Comparison of joint awareness after medial unicompartmental knee arthroplasty and high tibial osteotomy: a retrospective multicenter study.

INTRODUCTION: Unicompartmental knee arthroplasty (UKA) and high tibial osteotomy (HTO) are established treatments for medial compartment osteoarthritis (OA) or osteonecrosis (ON) of the knee joint, and the predominance of either procedure is inconclusive. We compared the awareness of the knee after UKA and HTO using the Forgotten joint score-12 (FJS). MATERIALS AND METHODS: This was a retrospective, multicenter study. Ninety-six knees of 90 patients who received UKA or HTO and were followed-up for at least 1 year were analyzed. Postoperative FJS was compared between the two groups and evaluated for the effect of patient-related factors and clinical outcomes. Multiple linear regression analysis was performed to predict FJS. RESULTS: There was no significant difference in the FJS between the UKA and HTO groups (p = 0.24). FJS did not correlate with any of the patient-related factors. There was a correlation between the FJS and each item of the Knee Injury and Osteoarthritis Outcome Scores (KOOS) and Lysholm Knee Scoring Scale (LKS). In multiple linear regression analysis, lower BMI, the diagnosis of OA Kellgren-Lawrence (KL) grade ≥ 3, and ON were significant predictors of better FJS. In both groups, FJS was correlated with each item of the KOOS and LKS. Internal consistency in terms of Cronbach's alpha was excellent. CONCLUSIONS: There was no significant difference in FJS between patients who underwent UKA and HTO. Lower BMI, the diagnosis of OA KL grade ≥ 3, and ON were significant predictors of better FJS.

Age-dependent differences in response to partial-thickness cartilage defects in a rat model as a measure to evaluate the efficacy of interventions for cartilage repair.

The objectives of this study are (1) to examine age-dependent longitudinal differences in histological responses after creation of partial-thickness articular cartilage defects (PTCDs) in rats and to use this model (2) to objectively evaluate the effectiveness of interventions for cartilage repair. Linear PTCDs were created at a depth of 100 µm in the weight-bearing region of the medial femoral condyle in rats of different ages (3 weeks, 6 weeks, 10 weeks and 14 weeks). One day, one week, two weeks, four weeks and twelve weeks after PTCD generation, spontaneous healing was evaluated histologically and immunohistochemically. Effects of interventions comprising mesenchymal stem cells (MSCs) or platelet-rich plasma (PRP) or both on 14-week-old PTCD rats were evaluated and compared with natural courses in rats of other ages. Younger rats exhibited better cartilage repair. Cartilage in 3-week-old and 6-week-old rats exhibited nearly normal restoration after 4-12 weeks. Cartilage in 14-week-old rats deteriorated over time and early signs of cartilage degeneration were observed. With injection of MCSs alone or MSCs + PRP, 14-week-old PTCD rats showed almost the same reparative cartilage as 6-week-old rats. With injection of PRP, 14-week-old PTCD rats showed almost the same reparative cartilage as 10-week-old rats. This model will be of great use to objectively compare the effects of interventions for small cartilage lesions and may help to advance the development of disease-modifying osteoarthritis drugs.

Comparison of meniscal extrusion and osteophyte formation at the intercondylar notch as a predictive biomarker for incidence of knee osteoarthritis-Data from the Osteoarthritis Initiative.

