蛍光タンパク導入マウス由来骨芽細胞を用いたアルカリ加熱処理チタンの生体活性能の評価

京都大学0048新制・課程博士博士(医学)甲第18146号医博第3866号新制||医||1002(附属図書館)31004京都大学大学院医学研究科医学専攻(主査)教授 鈴木 茂彦, 教授 妻木 範行, 教授 戸口田 淳也学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Differentiation of hypertrophic chondrocytes from human iPSCs for the in vitro modeling of chondrodysplasias

iPS細胞から肥大軟骨細胞への誘導法を確立し、成長板疾患の病態再現に成功. 京都大学プレスリリース. 2021-02-26.Reprogramming children's cells to study cartilage diseases. 京都大学プレスリリース. 2021-02-26.Chondrodysplasias are hereditary diseases caused by mutations in the components of growth cartilage. Although the unfolded protein response (UPR) has been identified as a key disease mechanism in mouse models, no suitable in vitro system has been reported to analyze the pathology in humans. Here, we developed a three-dimensional culture protocol to differentiate hypertrophic chondrocytes from induced pluripotent stem cells (iPSCs) and examine the phenotype caused by MATN3 and COL10A1 mutations. Intracellular MATN3 or COL10 retention resulted in increased ER stress markers and ER size in most mutants, but activation of the UPR was dependent on the mutation. Transcriptome analysis confirmed a UPR with wide-ranging changes in bone homeostasis, extracellular matrix composition, and lipid metabolism in the MATN3 T120M mutant, which further showed altered cellular morphology in iPSC-derived growth-plate-like structures in vivo. We then applied our in vitro model to drug testing, whereby trimethylamine N-oxide led to a reduction of ER stress and intracellular MATN3

Early migration of a medially stabilized total knee arthroplasty : a radiostereometric analysis study up to two years

Aims Medial pivot (MP) total knee arthroplasties (TKAs) were designed to mimic native knee kinematics with their deep medial congruent fitting of the tibia to the femur almost like a ball-on- socket, and a flat lateral part. GMK Sphere is a novel MP implant. Our primary aim was to study the migration pattern of the tibial tray of this TKA. Methods A total of 31 patients were recruited to this single-group radiostereometric analysis (RSA) study and received a medial pivot GMK Sphere TKA. The distributions of male patients versus female patients and right versus left knees were 21:10 and 17:14, respectively. Mean BMI was 29 kg/m2 (95% confidence interval (CI) 27 to 30) and mean age at surgery was 63 years (95% CI 61 to 66). Maximum total point motions (MTPMs), medial, proximal, and anterior translations and transversal, internal, and varus rotations were calculated at three, 12, and 24 months. Patient-reported outcome measure data were also retrieved. Results MTPMs at three, 12, and 24 months were 1.0 mm (95% CI 0.8 to 1.2), 1.3 mm (95% CI 0.9 to 1.7), and 1.4 mm (0.8 to 2.0), respectively. The Forgotten Joint Score was 79 (95% CI 39 to 95) and Knee Injury and Osteoarthritis Outcome Score obtained at two years was 94 (95% CI 81 to 100), 86 (95% CI 75 to 93), 94 (95% CI 88 to 100), 69 (95% CI 48 to 88), and 81 (95% CI59 to 100) for Pain, Symptoms, Activities of Daily Living, Sport & Recreation, and Quality of Life, respectively. Conclusion In conclusion, we found that the mean increase in MTPM was lower than 0.2 mm between 12 and 24 months and thus apparently stable. Yet the GMK Sphere had higher migration at one and two years than anticipated. Based on current RSA data, we therefore cannot conclude on the long-term performance of the implant, pending further assessment

Identification of femoral head center of bipolar hemiarthroplasy in radiostereometric analysis with elementary geometrical shape models.

Elementary geometrical shape (EGS) models are useful in radiostereometric analysis (RSA) on hip stems because tantalum markers attached to the stems can be omitted. In order to create an EGS model of a femoral stem, the center of the femoral head has to be identified. The contour of the femoral head is recommended to be used. However, the contour of the femoral head cannot be detected exclusively by computer if it is combined with a bipolar head or a metal cup. We therefore hypothesized that the contour of the outer head of bipolar hemiarthroplasty can be included in the EGS model as well as the femoral head contour. We calculated the time required for the detection of the contour, the precision of analysis and the stem micromotion at 2 years using the two different methods in the same picture set and compared the results. The detection of the bipolar head contour was 10 times faster than that of the femoral head contour. The precision for subsidence was 0.16mm in EGS RSA with the femoral head contour, and 0.15mm with the bipolar head contour (p=0.68). The precisions were comparable and clinically acceptable. There was no significant difference between the results of the 2-year micromotion with the two different methods. We conclude that this new method is applicable to measure stem micromotion of hemi-arthoplasty with EGS RSA and the method facilitates the Radiostereometric analysis

