Alteration of knee joint moment after anterior cruciate ligament reconstruction conditions in subjects with and without meniscal pathology.

BACKGROUND: The effects of anterior cruciate ligament (ACL) reconstruction on postoperative gait biomechanics remain controversial, and the influence of meniscus pathology on pre- and post-ACL reconstruction biomechanical changes has not yet been studied. Here, we aimed to clarify the difference in knee joint moment between pre- and post-ACL reconstruction conditions in subjects with and without meniscal pathology. METHODS: Twenty-four subjects with unilateral ACL reconstruction injuries participated in this study. A total of 13 of the subjects had concomitant meniscus injuries. Gait analysis was performed preoperatively and at 11 months postoperatively. Three-dimensional knee joint angles and moments were calculated based on motion-capture data. The total joint moment and contribution of individual moments during the stance phase were assessed. For statistical analysis, we compared pre- and postoperative alterations, and differences were assessed in subjects with and without meniscal pathology. RESULTS: Tibial rotation excursion was lower in subjects with meniscal pathology than in those with intact menisci postoperatively. An significant increase in the contribution of the knee flexion moment and a significant decrease in the contribution of the knee adduction moment postoperatively were observed in subjects with intact menisci. CONCLUSIONS: Patients with ACL injury showed different postoperative alterations in joint moments depending on the concomitant meniscal injury.

Turning and sitting movements during timed up and go tests predict deterioration of physical function in middle-aged adults.

BACKGROUND: Deterioration of physical function in middle-aged adults is a significant challenge that can lead to increased risk of future falls. However, a screening method for the functional decline in middle-aged adults has not been established. RESEARCH QUESTION: To evaluate the relationship between biomechanical parameters assessed by the timed up and go test (TUG) and locomotive syndrome (LS) in middle-aged adults. METHODS: The inclusion criterion was: under 65 years of age. A total of 97 volunteers (mean age 51.1 years) participated in this study. An LS test was performed, including a 2-step test, a stand-up test, and a 25-question Geriatric Locomotive Function Scale. The TUG was measured using inertial measurement units (IMUs) at comfortable and fast speeds. We then determined the minimum values for anterior-posterior acceleration and angular velocity around the medial-lateral axis, as well as the maximum values of angular velocity around the vertical axis for the upper trunk and sacrum in a TUG phase. RESULTS: Angular velocity around the vertical axis for upper trunk and sacrum were significantly smaller in LS than non-LS in the turn phase of both speed conditions. For the fast speed condition, the minimum anterior-posterior acceleration for sacrum was greater in LS than in the non-LS condition for the stand-to-sit phase. Angular velocity around the vertical axis for turning and anterior-posterior acceleration from sitting were associated with detection of LS. SIGNIFICANCE: Turning and sitting movements during TUG should be observed using IMU to screen for physical function decline in middle aged adults.

Bilateral Medial and Lateral Discoid Menisci: A Case Report.

Introduction: A discoid meniscus is a typical anatomical variation of the knee. There are several cases of either lateral or medial discoid menisci; however, their combination is rare. We describe a rare instance of bilateral discoid medial and lateral menisci. Case Report: A 14-year-old boy who developed left knee pain after twisting his knee at school was referred to our hospital. He had limited extension of -10°, lateral clicking, and pain on the McMurray test in the left knee and complained of slight clicks in the right knee. Magnetic resonance imaging results for both knees revealed discoid medial and lateral menisci. Surgery was performed on the symptomatic left knee. Arthroscopically, a Wrisberg-type discoid lateral meniscus and an incomplete-type medial discoid meniscus were confirmed. The symptomatic lateral meniscus was saucerized and sutured and only the asymptomatic medial meniscus was observed. The patient was doing well 24 months after surgery. Conclusion: We report a rare case of bilateral medial and lateral discoid menisci.

Lateral Patellar Facetectomy Reduces the Incidence of Anterior Knee Pain in Patellar Resurfaced Total Knee Arthroplasty.