BACKGROUND: Medial meniscal extrusion (ME) is a biomarker to predict later development of knee osteoarthritis (KOA). On the other hand, we have reported osteophyte formation at the posterior condylar notch of the femur served as a biomarker for the same purpose. The purpose of this study is to compare capacity of the two biomarkers in predicting KOA development. METHODS: Two cohort of knees were established utilizing publicly available data from the Osteoarthritis Initiative (OAI). No OA group (NOA) consisted of knees that were grade 0 or 1 on Kellgren and Lawrence grade (K/L) both at baseline and 48 months later, and pre-radiographic-OA group (PROA) consisted of knees that were grade 0 or 1 at baseline but grade ≥2 48 months later. Baseline MR images were evaluated in terms of ME and osteophyte formation at the posterior condylar notch. ME was evaluated both by meniscus subluxation index (MSI) indicating the ratio of the extruded width of the medial meniscus to the width of medial meniscal body and by the medial radial displacement (MRD) indicating actual extruded width. The size of the osteophyte was assessed using a semi-quantitative whole-organ magnetic resonance imaging score (WORMS). The predictive accuracy of KOA was assessed by the area under the receiver operating characteristic curve (AUC) and optimal cutoff was determined for each parameter. RESULTS: The AUC for MSI was 0.654 (0.561-0.748: 95% CI) and the cutoff value was determined as 17%. That for MRD was 0.677 (0.584-0.770) and the cutoff value was 2.2 mm. The AUC for the WORMS score at the posterior condylar notch was 0.667 (0.579-0.756) and the cutoff value was 2. CONCLUSIONS: Similar predicting capacity of KOA development was found both in ME and osteophyte formation at the posterior condylar notch. Using these simple parameter, mas-screening for KOA development would be possible.

Evaluating different closed loop graft preparation technique for tibial suspensory fixation in ACL reconstruction using TightRope™.

In most anterior cruciate ligament (ACL) reconstructions, grafts are fixed to the femoral side first followed by the tibial side. Various techniques have been reported to achieve optimal tension on the grafts, but once the grafts are fixed it is difficult to adjust graft tension further. To enable post fixation tension control we have invented a new graft configuration using an adjustable loop-device (TightRopeTM, Arthrex, FL, USA) on the tibial side. In this paper, biomechanical properties of this configuration using soft tissue were examined in terms of graft diameter and various suture techniques (referred to as base suture) to make a closed circle to support TightRopeTM. Two experiments were conducted under different conditions. In each experiment, cyclic load, followed by a pull-to-failure load, was applied to the grafts and elongation and failure mode were recorded. (1) To evaluate the effects of diameter, 5.0 or 6.0 mm grafts were prepared by a single locking loop stitch as the base suture (SLL5, SLL6). (2) To evaluate different base sutures, 5.0 mm tendons were used, and grafts were prepared using five kinds of base sutures (SLL, ZLL: zigzag locking loop, DZLL: double zigzag locking loop, DK: double Krackow, DK w/o TR: double Krackow without TightRopeTM). In the first experiment, tearing was observed in 2 of 6 cases in the SLL5 test group, whereas no tearing was observed with SLL6. In the second experiment, no tearing was observed with DZLL or DK. Elongation was smaller in these two groups compared to the other groups. Mechanical strength decreases with a smaller graft diameter. Biomechanical properties differed with different base sutures and, among them, the double-zigzag-suture stitch and double Krackow provided less elongation and higher ultimate load in this graft configuration.

Comparative Analysis of Gene Expression between Cartilage and Menisci in Early-Phase Osteoarthritis of the Knee-An Animal Model Study.

Cartilage degeneration is believed to be the primary event in the development of osteoarthritis (OA). On the other hand, meniscal degeneration is observed with high prevalence, and some researchers have pointed out that pathological changes in menisci precede that of cartilage. The purpose of the present study is to investigate comprehensive gene expression pattern of cartilage and menisci in the initial phase of surgically induced OA and to compare them. Secondary OA was surgically induced in 10-week-old male Wistar rats by anterior cruciate ligament transection (ACLT). Articular cartilage and menisci were separately dissected from six ACLT- and six sham-operated rats. Each specimen was analyzed by microarray, histological, and immunohistochemical analysis 3 weeks after surgery. Of the 36,685 transcripts detectable by microarray, the number of upregulated transcripts in ACLT menisci was >2.5-fold compared with that in ACLT menisci in any given threshold. Cluster analysis using the Database for Annotation Visualization and Integrated Discovery (DAVID) showed genes related to OA, such as response to stimulus, angiogenesis, and apoptosis, which were predominantly found in menisci in ACLT rats. Representative proteases including Adamts2, 4, Mmp2, 12, 13, 14, 16, extracellular matrix genes including versican (Vcan), lumican (Lum), syndecan1 (Sdc1), and Prostaglandin endoperoxide synthase2 (Ptgs2) were up-regulated in menisci, but were not up-regulated in cartilage. Our results indicated that the molecular changes that occurred in menisci preceded those occurred in cartilage in the very early phase of surgically induced OA models.

