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Case A 49-year-old woman injured her anterior cruciate ligament (ACL) as a high-school student. Double-bundle ACL reconstruction (DBACLR) using hamstring tendon grafts was performed because of recurrent instability. Eleven years after DBACLR, total knee arthroplasty was performed because of osteoarthritis progression. Histologic analysis was completed to observe the osteointegration of the tendon in the obtained proximal tibia. The tibial tunnel showed Sharpey-like fibers anteriorly, connecting the tendon graft and lamellar bone, whereas the intraarticular exit revealed well-aligned chondrocytes posteriorly, indicating chondral metaplasia of the tendon graft. Conclusion Tendon-bone healing can regenerate both fibrous insertion and chondral metaplasia in DBACLR.

Metals have been used clinically as biomaterials, especially in the orthopaedic and dental fields. Metals used as implants wear at contact surfaces, producing metal particles and metal ions that may be harmful. Newly developed metal implants and methods of implant surface modification are currently under scrutiny. We evaluated the use of electrolytic in-process dressing (ELID) as a surface finishing method for metal implants. Metal implants processed using the ELID method (ELID group) or not processed (Non-ELID group) were inserted surgically into rabbit femurs. The rabbits were sacrificed postoperatively over a 24-week period. We assessed the concentrations of the cytokines, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, the resistance to implant pull-out, and histopathology at the implant site. There was no significant difference between the groups regarding the cytokine concentrations or implant pull-out resistance. Many particles indicating wear around the implant were noted in the Non-ELID group (n=10) but not the ELID group (n=13), while a fibrous membrane adhering to the every implant was noted in the ELID group. The formation of a fibrous membrane rather than metal particles in the ELID group may indicate improved biocompatibility, and it suggests that ELID may prevent corrosion in the areas of contact.

Venous thromboembolism (VTE) is a potential complication occurring after total knee arthroplasty (TKA). We investigated the incidence of VTE after TKA using contrast-enhanced computed tomography (CT), and assessed the efficacy of VTE prophylaxis (fondaparinux and enoxaparin). At our hospital, 189 patients (225 knees) underwent TKA between April 2007 and October 2011. The 225 knees were divided into a control group with no VTE prophylaxis (31 cases), a fondaparinux group (107 cases), and an enoxaparin group (87 cases). Contrast-enhanced CT screening for VTE was performed in all cases on day 5 or 6 after TKA. D-dimer levels were measured on day 5 after TKA, and were significantly lower in the fondaparinux (9.8 ± 3.8) and enoxaparin groups (9.4 ± 4.9) than in the control group (15.6 ± 9.8) (p ＜ 0.001). However, no statistically significant difference in the incidence of VTE was observed among the groups (control, 61.3%;fondaparinux, 49.5%;enoxaparin, 50.6%). Prophylaxis was not effective for the prevention of VTE as detected by contrast-enhanced CT after TKA. CT should be performed after TKA, even when VTE prophylaxis is used.

The purpose of this study was to investigate the incidence of cyclops lesions and its relationship with the cross-sectional area of the intercondylar notch.For this study, 55 patients (24 male and 31 female) underwent follow-up arthroscopy after bi-socket anterior cruciate ligament reconstruction with hamstring tendon grafts were included. All patients underwent magnetic resonance imaging measurements of intercondylar notch dimensions. We compared the femoral intercondylar notch sizes and bone tunnel sizes between knees with cyclops lesions (cyclops group) and those without cyclops lesions (no-cyclops group). The mean percentage of the tunnel size to the cross-sectional area of the femoral intercondylar notch was also compared between the groups. The median follow-up duration was 3.8 years.Cyclops lesions were found in 15 of the 55 knees (27.3 %) on second-look arthroscopy (cyclops group). Only 6 of the 55 knees (10.9 %) had extension loss (cyclops syndrome). The cyclops group included 3 men and 12 women. The two groups showed a statistical difference in sex variation (P = 0.04). No significant differences were found in the femoral and tibial tunnel sizes between the two groups. The cross-sectional area of the femoral intercondylar notch was significantly smaller in the cyclops group (251.7 ± 63.2 mm(2)) than in the no-cyclops group (335.6 ± 77.6 mm(2)) (P 0.001). The percentage of the total femoral tunnel size to the cross-sectional area of the femoral intercondylar notch was significantly higher in the cyclops group (18.6 ± 5.3 %) than in the no-cyclops group (13.2 ± 3.6 %) (P = 0.02).A smaller intercondylar notch size may be a potential risk factor for cyclops lesion formation.Case-control study, Level IV.