Lateral patellar facet impingement (LPFI) can cause anterior knee pain (AKP) after patellar resurfaced total knee arthroplasty (TKA). Recently, lateral patellar facetectomy (LPF), which has been used for LPFI, has been performed during primary TKA, providing good clinical outcomes. However, the effect of LPF on AKP in primary patellar resurfaced TKA has not been sufficiently studied. The purpose of this study was to examine the effect of LPF on the development of AKP in patellar resurfaced TKAs with minimum follow-up of 3 years. This retrospective cohort study included 84 knees of 66 consecutive patients who underwent patellar resurfaced TKA between April 2007 and November 2014 in our hospital. The subjects were divided into two groups: TKA with LPF (LPF group; 47 knees) and TKA without LPF (no-LPF group; 37 knees). Postoperative AKP, the primary outcome, the Japanese Orthopaedic Association (JOA) score, and range of motion were investigated at the final visit and compared between the two groups. Six knees (16.2%) had AKP in the no-LPF group, whereas none of the knees had AKP in the LPF group at the final visit. The incidence of AKP was significantly lower in the LPF group (p = 0.004). The postoperative JOA score and flexion angle were significantly higher in the LPF group than in the no-LPF group. LPF correlated with less incidence of postoperative AKP and improved the JOA score and knee flexion angle. In patellar resurfaced TKA, LPF may be considered an additional maneuver to avoid postoperative AKP.

The Stat3 inhibitor F0648-0027 is a potential therapeutic against rheumatoid arthritis.

Rheumatoid arthritis (RA) is a disease characterized by chronic joint inflammation, pain and joint destruction, leading to alteration in activities of daily living, yet pathological mechanisms underlying the condition are not fully clarified. To date, various therapeutic agents have been developed as RA therapy including DMARDs and/or biological agents that target inflammatory cytokines or inhibit JAK. Here we asked whether inhibiting signal transducer and activator of transcription 3 (Stat3) activity would antagonize RA. Stat3 forms dimers when activated and undergoes nuclear translocalization; thus we screened approximately 4.9 million small compounds as potential blockers of protein-protein interactions required for Stat3 dimerization using in silico screening. We identified 15 as strong candidates as potential blockers of protein-protein interactions required for Stat3 dimerization using in silico screening from those compounds. Four of the 15 significantly inhibited expression of IL-6 and RANKL, both of which are direct targets of Stat3, induced by IL-6. Among four, one compound, F0648-0027, significantly inhibited arthritis development without apparent adverse effects in vivo in collagen-induced arthritis model mice. F0648-0027 also significantly blocked Stat3 phosphorylation and nuclear localization following IL-6 stimulation of fibroblasts. These data suggest that Stat3 is a target for collagen-induced arthritis in mice, and that F0648-0027 could serve as a therapeutic reagent against comparable conditions in humans.

Goals, challenges and strategies for wound and bleeding management in total knee arthroplasty: A modified Delphi method.

BACKGROUND: Surgical techniques related to soft tissue management play critical roles in optimizing surgical outcomes and patient satisfaction in total knee arthroplasty (TKA). Despite the importance of wound closure and bleeding management approaches, no published guidelines/consensus are available. METHODS: Twelve orthopedic surgeons participated in a modified Delphi panel consisting of 2 parts (each part comprising two rounds) from September-October 2018. Questionnaires were developed based on published evidence and guidelines on surgical techniques/materials. Questionnaires were administered via email (Round 1) or at a face-to-face meeting (subsequent rounds). Panelists ranked their agreement with each statement on a five-point Likert scale. Consensus was achieved if ≥70% of panelists selected 4/5, or 1/2. Statements not reaching consensus in Round 1 were discussed and repeated or modified in Round 2. Statements not reaching consensus in Round 2 were excluded from the final consensus framework. RESULTS: Consensus was reached on 13 goals of wound management. Panelists agreed on 38 challenges and 71 strategies addressing surgical techniques or wound closure materials for each tissue layer, and management strategies for blood loss reduction or deep vein thrombosis prophylaxis in TKA. Statements on closure of capsular and skin layers, wound irrigation, dressings and drains required repeat voting or modification to reach consensus. CONCLUSION: Consensus from Asia-Pacific TKA experts highlights the importance of wound management in optimizing TKA outcomes. The consensus framework provides a basis for future research, guidance to reduce variability in patient outcomes, and can help inform recommendations for wound management in TKA.