Post-traumatic chylous knee effusion.

Chylous joint effusion is a rare condition in which synovial fluids containing large amounts of lipids take on a milky appearance as a result. We report on a 19-year-old male patient with posttraumatic chylous knee effusion. Several days after striking his knee against the ground because of a traffic accident, his left knee showed obvious swelling. Aspiration of his knee was performed, yielding 70ml of purulent-appearing fluid. To distinguish this condition from purulent or tuberculosis arthritis, arthroscopic biopsy and debridement were performed. Arthroscopic examination visualized distinctive yellow-white soft lesions covering much of the joint capsule, resembling a cobweb. Tissue cultures for bacteria were negative. Pathologically, we identified clusters of xanthoma cells with fibrin exudation due to disruption of the synovium and intra-articular fat pad necrosis. Centrifuging the aspiration fluid yielded a thick creamy lipid layer as the supernatant. A fresh drop preparation showed that the specimen contained innumerable fat globules, which stained red with oil red O stain. The patient was able to walk without difficulty or further swelling of his knee at the end of the second postoperative week. Posttraumatic chylous effusion is self-limited. Purulent arthritis or tuberculosis arthritis, however, should still be the presumptive diagnosis in such cases. Arthroscopic irrigation and debridement should be considered for these traumatic cases to confirm diagnosis and to speed up recovery.

Objective assessments of medial osteoarthritic knee severity by MRI: new computer software to evaluate femoral condyle contours.

An irregular contour of the medial femoral condyle (MFC) on magnetic resonance imaging (MRI) appears to indicate the severity of medial-type knee osteoarthritis (OA). The purpose of this study was to establish a system to enable objective assessments of OA knee severity using newly developed software that semi-automatically measures irregularity of the MFC. (1) We evaluated 48 patients aged 50-83 years with 55 knees of medial-type OA. The following scores were recorded: Lysholm score, visual analogue scale (VAS) and the Japanese Knee Osteoarthritis Measure (JKOM). MFC irregularity was automatically calculated by newly programmed computer software. Four parameters for condyle irregularity were calculated: (a) the average thickness of the contour (ATC), (b) the ratio of the upper surface length to the lower surface length of the contour (RUL), (c) average squared thickness of the contour (ASTC) and (d) standard deviation of the contour thickness (SDC). (2) Nine knees that underwent total knee arthroplasty were further analysed histopathologically and compared with irregularity score. Statistically, the RUL and SDC were significantly correlated with the Lysholm score, VAS and JKOM, with good reliability. Histological examinations showed that an irregular contour reflected the density of cystic lesions formed in subchondral bone. An irregularity of MFC on MRI is correlated with OA disease severity clinically and histopathologically. The new computer software is useful to objectively assess OA disease severity.

RGD peptide-induced cell death of chondrocytes and synovial cells.