A surf zone with large breaking waves produces more spray than do offshore regions. Latent heat of spray evaporation causes change in the surrounding temperature and wind velocity, resulting in further alterations in temperature, wind velocity and heat flux. Spray in a surf zone with large breaking waves may have unignorable effect on determination of a local meteorological field because of this interconnected relationship as well as its higher population than in the open ocean. In this study, the effects of the spray latent heat on a meteorological field were investigated. The authors propose a method for estimating latent heat of spray vaporization over the ocean. The method was applied to a meso-scale meteorological model to perform numerical experiments with consideration of heat flux by spray. Although the contribution of heat flux on the ocean was as small as 2.5%, fluctuations of air temperature and wind velocity increased over time due to the effects of spray. The fluctuations are thought to cause uncertainty in weather prediction. Numerical experiments with spray provided predictions of air temperature and wind velocity near a coast line that were consistent with observational data, especially when the population of spray droplets increased by two orders of magnitude as is often observed in a coastal area.

Bone marrow-stimulating techniques such as microfracture and subchondral drilling are valuable treatments for full-thickness cartilage defects. However, marrow stimulation-derived reparative tissues are not histologically well-documented in human osteoarthritis. We retrospectively investigated cartilage repairs after marrow stimulation for the treatment of large cartilage defects in osteoarthritic knees. Tissues were obtained from patients who underwent total knee arthroplasty (TKA) after arthroscopic marrow stimulation in medial compartmental osteoarthritis. Clinical findings and cartilage repair were assessed. Sections of medial femoral condyles were histologically investigated by safranin O staining and anti-type II collagen antibody. Marrow stimulation decreased the knee pain in the short term. However, varus leg alignment gradually progressed, and TKA conversions were required. The grade of cartilage repair was not improved. Marrow stimulations resulted in insufficient cartilage regeneration on medial femoral condyles. Safranin O-stained proteoglycans and type II collagen were observed in the deep zone of marrow-stimulated holes. This study demonstrated that marrow stimulation resulted in failed cartilage repair for the treatment of large cartilage defects in osteoarthritic knees. Our results suggest that arthroscopic marrow stimulation might not improve clinical symptoms for the long term in patients suffering large osteoarthritic cartilage defects.

The purpose of this paper is to prove the reliability of artificial hip joints’ surface generated by the electrolytically treated grinding process; the evaluation was carried out in a hip simulator and animal tests. The evaluation indicated that the fabricated hyper-hemispherical shaped artificial hip joints presented a high quality smoother surface than 10 nm in Ra. The fabricated surface also showed its ability to prevent crystalline phase transition during the hip simulation test, suggesting that the stably modified layer was generated via grinding process. The results of animal test showed that the fabricated surface could have a highly-improved biocompatibility.

The meniscus is a fibrocartilaginous tissue that plays an important role in controlling complex biomechanics of the knee. A perimeniscal capillary plexus supplies the outer meniscus, whereas the inner meniscus is composed of avascular tissue. Anti-angiogenic molecules, such as chondromodulin-I (ChM-I) and endostatin, have pivotal roles in preserving the avascularity of cartilage. However, the anti-angiogenic role of ChM-I is unclear in the meniscus. We hypothesized that the inner meniscus might maintain its avascular feature by expressing ChM-I. Immunohistochemical analyses revealed that ChM-I was mainly detected in the inner and superficial zones of the meniscus. On the other hand, endostatin distribution was similar between the inner and outer meniscus. In Western blot, ChM-I was detected only in the inner meniscus, whereas endostatin was equally observed in both inner and outer menisci. In addition, ChM-I concentration of the inner meniscus-derived conditioned medium was higher than that of the outer meniscus-derived medium. ChM-I removal from the inner meniscus-derived medium and functional blocking of ChM-I significantly increased endothelial cell proliferation. In this study, we demonstrated that the inner meniscus contained larger amounts of ChM-I, and that the inner meniscus-derived ChM-I inhibited endothelial cell proliferation. Our results suggest that ChM-I may be a key anti-angiogenic factor for maintaining the avascularity of the inner meniscus.

