Shinya Oka

Autophagy modulates osteoarthritis-related gene expression in human chondrocytes

OBJECTIVE Autophagy, an evolutionarily conserved process for the bulk degradation of cytoplasmic components, serves as a cell survival mechanism. The purpose of this study was to elucidate the role of autophagy in human chondrocytes and pathophysiology of osteoarthritis (OA). METHODS Autophagy in articular cartilage and primary chondrocytes was assessed using antibodies for the autophagy markers light chain 3 and beclin 1. The states of autophagy under catabolic and nutritional stresses were examined. We also examined the effects of inhibition or induction of autophagy under stimulation with interleukin-1β. Autophagy was inhibited by small interfering RNA targeting ATG5, and autophagy was induced by rapamycin. The effects of inhibition or induction of autophagy were examined by real-time polymerase chain reaction for aggrecan, COL2A1, MMP13, and ADAMTS5 messenger RNA. To further examine the mechanism of autophagy regulation in OA human chondrocytes, we investigated whether autophagy modulates apoptosis and reactive oxygen species (ROS). RESULTS Autophagy was increased in OA chondrocytes and cartilage. Catabolic and nutritional stresses increased autophagy. In addition, the inhibition of autophagy caused OA-like gene expression changes, while the induction of autophagy prevented them. Furthermore, the inhibition of autophagy increased the amount of cleaved poly(ADP-ribose) polymerase and cleaved caspase 9, while the induction of autophagy inhibited these increases. ROS activity was also decreased by induction of autophagy. CONCLUSION These observations suggested that increased autophagy is an adaptive response to protect cells from stresses, and that autophagy regulates OA-like gene expression changes through the modulation of apoptosis and ROS. Further studies about autophagy in chondrocytes will provide novel insights into the pathophysiology of OA.

Similarities and Differences of Diagnostic Manual Tests for Anterior Cruciate Ligament Insufficiency: A Global Survey and Kinematics Assessment

Background: The Lachman and pivot-shift tests are 2 standard manual tests to diagnose anterior cruciate ligament (ACL) insufficiency. However, the global variation of these testing procedures is not known. Purpose: To survey currently used testing techniques and to measure the knee movement during manual tests among various expert surgeons from across the globe. Study Design: Controlled laboratory study. Methods: Part 1: descriptive survey. A questionnaire asking about testing procedures of Lachman and pivot-shift tests was conducted among 33 ACL surgeons. Part 2: knee kinematics comparison. Lachman and pivot-shift tests were performed on a unilateral ACL-injured patient by 5 surgeons, while knee kinematics was recorded by an electromagnetic system. Tibial translation was measured during the Lachman test, while tibial translation, rotation, and pivot-shift acceleration were calculated during the pivot-shift test. Results: Part 1: Tibial anterior drawer by a medially placed hand was widely advocated for the Lachman test. Flexion type of the pivot-shift test maneuver was supported by two thirds, while extension type was supported by one third. However, the “feeling” of subluxation or reduction during the pivot shift was the primary evaluation method used by the vast majority of surgeons. Part 2: Increased tibial translation during the Lachman test was observed in the ACL-injured knee with significant variation between examiners (P < .01). Tibial translation and pivot-shift acceleration during the pivot-shift test increased in the ACL-injured side (P < .01), but tibial rotation was too diverse to find any trend (P = .31). Tibial translation and acceleration of the pivot shift in the ACL-injured knee showed no significant difference between examiners (P > .05). Conclusion: The Lachman test can display a wide variation of actual movement despite maneuver similarity, while the pivot-shift test could possibly be measurable by tibial translation and/or acceleration beyond their procedural variation. Clinical Relevance: We should recognize the limitations of these manual tests and the possibilities of their objective measurement.