BACKGROUND: Small peptides including the Arg-Gly-Asp (RGD) motif have been used in studies on cell-extracellular matrix (ECM) attachment due to their ability to disturb integrin-mediated attachment on the cell surface. As another biological action of RGD peptides, several reports have shown that RGD peptides are incorporated into cytoplasm and induce apoptosis by direct activation of caspase-3. This study evaluated the effect of RGD peptides on chondrocytes and synovial cells and studied the involvement of caspases. METHODS: Chondrocytes and synovial cells were isolated and cultured from the knee joints of New Zealand White rabbits. Cells were incubated in serum-free medium with peptides (RGD, RGDS, GRGDSP, GRGDNP, RGES), and the survival rates were evaluated. The rate of apoptotic cells was measured by flow cytometry in cells treated with RGDS, GRGDSP, and RGES. Caspase-3, -8 and -9 activity was measured in cells treated with RGDS and GRGDSP. Osteochondral explants harvested from rabbits were also incubated with RGD peptides (RGDS, GRGDSP, and GRGDNP), and the survival rate of chondrocytes was evaluated. RESULTS: The survival rate of cultured chondrocytes was significantly decreased in the GRGDSP- and GRGDNP-treated groups. The survival rate of synovial cells was significantly decreased with four of the RGD peptides (RGD, RGDS, GRGDSP, and GRGDNP) at 5 mM, and in the RGDS- and GRGDSP-treated groups at 1 mM. Flow cytometric assay revealed increases of apoptotic chondrocytes with GRGDSP and increases of apoptotic synovial cells with RGDS and GRGDSP. Caspase-3 was activated in chondrocytes treated with GRGDSP and it was also activated in synovial cells treated with RGDS and GRGDSP. Caspases-8 and -9 were not activated in chondrocytes or in synovial cells. The survival rate of chondrocytes in explants decreased in the superficial layer with all three RGD peptides (RGDS, GRGDSP, and GRGDNP) and in the middle layer with GRGDSP. CONCLUSIONS: RGD peptides induced apoptosis in cultured chondrocytes as well as in cells in cartilage explants and synovial cells, presumably through direct activation of caspase-3.

Systematic evaluation of nitric oxide, tetrahydrobiopterin, and anandamide levels in a porcine model of endotoxemia.

PURPOSE: Using a lipopolysaccharide (LPS)-treated porcine model, we examined: (1) whether nitric oxide (NO), anandamide, and tetrahydrobiopterin (BH4) increased or not in early endotoxic shock; and (2) the location of the major site of production of these molecules, by comparing their concentrations in arteries and the portal and hepatic veins. METHODS: Ten pigs received an infusion of LPS at 1.7 microg x kg(-1)x h(-1) via the portal vein for 240 min. Consecutive changes in systemic hemodynamics, hepatosplanchnic circulation, and oxygen delivery were measured. Furthermore, the variable changes in the concentrations of nitrite and nitrate (NOx), anandamide, and BH4 were measured. To access the effects of surgery, anesthesia, and fluid management on BH4, an experiment without LPS infusion was performed in two other animals. RESULTS: Mean arterial pressure and cardiac index started to decrease at 60 min after LPS infusion. However, systemic vascular resistance remained unchanged. Total hepatic blood flow and hepatic oxygen delivery also decreased significantly. NOx and anandamide did not change during LPS infusion. BH4 values did not change without LPS infusion. However, BH4 values increased significantly in the arterial, portal, and hepatic circulation during LPS infusion, especially in the hepatic vein (from 136.8 +/- 27.5 to 281.3 +/- 123.2 mol/ml; P < 0.01). CONCLUSION: Our data suggest that the BH4 values were significantly increased in several organs, especially in the liver during endotoxic shock. Impaired cardiac output and decreased blood pressure appeared in the early phase of porcine endotoxemia. Longer-term observation of these parameters after LPS treatment should be performed as the next step in future studies.

Identification of Pip4k2beta as a mechanical stimulus responsive gene and its expression during musculoskeletal tissue healing.

To investigate the mechano-transduction system of cells, we identified genes responsive to a cyclic mechanical stimulus. MC3T3.E1 cells were cultured on a computer-controlled vacuum-pump-operated device designed to provide a cyclic mechanical stimulus. A maximum elongation of 15% of membrane at 10 cycles/min (3 s extension followed by 3 s relax per cycle) was repeated for 48 h. By means of a differential display, the gene expression pattern of cells exposed to the stimulus was compared with that of unexposed cells. As a result, a gene fragment that was exclusively expressed in mechanically stressed cells was identified. By using expressed sequence tag walking together with the oligo-capping method, this gene was identified as phosphatidylinositol 4-phosphate 5-kinase type II beta (initially known as Pip5k2beta but now reclassified as Pip4k2beta). The specific up-regulation of Pip4k2beta upon mechanical stimulus was also confirmed by using another apparatus, viz. a computer-controlled linearized-stepping motor system. To examine the involvement of the cyclic mechanical stimulus in the regulation of Pip4k2beta expression in musculoskeletal tissue, we created an Achilles tendon transection model in rabbits. The temporal expression of Pip4k2beta was assessed by means of a quantitative reverse-transcribed polymerase chain reaction. In the gastrocnemius muscle, expression of Pip4k2beta rapidly decreased 1 week after transection but was restored to normal levels at 4 weeks. In the Achilles tendon, however, expression remained decreased until 4 weeks after transection. We suggest that the expression of Pip4k2beta can be used as a marker for cells receiving a suitable mechanical stimulus.