Toolpath generation for a multi-axis medical machine tool is a challenging task. In surgical procedures, it is difficult to apply industrial CAM technology owing to the requirement for quick toolpath generation and the likelihood of tool interference with complex structures of the target area. The objectives of this study are to optimize the initial position and posture of the cutting tool for performing the ideal skin incision and to minimize contact between the cutting tool and the surrounding area. We propose a novel toolpath strategy based on geometric models. It can be potentially applied to general machine-assisted surgeries.

Basic fibroblast growth factor (bFGF) and growth and differentiation factor (GDF)-5 stimulate the healing of medial collateral ligament (MCL) injury. However, the effect of isolated and combined use of bFGF/GDF-5 remains still unclear. We investigated cellular proliferation and migration responding to bFGF/GDF-5 using rabbit MCL fibroblasts. Rabbit MCL injury was treated by bFGF and/or GDF-5 with peptide hydrogels. Gene expression and deposition of collagens in healing tissues were evaluated. bFGF/GDF-5 treatment additively enhanced cell proliferation and migration. bFGF/GDF-5 hydrogels stimulated Col1a1 expression without increasing Col3a1 expression. Combined use of bFGF/GDF-5 stimulated type I collagen deposition and the reorganization of fiber alignment, and induced better morphology of fibroblasts in healing MCLs. Our study indicates that combined use of bFGF/GDF-5 might enhance MCL healing by increasing proliferation and migration of MCL fibroblasts, and by regulating collagen synthesis and connective fiber alignment.

Biomechanical stimuli have fundamental roles in the maintenance and remodeling of ligaments including collagen gene expressions. Mechanical stretching signals are mainly transduced by cell adhesion molecules such as integrins. However, the relationships between stress-induced collagen expressions and integrin-mediated cellular behaviors are still unclear in anterior cruciate ligament cells. Here, we focused on the stretch-related responses of different cells derived from the ligament-to-bone interface and midsubstance regions of human anterior cruciate ligaments. Chondroblastic interface cells easily lost their potential to produce collagen genes in non-stretched conditions, rather than fibroblastic midsubstance cells. Uni-axial mechanical stretches increased the type I collagen gene expression of interface and midsubstance cells up to 14- and 6-fold levels of each non-stretched control, respectively. Mechanical stretches also activated the stress fiber formation by shifting the distribution of integrin alphaVbeta3 to the peripheral edges in both interface and midsubstance cells. In addition, integrin alphaVbeta3 colocalized with phosphorylated focal adhesion kinase in stretched cells. Functional blocking analyses using anti-integrin antibodies revealed that the stretch-activated collagen gene expressions on fibronectin were dependent on integrin alphaVbeta3-mediated cellular adhesions in the interface and midsubstance cells. These findings suggest that the integrin alphaVbeta3-mediated stretch signal transduction might have a key role to stimulate collagen gene expression in human anterior cruciate ligament, especially in the ligament-to-bone interface.

Cellular activities responding to growth factors are important in ligament healing. The anterior cruciate ligament (ACL) has poor healing potential compared to the medial collateral ligament (MCL). To assess the differences, we investigated the proliferation, migration, adhesion, and matrix synthesis responding to growth factors in rabbit ACL and MCL fibroblasts. ACL cell proliferation to basic fibroblast growth factor (bFGF), bone morphogenetic protein-2, growth and differentiation factor (GDF)-5, and GDF-7 treatment was similar to that of MCL cells. GDF-5 enhanced Col1a1 expression in ACL and MCL fibroblasts up to 4.7- and 17-fold levels of control, respectively. MCL fibroblasts showed stronger migration activities in response to bFGF and GDF-5 than ACL cells. GDF-5/7 and bFGF also changed the stress fiber formation and cellular adhesion by modulating the distribution of integrin alpha2. Functional blocking analyses using anti-integrin alpha2 antibodies revealed that cellular migration responding to growth factors depended on the integrin alpha2-mediated adhesion on type I collagen. The expression of integrin alpha2 was also increased by growth factors in both cells. Our results demonstrate that GDF-5/7 and bFGF stimulate cellular migration by modulating integrin alpha2 expression and integrin alpha2-dependent adhesion, especially in MCL fibroblasts. These findings suggest that the different healing potential between ACL and MCL may be caused by different cellular behavior in the integrin alpha2-mediated cellular migration in response to growth factors.

