified vertebrae. TGFB3 warrants further investigation because it is located within a genomic region that has been positively linked with OPLL.

BMP-2 prevents apoptosis of the N1511 chondrocytic cell line through PI3K/Akt-mediated NF-kappaB activation.

The signal transduction pathway by which bone morphogenetic protein-2 (BMP-2) regulates apoptosis in chondrocytes remains largely unknown. We investigated the involvement of phosphatidylinositol 3-kinase (PI3K)/Akt-mediated NF-kappaB activation by BMP-2 stimulation in the modulation of this antiapoptotic process in a chondrocytic cell line, N1511. BMP-2 prevented apoptosis through the inhibition of caspase-3 and -9 and an increase in Bcl-xL expression, and this antiapoptotic effect was inhibited by Noggin. Not only was NF-kappaB p65 activated transiently in the early phase (5-15 min) after treatment with BMP-2 but p65 at serine 536 was phosphorylated from 5 min as well. Akt was rapidly phosphorylated in response to BMP-2 treatment; however, the inhibition of PI3K by Wortmannin markedly reduced the phosphorylation of Akt by BMP-2. Wortmannin also decreased the NF-kappaB transcriptional activity that was up-regulated by BMP-2. Thus, BMP-2-induced NF-kappaB activation is mediated by PI3K/Akt signaling. Wortmannin treatment inhibited the antiapoptotic effect of BMP-2. These data indicate that BMP-2 can utilize a new signal transduction pathway in the NF-kappaB activation system, which plays a crucial role in the survival of the N1511 chondrocytic cell line.

Association between polymorphism of the transforming growth factor-beta1 gene with the radiologic characteristic and ossification of the posterior longitudinal ligament.

STUDY DESIGN: A study was conducted to examine the relation between the transforming growth factor-beta1 (TGF-beta1) polymorphism (T-->C transition in the signal sequence) and ossification of the posterior longitudinal ligament (OPLL). OBJECTIVE: To investigate the association between the polymorphism of TGF-beta1 and the radiologic characteristics of OPLL. SUMMARY OF BACKGROUND DATA: Ossification of the posterior longitudinal ligament has a strong genetic background. Several genes contribute to the expression of OPLL. Transforming growth factor-beta1 is present in the ossified matrix and chondrocytes of cartilage adjacent to areas of OPLL. METHODS: The difference in the TGF-Tbeta1 allele distribution ("TT," "TC," and "CC") between 369 patients with OPLL and 258 control subjects was assessed. The relations between the allele frequency and radiologic features of OPLL involving the cervical, thoracic, and lumbar spine and the width of the ossification area were evaluated. RESULTS: There was no statistical difference with respect to the type of OPLL and the width of the ossification area for the TGF-Tbeta1 allele between the OPLL and the control groups. However, in the patients with "TC" or "CC" alleles, OPLL frequently was found in the cervical, thoracic, and/or lumbar spine. CONCLUSIONS: Transforming growth factor-beta1 polymorphism is not a factor associated with the occurrence of OPLL, but rather a factor related to the area of the ossified lesion. The "C" allele might be a risk factor for patients with OPLL in other areas in addition to the cervical lesion.

Significance of bone formation markers in patients with ossification of the posterior longitudinal ligament of the spine.

STUDY DESIGN: Serum concentrations of bone formation markers were correlated with the type, location, and progression of ossification of the posterior longitudinal ligament. OBJECTIVE: To determine the relation between bone formation markers and ossification of the posterior longitudinal ligament. SUMMARY OF BACKGROUND DATA: Few reports have correlated bone formation markers with ossification of the posterior longitudinal ligament. METHODS: In this study, 43 patients with cervical ossification of the posterior longitudinal ligament and myelopathy underwent laminoplasty. The patients were observed for more than 10 years, after which plain radiographs and tomograms of the cervical region were taken. The radiographs were selectively performed to address thoracic and lumbar ossification of the posterior longitudinal ligament. Serum concentrations of bone formation markers (intact osteocalcin, osteocalcin, carboxyterminal propeptide of human type 1 procollagen, and bone-specific alkaline phosphatase) were measured and correlated with these radiographic studies. RESULTS: A positive correlation was observed between intact osteocalcin, osteocalcin, and carboxyterminal propeptide of human type 1 procollagen in patients with combinations of cervical, thoracic, or lumbar ossification of the posterior longitudinal ligament. CONCLUSIONS: Serum concentrations of intact osteocalcin, osteocalcin, and carboxyterminal propeptide of human type 1 procollagen may reflect the activity of general ectopic bone formation in patients with ossification of the posterior longitudinal ligament.