Acceleration of Tendon-Bone Healing of Anterior Cruciate Ligament Graft Using Autologous Ruptured Tissue

Background: It has been recently reported that human anterior cruciate ligament (ACL) ruptured tissue contains abundant vascular stem cells that contribute to tendon-bone healing in an immunodeficient rat model of ACL reconstruction. Hypothesis: Autologous ruptured ACL tissue has an effect on the maturation of bone-tendon integration in anterior cruciate ligament reconstruction. Study Design: Controlled laboratory study. Methods: Twenty healthy adult beagle dogs underwent bilateral ACL reconstruction using the ipsilateral flexor digitorum superficialis tendon and were divided into 2 groups: right knee (a tissue-treated group) and left knee (a control group). The tissue-treated group received autologous ruptured ACL tissue, which was obtained 2 days after resection and sutured to the tibial side of the graft. Histological, radiographic, and biomechanical assessments were performed. In addition, immunohistochemical staining was performed to assess angiogenesis and osteogenesis. Results: Histological assessment and staining for osteoblasts and endothelial cells at week 2 demonstrated early healing, inducing endochondral ossification-like integration with enhanced angiogenesis and osteogenesis in the tissue-treated group’s grafts. Computed tomography at week 4 showed a significantly smaller tibial bone tunnel in the tissue-treated group (tissue, 19.0 ± 4.4 mm2; control, 42.6 ± 4.7 mm2; P = .009, n = 5). Furthermore, biomechanical testing of force during loading to ultimate failure at week 4 demonstrated a significantly higher strength in the tissue-treated group (tissue, 66.4 ± 10.1 N; control, 30.5 ± 10.3 N; P = .009, n = 5). Conclusion: In the present study, the authors elucidated that transplantation of ACL-ruptured tissue, which was sutured to the tibial side of the graft, contributed to early tendon-bone healing in a canine model of ACL reconstruction. Clinical Relevance: Anterior cruciate ligament ruptured tissue has a therapeutic potential in promoting an appropriate environment for tendon-to-bone healing in bone tunnels of ACL reconstruction.

Kinematic factors affecting postoperative knee flexion after cruciate-retaining total knee arthroplasty.

PurposeThe purpose of this study was to investigate kinematic factors affecting postoperative knee flexion after cruciate-retaining (CR) total knee arthroplasty (TKA) by analysing pre- and postoperative knee kinematics.MethodsWe retrospectively analysed 58 patients with osteoarthritis who received the same implant series. Pre- and postoperative kinematics were measured intraoperatively using a navigation system. As a clinical outcome, we measured the knee flexion angle before and one year after surgery. Correlations among pre- and postoperative kinematics and postoperative flexion were analysed using simple linear regression analyses.ResultsPreoperative knee kinematics, including tibial internal rotation and anterior translation (R = 0.87, P < 0.001; R = 0.53, P < 0.001, respectively), were significantly correlated with postoperative kinematics. Preoperative varus–valgus movements improved significantly postoperatively; however, tibial internal rotation remained unchanged. Furthermore, postoperative knee flexion angle was significantly correlated with postoperative tibial internal rotation (R = 0.45, P < 0.001).ConclusionsPreoperative knee kinematics were unchanged even after CR-TKA. Postoperative tibial internal rotation is one of the most important factors affecting postoperative knee flexion.

Soft tissue balance measurement in minimal incision surgery compared to conventional total knee arthroplasty.

PurposesMinimal incision surgery (MIS) total knee arthroplasty (TKA) is widely promoted as a possible improvement over conventional TKA, and accurate implantations have recently been reported using navigation systems. However, soft tissue balance during MIS-TKA remains challenging. Therefore, in this report, joint gap (component gap) and ligament balance (varus angle) were assessed during MIS-TKA using a tensor, which enables soft tissue balance assessment with a reduced patellofemoral joint and femoral component in place.MethodsResults were compared to those of conventional TKA. Posterior stabilized TKA were performed in 50 knees (25 knees: MIS-TKA using quadriceps-sparing approach; 25 knees: conventional TKA using medial parapatellar approach) with varus osteoarthritis. Component gap and varus angle were measured using the tensor with a reduced patellofemoral joint at 0, 10, 45, 90, and 135°.ResultsWhereas the component gap in MIS-TKA was significantly larger through the entire arc of flexion compared with conventional TKA, the pattern of joint looseness showed no difference between the two procedures. The varus angle in MIS-TKA was significantly larger than that in conventional TKA at 0, 90, and 135° of knee flexion.ConclusionsMIS-TKA may lead to ligament imbalance due to the difficulties induced by a limited working space. Understanding this pattern allows surgeons to be able to adjust the soft tissue balance more accurately and thereby expect a better post-operative outcome even in MIS-TKA.