Optimal control of the machining process in orthopedic surgery can not only increase productivity but also ensure safety during tool usage. The authors have developed a technology for a force control system. The system has two modes of operation: the “air-cutting mode” and the “force control mode.” In the air-cutting mode, tool feed is scheduled by predicting the air and bone-cutting zones from the CAD/CAM system. In the force control mode, the software monitors the cutting force and the cutting temperature, and it controls the feed override according to the difference between the real and the desired cutting force. The software is installed on a robot controller, and its effectiveness is evaluated with a urethane bone.

We prospectively evaluated the disease-specific features of the early postoperative plasma D: -dimer value and the relationship with deep venous thrombosis and/or pulmonary thromboembolism (DVT/PE) in 95 patients following total knee arthroplasty. Patients in whom DVT/PE was highly suspected were diagnosed by high-resolution multi-detector row computed tomography scanning (MDCT). Forty-nine knees in 46 patients with rheumatoid arthritis (RA, 24 knees) or osteoarthritis (OA, 25 knees) were finally recruited. DVT/PE was detected in 28 (57.1%) of the 49 cases examined by diagnostic MDCT: 12 (50.0%) of the 24 cases of RA, and 16 (64.0%) of the 25 cases of OA. Of these, PE was found in 11 cases (39.2%), but none of them showed clinical symptomatic signs of dyspnea or chest pain. In both RA and OA cases, there were statistically significant differences in the D: -dimer value on postoperative day 3 (P = 0.027) and after day 28 (P = 0.037) between the groups with and without DVT/PE. In OA cases, there were significant differences between the two groups on postoperative days 1 (P = 0.034), 3 (P = 0.020), 5 (P = 0.005), and 7 (P = 0.045), respectively. At the baseline, perioperative D: -dimer levels in the RA group without DVT/PE were higher than in the OA group. However, multivariate logistic regression analysis showed that RA was not a significant risk factor of DVT/PE in comparison with OA. In conclusion, individual evaluation of the D: -dimer level between RA and OA should provide a more precise predictive indicator of early postoperative DVT/PE.

To differentiate benign from malignant bone tumors by analyzing the vascular distribution within bone tumors with dynamic contrast-enhanced MRI.We studied dynamic contrast-enhanced MRI for 49 bone tumors (22 malignant and 27 benign tumors). Seven small regions of interest (ROI) were set inside the largest portion of each tumor. Four ROI were placed evenly on the periphery and three ROI were placed evenly on the line of the longest breadth within the tumor. The slope of the curve (%Slope) was calculated on the time-intensity curves of the whole tumor and of each ROI. The variance values for the %Slope of the ROI were calculated to assess the dispersion of the intensity change at each ROI within the tumor.Mean value of the %Slopes of whole tumor regions for malignant bone tumors (70.4 +/- 60.3%) was significantly higher than that for benign bone tumors (37.6 +/- 52.9%) (P = 0.015), although giant cell tumor (GCT), a locally aggressive tumor, had a relatively higher %Slope. Mean value of the variance of %Slopes for malignant bone tumors (3485.9 +/- 5942.5) was significantly higher than that for all benign tumors (470.4 +/- 583.9) (P = 0.012), indicating that the %Slope values of seven ROI within malignant bone tumors varied more widely compared with the ROI inside benign bone tumors. GCT also demonstrated a lower value.Our method of analyzing the signal intensity change at seven separate regions that evaluates the vascular distribution within a tumor could be a useful tool for differentiating between benign and malignant bone tumors.