A 2-year RSA study of the Vanguard CR total knee system: A randomized controlled trial comparing patient-specific positioning guides with conventional technique

Backgound and purpose - There is some concern regarding the revision rate of the Vanguard CR TKA in 1 registry, and the literature is ambiguous about the effi cacy of patient-specifi c positioning guides (PSPGs). The objective of this study was to investigate the stability of the cemented Vanguard CR Total Knee using 2 different surgical techniques. Our hypothesis was that there is no difference in migration when implanting the Vanguard CR with either PSPGs or conventional technique. We hereby present a randomized controlled trial of 2-year follow-up with radiostereometric analysis (RSA). Patients and methods — 40 TKAs were performed between 2011 and 2013 with either PSPGs or the conventional technique and 22 of these were investigated with RSA. Results — The PSPG (8 knees) and the conventional (14 knees) groups had a mean maximum total point motion (MTPM) (95% CI) of 0.83 (0.48–1.18) vs. 0.70 (0.43–0.97) mm, 1.03 (0.60–1.43) vs. 0.86 (0.53–1.19), and 1.46 (1.07– 1.85) vs. 0.80 (0.52–1.43) at 3, 12, and 24 months respectively (p = 0.1). 5 implants had either an MTPM > 1.6 mm at 12 months and/or a migration of more than 0.2 mm between 1- and 2-year follow-ups. 2 of these also had a peripheral subsidence of more than 0.6 mm at 2 years. Interpretation — 5 implants (3 in the PSPG group) were found to be at risk of later aseptic loosening. The PSPG group continuously migrated between 12 and 24 months. The conventional group had an initial high migration between postoperative and 3 months, but seemed more stable after 1 year. Although the difference was not statistically signifi cant, we think the migration in the PSPG group is of some concernpublishedVersion© 2018 The Author(s). Published by Taylor & Francis on behalf of the Nordic Orthopedic Federation. This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (https://creativecommons.org/licenses/by/4.0

A 2-year RSA study of the Vanguard CR total knee system: A randomized controlled trial comparing patient-specific positioning guides with conventional technique

<p><b>Background and purpose</b> — There is some concern regarding the revision rate of the Vanguard CR TKA in 1 registry, and the literature is ambiguous about the efficacy of patient-specific positioning guides (PSPGs). The objective of this study was to investigate the stability of the cemented Vanguard CR Total Knee using 2 different surgical techniques. Our hypothesis was that there is no difference in migration when implanting the Vanguard CR with either PSPGs or conventional technique. We hereby present a randomized controlled trial of 2-year follow-up with radiostereometric analysis (RSA).</p> <p><b>Patients and methods</b> — 40 TKAs were performed between 2011 and 2013 with either PSPGs or the conventional technique and 22 of these were investigated with RSA.</p> <p><b>Results</b> — The PSPG (8 knees) and the conventional (14 knees) groups had a mean maximum total point motion (MTPM) (95% CI) of 0.83 (0.48–1.18) vs. 0.70 (0.43–0.97) mm, 1.03 (0.60–1.43) vs. 0.86 (0.53–1.19), and 1.46 (1.07–1.85) vs. 0.80 (0.52–1.43) at 3, 12, and 24 months respectively (p = 0.1). 5 implants had either an MTPM >1.6 mm at 12 months and/or a migration of more than 0.2 mm between 1- and 2-year follow-ups. 2 of these also had a peripheral subsidence of more than 0.6 mm at 2 years.</p> <p><b>Interpretation</b> — 5 implants (3 in the PSPG group) were found to be at risk of later aseptic loosening. The PSPG group continuously migrated between 12 and 24 months. The conventional group had an initial high migration between postoperative and 3 months, but seemed more stable after 1 year. Although the difference was not statistically significant, we think the migration in the PSPG group is of some concern.</p

Implant survival and radiographic outcome of total hip replacement in patients less than 20 years old

Background and purpose — Total hip replacement (THR) is not recommended for children and very young teenagers because early and repetitive revisions are likely. We investigated the clinical and radiographic outcomes of THR performed in children and teenage patients. Patients and methods — We included 111 patients (132 hips) who underwent THR before 20 years of age. They were identified in the Norwegian Arthroplasty Register, together with information on the primary diagnosis, types of implants, and any revisions that required implant change. Radiographs and Harris hip score (HHS) were also evaluated. Results — The mean age at primary THR was 17 (11–19) years and the mean follow-up time was 14 (3–26) years. The 10-year survival rate after primary THR (with the endpoint being any revision) was 70%. 39 patients had at least 1 revision and 16 patients had 2 or more revisions. In the latest radiographs, osteolysis and atrophy were observed in 19% and 27% of the acetabulae and 21% and 62% of the femurs, respectively. The mean HHS at the final follow-up was 83 (15–100). Interpretation — The clinical score after THR in these young patients was acceptable, but many revisions had been performed. However, young patients with developmental dysplasia of the hip had lower implant survival. Moreover, the bone stock in these patients was poor, which could complicate future revisions