Three-Dimensional Analysis of Bone Tunnel Changes After Anatomic Double-Bundle Anterior Cruciate Ligament Reconstruction Using Multidetector-Row Computed Tomography

Background: The femoral and tibial bone tunnel enlargement after anatomic double-bundle anterior cruciate ligament reconstruction (ACL-R) has not been fully documented. Purpose: To evaluate the region-specific bone tunnel volume changes and those transpositions using 3-dimensional multidetector-row computed tomography (MDCT) after anatomic double-bundle ACL-R. Study design: Case series; Level of evidence, 4. Methods: Eleven patients who underwent unilateral double-bundle ACL-R with hamstring tendon autografts were included in this study. MDCT scanning of their knees was performed at 3 weeks and 1 year after surgery. The bone tunnel regions were extracted from the MDCT images, and the longitudinal axis of each bone tunnel was divided into 3 equal sections. The centroids of the outside and the articular thirds were then extracted from the bone tunnel position. Changes in the bone tunnel volume and the transposition of the articular third were calculated and compared. Results: At 1 year postoperatively, as compared with the 3-week postoperative value (set at 100%), the femoral bone tunnel volume of the anteromedial bundle (AMB) and posterolateral bundle (PLB) changed to 77.4% ± 15.3% and 102.3% ± 19.2% in the outside third and 122.3% ± 31.8% and 112.5% ± 34.4% in the articular third, respectively. The tibial bone tunnel volume of the AMB and the PLB changed to 108.6% ± 28.7% and 105.4% ± 22.6% in the tibial articular third and 54.9% ± 25.8% and 52.5% ± 26.9% in the outside third, respectively. The femoral outside third of the AMB and the tibial outside third of both the AMB and PLB were significantly reduced in bone tunnel volume. The centroid of the femoral articular third of the AMB moved 13°, 1.1 ± 0.6 mm posterodistally, and that of the PLB moved 35°, 0.8 ± 0.4 mm anterodistally. Furthermore, the centroid of the tibial articular third of the AMB moved 14°, 2.0 ± 1.6 mm posterolaterally, and that of the PLB moved 72°, 1.0 ± 1.3 mm posterolaterally. Conclusion: Compared with 3 weeks postoperatively, the articular side outlets of the femoral and tibial bone tunnels at 1 year postoperatively had enlarged slightly but statistically maintained their volume, and they had moved a little in the direction that the grafts were pulled.

Soft tissue balance using the tibia first gap technique with navigation system in cruciate-retaining total knee arthroplasty

PurposeThe procedures of bone cut and soft tissue balancing in total knee arthroplasty (TKA) are usually performed using the measured resection technique or the gap technique; however, the superiority of these techniques is controversial. An increase of extension gap after resection of the femoral posterior condyle and a difference between gaps before and after femoral component placement have been reported. We therefore postulated that the use of the tibia first gap technique might have an advantage in avoiding the mismatch before and after resection of the femoral posterior condyle and femoral component placement.MethodsWe performed cruciate-retaining TKAs for 60 varus type osteoarthritic patients with tibia first gap technique using a CT-free navigation system. A TKA tensor designed to facilitate soft tissue balance measurements throughout the range of motion with a reduced and repaired patello-femoral joint was used to assess soft tissue balance (joint gap and varus ligament balance) at extension and flexion between the basic value after tibial cut and the final value following femoral cut and with the femoral component in place.ResultsWhereas varus ligament balance at flexion showed significant decrease in the final value at flexion due to the amount of femoral rotation, the basic value of the joint gap before femoral osteotomy reflected the final value following femoral cut and with the femoral component in place.ConclusionThe tibia first gap technique may have the advantage that surgeons can predict final soft tissue balance before femoral osteotomies.