In successful knee arthroplasty, the femur and the tibia must be shaped to fit an artificial joint. The recent trend towards MIS (Minimally Invasive Surgery) to decrease the length of the required incision in the skin has increased surgical difficulty, since the open access area is small. The developed system consists of (1) a preplanning system providing a CAD function, (2) a multi-axis CAM system which avoids cutting the skin and the ligament, and keeps the cutting time within acceptable limits, and (3) a 7-axis machine tool that assures the safety of the patient and the surgeon, and enables MIS.

Bone cutting experiments were conducted on a cadaver using a newly developed machine tool. The effectiveness of the system was evaluated by comparing the planned shape for the mating surface between the femur and an artificial joint with the cutting result. It is desirable to know the machining phenomena and characteristics at the microscale because the material and the tissue structure are anisotropic in both cortical and cancellous bones. In the paper, the influence of the material characteristics on machining is discussed for cortical bone. Pig cortical bone was used in the experiment for visualizing 2-dimensional micro-cutting.

Regional gene therapy, which involves the delivery of growth factors to a specific anatomic site, has the potential to enhance bone formation in clinical application. Helper-dependent adenoviral vectors, which have deleted all of the viral coding regions, have been shown to be safe and highly efficient with long-lasting transgene expression. In this study, we constructed a helper-dependent adenoviral vector producing bone morphogenetic protein-2 (AdHDBMP-2). The AdHDBMP-2 increased the alkaline phosphatase activity of W-20-17 cells in vitro. In addition, when AdHDBMP-2 infected rat bone marrow cells were implanted into the hindlimbs of SCID mice, orthotopic bone formation was shown at 2 weeks. To our knowledge, this is the first study to demonstrate bone formation with the helper-dependent adenoviral vector with the BMP-2 expression cassette. This type of gene therapy vector could prove to be highly useful for bone augmentation in patients with bone loss associated with trauma, revision total joint arthroplasty, or cancer.

Novel benzamide derivatives, N-[1-(aminocarbonyl)-2-(1-piperidinyl)ethyl]benzamides (4 and 5), were prepared from the reaction of beta-piperidinoalanine (6) as the starting material.

We measured the cross-sectional area (CSA) of the semitendinosus tendon (SMT) in 79 anterior cruciate ligament (ACL)-injured patients using magnetic resonance imaging (MRI) to scrutinize their appropriateness for ACL grafts. Measurements of the CSAs of the SMT with MRI were closely correlated with intraoperative direct measurement (y = 0.697). The mean CSAs of the SMT measured with MRI ranged from 6.3 to 15.0 mm2 with a mean of 10.1+/-2.1 mm2. The CSA of the SMT measured with MRI proved to be a useful indicator to determine preoperatively whether the SMT graft would be of adequate dimensions (7 mm or more in diameter, 60 mm or more in length) for ACL reconstruction. If the CSA of the SMT was more than 11 mm2, a sufficiently thick and long graft could be prepared with a tripled or quadrupled SMT in 89% of cases. We conclude that tissue CSA measurements using MRI could potentially be implemented as a useful tool for determining the most appropriate donor autograft tissue preoperatively, thus minimizing harvest-site morbidity.

Clinical and radiographic studies were performed on 228 hips of 145 patients with avascular necrosis of the femoral head (ANFH). The patients were divided into three groups: group A consisted of 33 patients with systemic lupus erythematosus (SLE) who had been treated with systemic corticosteroids (59 hips); group B consisted of 41 patients with a history of corticosteroid treatment, excluding patients with SLE (69 hips); and group C consisted of 71 patients with no history of corticosteroid use (100 hips). Of the 228 hips, 80 hips at an early stage of the necrosis, but not showing collapse, were selected and classified by the criteria of the Japanese Investigation Committee (JIC) to define the natural history of the disease. In the SLE patients (group A), there was a predisposition to bilateral involvement and multiple sites of bone necrosis. Eighty percent of the femoral heads followed at an early stage had collapsed at the end of the follow-up, the incidence of collapse in group A being higher than that in the other groups. The collapses in group A were predominantly types 1C, 2, and 3B according to the JIC criteria. The incidence of collapse was significantly lower in type 1A and type 3A than in the other types. The classification proposed by the JIC, in terms of types with regard to size and location of the necrotic area on antero-posterior radiographs, was very useful for evaluation of the risk of collapse as well as for selecting appropriate treatment modalities, either conservative or surgical, during the early stages of ANFH.