Effects of olprinone on hepatosplanchnic circulation and mitochondrial oxidation in a porcine model of endotoxemia.

PURPOSE: This study was performed in order to assess the effects of olprinone, a phosphodiesterase III inhibitor, on hepatic oxygen delivery (DO2H), oxygen consumption (VO2H), and mitochondrial oxidation in the liver of a porcine endotoxemia model. METHODS: Fourteen pigs received continuous infusion of endotoxin via the portal vein for 240 min. From t = 150 to t = 240 min, animals were randomly divided into two groups to receive saline (control [CONT]; n = 7), or olprinone (OLP; n = 7) via the central vein. RESULTS: In the OLP group, prior to olprinone treatment at 150 min, endotoxin induced significant decreases in the cardiac index (CI; from 120 +/- 31 to 65 +/- 13 ml.kg(-1).min(-1); P < 0.01) and DO2H (from 3.58 +/- 0.81 to 1.55 +/- 0.49 ml.kg(-1).min(-1); P < 0.01), while VO2H was maintained. After administration of olprinone (from t = 150 to t = 240 min), CI was unchanged, while DO2H increased from 1.55 +/- 0.49 to 1.93 +/- 0.38 ml.kg(-1).min(-1) (P < 0.01) and VO(2)H increased from 0.42 +/- 0.28 to 0.69 +/- 0.38 ml.kg(-1).min(-1) (P < 0.01). At t = 240 min, the oxidation level of cytochrome aa3 was significantly higher in the OLP group than in the CONT group (OLP, 66.2 +/- 19.3% vs CONT, 26.4 +/- 17.3%; P < 0.01). CONCLUSION: Our data for this porcine endotoxemia model suggest that olprinone may have beneficial therapeutic effects in restoring not only systemic and hepatic circulation but also mitochondrial oxidation in the liver.

The extent of ossification of posterior longitudinal ligament of the spine associated with nucleotide pyrophosphatase gene and leptin receptor gene polymorphisms.

STUDY DESIGN: A case-control study using radiograph findings and the PCR assay with regard to the susceptibility and the severity of ossification of posterior longitudinal ligament of the spine (OPLL). OBJECTIVE: To analyze whether polymorphisms of the nucleotide pyrophosphatase (NPPS) gene and the leptin receptor gene predispose to an increased frequency and severity of OPLL. SUMMARY OF BACKGROUND DATA: The NPPS gene is responsible for ectopic ossification in the ttw mouse, an animal model for OPLL. The Zucker fatty rat, another animal model for OPLL, has a missense mutation in the leptin receptor gene. METHODS: Analysis of 172 OPLL patients and 93 non-OPLL controls was performed. Radiographs of the cervical, thoracic and lumber spine were analyzed to determine whether OPLL was present and to what degree. Genomic DNA was extracted from all participants. Polymorphisms of the NPPS gene and the leptin receptor gene were analyzed using the PCR assay. The association of the polymorphisms with the development and extent of OPLL were statistically evaluated. RESULTS: No significant association was found between the polymorphisms and the existence of OPLL in both the NPPS and the leptin receptor genes. However, the IVS20-11delT variant in the NPPS gene and the A861G variant in the leptin receptor gene were more frequent in patients with OPLL in the thoracic spine compared with patients whose OPLL was restricted to the cervical spine. CONCLUSION: The present results suggest that the IVS20-11delT variant of the NPPS gene and the A861G variant of the leptin receptor gene are associated with more extensive OPLL, but not with the frequency with which it occurs.