The influence of patellar position on soft tissue balance in minimal incision total knee arthroplasty

PurposeThis study aims to clarify the influence of surgical exposure on intra-operative soft tissue balance measurements using a new tensor in minimal incision total knee arthroplasty (TKA).MethodsSixty patients with osteoarthritis of the knee received minimal incision TKAs. Twenty patients received a posterior-stabilized TKA using a quadriceps sparing approach, and the other forty patients, using a limited medial parapatellar (mini) approach. After femoral trial placement, soft tissue balance was measured using an offset type tensor at full extension and 90° of knee flexion, with the patella both laterally retracted and reduced. The joint component gap and varus imbalance were used to assess the difference in patellar position and surgical exposure.ResultsAt extension, the joint component gap and varus imbalance showed no statistical difference regardless of patellar position in either TKA. However, the joint component gaps decreased at 90° of flexion when the patella was laterally retracted in both TKAs. Additionally, a significantly smaller joint gap was observed in the quadriceps sparing TKA than the mini-TKA with a retracted patella at 90° of flexion. Varus ligament imbalances decreased with the patella laterally retracted at 90° of flexion in the quadriceps sparing TKA, not in the mini-TKA.ConclusionSurgeons should be aware of the influence in surgical exposure of the joint gap and ligament balance during patella shift in minimal incision TKA.Level of evidenceIII.

Differences in Knee Kinematics Between Awake and Anesthetized Patients During the Lachman and Pivot-Shift Tests for Anterior Cruciate Ligament Deficiency

Background: The Lachman and pivot-shift tests have been widely used for detecting anterior cruciate ligament (ACL) deficiency. However, it still remains unclear whether these manual tests can be quantified accurately while patients are awake. Purpose: To assess the differences in knee kinematics of awake and anesthetized patients. Study Design: Case series; Level of evidence, 4. Methods: A total of 50 patients with unilateral ACL rupture were examined. Anteroposterior tibial translation was assessed using a KT-1000 arthrometer at maximal manual power. Anterior tibial translations during the manual Lachman test and the acceleration of tibial posterior translation (APT) during the pivot-shift test were also measured using an electromagnetic measurement system (EMS). All 3 measurements were performed on the day previous to surgery while the patients were awake and on the operative day before the surgery while the patients were under general anesthesia. Results: The mean side-to-side difference in anteroposterior tibial translation was 5.6 ± 2.6 mm in the awake state and 5.9 ± 3.5 mm under anesthesia, indicating a nonsignificant difference. According to the EMS, the mean side-to-side difference in anteroposterior tibial translation during the Lachman test was 4.6 ± 3.6 mm in the awake state and 6.9 ± 4.3 mm under anesthesia, indicating a significant difference (P < .01). The mean APT during the pivot-shift test was −0.8 ± 0.3 m/s2 in intact knees and −1.1 ± 0.4 m/s2 in ACL-deficient knees when the patients were awake and was −0.7 ± 0.2 m/s2 and −1.7 ± 1.0 m/s2, respectively, when the patients were under anesthesia. In ACL-deficient knees, the APT pivot-shift test result was significantly higher when the patients were under anesthesia than when they were awake (P < .01). Conclusion: In ACL-deficient knees, the knee kinematics during the Lachman and pivot-shift tests is significantly affected by patient consciousness, and caution is needed in quantifying anterior knee laxity during these tests when the patients are awake.

Simulation of the optimal femoral insertion site in medial patellofemoral ligament reconstruction.

PurposeTo develop and validate a new simulation system to predict the optimal femoral insertion site of the medial patellofemoral ligament (MPFL) using preprogrammed conditions of graft length change.MethodsA computed tomography scan was performed for constructing bone surface models of the patella and the femur. Lateral radiographs of the knee and axial radiographs of the patellofemoral joint at knee flexion were used for constructing a three-dimensional patellofemoral joint model by 3D–2D image matching at each knee flexion angle. To determine the optimal femoral insertion site, the following three conditions were devised: (1) MPFL behaves isometric from 0° to 60°, (2) MPFL is most taut at full extension, and (3) MPFL is slack at more than 60° of knee flexion. Every condition was applied to the femoral bone surface model, and the area that fulfilled all three conditions was defined as the optimal femoral insertion site of MPFL. Twenty knees of ten healthy volunteers were assessed to verify the simulation. Comparison between simulated optimal femoral insertion and anatomical insertion was done.ResultsThe mean simulated optimal femoral insertion was close to the anatomical insertion site. There were no significant differences in the proximal–distal position and anterior–posterior position between the simulated insertion and the anatomical insertion sites.ConclusionThe system can be useful for predicting the optimal femoral insertion site as a part of a preoperative plan for MPFL reconstruction, and it may help surgeons to determine the optimal femoral insertion site during MPFL reconstruction.