The meniscus is a fibrocartilaginous tissue that plays an important role in controlling complex biomechanics of the knee. A perimeniscal capillary plexus supplies the outer meniscus, whereas the inner meniscus is composed of avascular tissue. Anti-angiogenic molecules, such as chondromodulin-I (ChM-I) and endostatin, have pivotal roles in preserving the avascularity of cartilage. However, the anti-angiogenic role of ChM-I is unclear in the meniscus. We hypothesized that the inner meniscus might maintain its avascular feature by expressing ChM-I. Immunohistochemical analyses revealed that ChM-I was mainly detected in the inner and superficial zones of the meniscus. On the other hand, endostatin distribution was similar between the inner and outer meniscus. In Western blot, ChM-I was detected only in the inner meniscus, whereas endostatin was equally observed in both inner and outer menisci. In addition, ChM-I concentration of the inner meniscus-derived conditioned medium was higher than that of the outer meniscus-derived medium. ChM-I removal from the inner meniscus-derived medium and functional blocking of ChM-I significantly increased endothelial cell proliferation. In this study, we demonstrated that the inner meniscus contained larger amounts of ChM-I, and that the inner meniscus-derived ChM-I inhibited endothelial cell proliferation. Our results suggest that ChM-I may be a key anti-angiogenic factor for maintaining the avascularity of the inner meniscus.

We have cloned and characterized cDNAs encoding the alpha 1 chain of type XV collagen from a human placenta library. Using primer extension cloning we extended the cDNAs to the 5' end of the mRNA and determined the complete deduced primary structure of the human alpha 1(XV) chain. The polypeptide chain contains nine triple helical domains separated by eight non-triple helical regions and flanked by large amino-terminal (555 amino acid residues) and carboxyl-terminal (256 amino acid residues) non-triple helical domains. Comparison of amino acid sequences of the human alpha 1(XV) chain with those of mouse alpha 1(XVIII) collagen showed remarkable similarity within both amino- and carboxyl-terminal non-triple helical domains. Within the carboxyl third of the amino-terminal domain a tandem repeat structure is found with an about 45-amino acid residue sequence repeated four times. This amino acid sequence has a strikingly high similarity to rat cartilage proteoglycan core protein. Northern blot analysis of human embryonic RNA revealed that alpha 1(XV) mRNA is expressed predominantly in internal organs such as the adrenal gland, kidney, and pancreas.

Type IX collagen is a newly discovered collagen molecule that is associated with Type II-containing collagen fibrils in cartilage, vitreous and embryonic cornea. It consists of three distinct chains: alpha 1(IX), alpha 2(IX) and alpha 3(IX). The alpha 1(IX) chain has been to be synthesized in two different forms, which are generated by alternative transcription and splicing. In this manuscript we describe the isolation and sequencing of a cDNA coding for the entire coding region of the long form of mouse alpha 1(IX) chain. Nucleotide sequence analysis of this cDNA determined for the first time the primary structure of the entire long form of the mouse alpha 1(IX) chain. RT-PCR was used to examine collagen gene expression during limb development from day 10 to 18 in mouse embryos. Collagen I and II mRNA levels gradually increased all through the developmental stages. Collagen X expression increased further after day 16 in limb development, whereas the alpha 1(IX)mRNA level dropped at this time. This could be due to active bone formation relative to cartilage synthesis in the embryonic limb bud around day 16 in mouse development.

Loose fragments in spontaneous osteonecrosis of the knee (SONK) are usually removed by surgical treatment. However, the healing potential of osteonecrotic loose fragments and their clinical availability, for example as a cell source for cartilage repair and tissue engineering, have not been investigated. The objective of this study was to evaluate the cellular proliferation and redifferentiation ability of loose fragment chondrocytes for the treatment of SONK.Cells were obtained from the remaining cartilage of chondral loose fragments or fibrocartilaginous tissue under the affected femoral condyle in SONK. The proliferation activity of loose fragment-derived chondrocytes and condyle-derived fibrochondrocytes was evaluated. In-vitro differentiation ability was assessed by PCR and histological analysis.The deposition of proteoglycans and type II collagen were maintained in loose fragments. However, loose fragment-derived chondrocytes had lower proliferating activity than condyle-derived fibrochondrocytes. Chondrogenic redifferentiation ability was lower in loose fragment chondrocytes than in condyle fibrochondrocytes. Differentiation towards adipogenic and osteogenic lineages was not observed in loose fragment chondrocytes. On the other hand, lipid vacuoles were detected in fibrochondrocytes after adipogenic treatment.This study demonstrated that loose fragment-derived chondrocytes in SONK had lower potential than fibrochondrocytes in cellular proliferation and redifferentiation. Our experimental results suggest that osteonecrotic loose fragments might have restricted cellular properties in the healing of SONK-related osteochondral defects.

We have isolated mouse cDNA clones that encode a newly discovered collagenous polypeptide. Four overlapping cDNA clones contained an open reading frame of 1140 amino acid residues of collagenous and non-collagenous domains. The predicted polypeptide consists of 10 collagenous domains of various length that are interrupted by 11 noncollagenous domains. The overall structural arrangement differed significantly from reported collagen chains of 17 different types. Northern-blot analyses showed hybridization of the cDNA to 5.6kb and 4.8kb mRNA species in liver and kidney that are due to utilization of the two poly (A) signals.

Tool interference causes serious damage to surrounding soft tissue in minimally invasive orthopedic surgery with a milling robot. The objective of this study is to avoid the collision of cutting tool with complicated shapes, and a novel approach of interference-free toolpath generation in a short intraoperative time is proposed. In order to resolve this issue, we propose the following two methods: intraoperative modeling of soft tissues as an interference area and interference-free toolpath generation based on the model. A model is constructed to represent the opening area and the internal tissues by using a 3-dimensional optical position sensor to measure them. Based on the constructed model, interference-free toolpath is immediately determined by the preliminary definition of evacuating direction. The effectiveness of the proposed method is evaluated with artificial models on the system that the authors have developed so far. A tool contact force against the model was measured by a force sensor mounted on the cutting tool. The result revealed that the tool interference was greatly reduced by implementing the proposed method.

For the total knee arthroplasty, we developed the robotic system, such as the cutting feed rate is controlled depending on the hardness of the bone tissue predicted on the basis of the medical image. Since the cutting force is reduced by this system, the displacement of the bone is minimized during the bone cutting process. Therefore it makes a possibility to fix the target bone using “safer” and less-invasive fixation technique.

Novel benzamide derivatives, N-[1-(aminocarbonyl)-2-(1-piperidinyl)ethyl]benzamides (4 and 5), were prepared from the reaction of β-piperidinoalanine (6) as the starting material.

Cellular activities responding to growth factors are important in ligament healing. The anterior cruciate ligament (ACL) has poor healing potential compared to the medial collateral ligament (MCL). To assess the differences, we investigated the proliferation, migration, adhesion, and matrix synthesis responding to growth factors in rabbit ACL and MCL fibroblasts. ACL cell proliferation to basic fibroblast growth factor (bFGF), bone morphogenetic protein-2, growth and differentiation factor (GDF)-5, and GDF-7 treatment was similar to that of MCL cells. GDF-5 enhanced Col1a1 expression in ACL and MCL fibroblasts up to 4.7- and 17-fold levels of control, respectively. MCL fibroblasts showed stronger migration activities in response to bFGF and GDF-5 than ACL cells. GDF-5/7 and bFGF also changed the stress fiber formation and cellular adhesion by modulating the distribution of integrin alpha2. Functional blocking analyses using anti-integrin alpha2 antibodies revealed that cellular migration responding to growth factors depended on the integrin alpha2-mediated adhesion on type I collagen. The expression of integrin alpha2 was also increased by growth factors in both cells. Our results demonstrate that GDF-5/7 and bFGF stimulate cellular migration by modulating integrin alpha2 expression and integrin alpha2-dependent adhesion, especially in MCL fibroblasts. These findings suggest that the different healing potential between ACL and MCL may be caused by different cellular behavior in the integrin alpha2-mediated cellular migration in response to growth factors.

The reductions of an α, β-unsaturated lactone (5) and lactam (7) with the Ni2+/BH-4 system resulted in the formation of cis-hydrogenated products (8a and 9a) with high stereoselectivity. The cis products (8a and 9a) were easily isomerized to the corresponding trans isomers (8b and 9b, respectively) by refluxing with sodium methoxide in anhydrous methanol. Isotope labeling studies with methyl cinnamate as the substrate indicated that the reduction with this reducing system poceeds stepwise via a carbon-nickel intermediate.

New oxazolidin-2-ones (3), which mimic the clinically useful antibacterial agent (1) (Linezolid) were prepared by using a cyclization procedure with diethyl carbonate from aminoalcohol (7) starting with DL-serine methyl ester hydrochloride (4) and aromatic carboxylic acid derivatives (5).

A facile ring transformation of 1, 2, 3, 5, 6, 7-hexahydropyrrolizinium perchlorates (1 and 2) to 1-substituted 5-oxoperhydroazocines (5) is described. The spectroscopic and chemical properties of these products are also presented.

Many of the robots developed so far, including our multi-axis bone cutting robot, use an end mill as the cutting tool, and some problems should be solved to apply them to the minimally invasive orthopedic surgery. Minimally invasive surgery makes the incisions smaller, reduces pain and trauma to the body, and enables faster recovery. The smaller incision means a small and narrow opening area. This means the robot attitude for the bone resection is restricted, and it can result in the collision of the tool with the surrounding tissue, the existence of an untouched area and the degradation of the joint position accuracy. This paper proposes a robot mechanism and a toolpath generation technique specialized for bone cutting is expected to resolve these issues.

Summary Objective To investigate the effect of the histone deacetylase (HDAC) inhibitor, trichostatin A (TSA), on joint inflammation and cartilage degeneration in a collagen antibody-induced arthritis (CAIA) mouse model. Methods CAIA mice were given daily subcutaneous injections of various concentrations of TSA (0, 0.5, 1.0, and 2.0 mg/kg) and various parameters were monitored for 14 days. On Day 15, the hind paws were examined histologically. To investigate the effects of TSA on the expressions of matrix metalloproteinase (MMP)-3, MMP-13, tissue inhibitor of MMP-1 (TIMP-1), and acetyl-H4 by chondrocytes, another group of mice was sacrificed on Day 6. In vitro direct effect of TSA was examined by real-time PCR for mRNA of type II collagen, aggrecan, MMP-3, and MMP-13 in murine chondrogenic ATDC5 cells after pro-inflammatory cytokine stimulation. Results In the TSA-treated group, clinical arthritis was significantly ameliorated in a dose-dependent manner. The severity of synovial inflammation and the cartilage destruction score were significantly lower in the TSA 2.0 mg/kg group compared to the other TSA-treated groups. On immunohistochemistry, the number of MMP-3 and MMP-13-positive chondrocytes was significantly lower in the TSA 2.0 mg/kg group than in the control group. In contrast, the number of TIMP-1-positive cells and acetyl-histone H4-positive cells was significantly higher in the TSA 2.0 mg/kg group than in the control group. TSA suppressed interleukin 1-β and tumor necrosis factor-α-stimulated up-regulation of MMP-3, but not MMP-13 mRNA expression by ATDC5. Conclusion The systemic administration of TSA ameliorated synovial inflammation in CAIA mice. Subsequently cartilage destruction was also suppressed by TSA, at least in part, by modulating chondrocyte gene expression.

Preparation of β-(sec-amino)alanines (3) by acid hydrolysis of diethyl (sec-aminomethyl)formamidomalonates (2) was studied. Although high reaction temperature resulted in low yield, low reaction temperature (below 30°C) gave good to excellent yields. The hydrolysis of diethyl formamido(piperidinomethyl)malonate (2a) was followed by 1H-NMR, and a plausible mechanism involving the condensation of ethyl hydrogen aminomalonate (7) with 1-piperidinemethanol (5) is proposed.