Pain detect questionnaire and pain catastrophizing scale affect gait pattern in patients with knee osteoarthritis.

PURPOSE: Although pain phenotype affects clinical score in patients with knee osteoarthritis (OA), little information has been available on the relationship between pain phenotype and gait analysis. The purpose was to investigate the relationship between pain phenotype and gait parameters.  METHODS: A total of 34 patients (24 females and 10 males) with end-stage medial compartmental knee OA participated. All the patients were evaluated based on pain detect questionnaire (PD-Q) and pain catastrophizing scale (PCS). They were divided into two categories: Group Low (PD-Q score ≤ 12) and Group High (PD-Q score > 12), PCS + (PCS ≥ 23) and PCS- (PCS < 23). Gait analysis was performed using three-dimensional motion analysis system. Statistical analysis was done to compare gait parameters between groups for each allocation of PD-Q or PCS, separately.  RESULTS: Peak vertical ground reaction forces in Group Low and High were 0.99 ± 0.054 and 0.82 ± 0.17, respectively (P = 0.015). Peak knee adduction moments in Group Low and High were 0.70 ± 0.19 and 0.39 ± 0.14, respectively (P = 0.0022). For PCS allocation, knee extension limitation during mid-stance during gait were significantly larger in PCS- (P = 0.038). CONCLUSIONS: Patients with high PD-Q score had atypical gait pattern with smaller peak vertical ground reaction force and knee adduction moment, compared to patients with low PD-Q score. Moreover, patient with low PCS had different gait pattern in extension limitation, compared to those with high PCS. PD-Q and PCS would affect gait pattern in patients with knee OA. LEVEL OF EVIDENCE: III.

Knee varus alters three-dimensional ankle alignment in standing- a study with upright computed tomography.

BACKGROUND: For knee osteoarthritis (OA) treatment, it is important to correct the lower limb alignment including the foot. However, in the upright position, lower limb alignment is generally assessed from the body surface or radiographs, and it is a challenge to capture the exact characteristics of three-dimensional lower limb alignment. The purpose of the study was to measure lower limb alignment in patients with knee OA using upright computed tomography (CT) and radiography, and to identify features of knee joint deformity. METHODS: A total of 45 limbs in 25 patients with knee OA were enrolled. The subjects underwent both upright CT and radiography for the whole lower limb in the standing position. The joint angles were calculated on both images. The degree of knee OA was classified according to Kellgren-Lawrence (KL) grade by referring to radiography, which is mainly based on the degree of articular cartilage loss and severity of osteophytes, and the characteristics or correlation between knee and ankle joint in each group was investigated. RESULTS: In KL-I, there was an association between varus of the knee joint and internal rotation of the talocrural joint (r = 0.76, P < 0.05). In KL-II, there was an association between varus of the knee joint and eversion of the subtalar joint (r = 0.63, P < 0.05) and talocrural joint (r = - 0.65, P < 0.05). In KL-III, there was an association between varus of the knee joint and internal rotation of the subtalar joint (r = - 0.62, P < 0.05), and in KL-IV, there was an association between varus of the knee joint and internal rotation of the subtalar joint (r = - 0.58, P < 0.05). CONCLUSIONS: The lower limb alignment of patients with knee OA in the standing position was found that as knee OA worsened, it became apparent that compensatory knee joint alignment depended on the ankle joint rather than the subtalar joint. The results may help in the rehabilitation of patients with knee OA, since the ankle joint alignment has a significant impact on the knee joint during coarse movements involving load.

Biomechanical features of drop vertical jump are different among various sporting activities.

BACKGROUND: Risk for non-contact anterior cruciate ligament (ACL) injury can be assessed based on drop vertical jump (DVJ). However, biomechanics of DVJ may differ with various sporting activities. The purpose of the present study was to clarify whether biomechanical features of DVJ are different among various sporting activities in female athletes. METHODS: A total of 42 female athletes, including 25 basketball, 8 soccer and 9 volleyball players, participated in the current investigation. DVJ was done for each female athlete using a three-dimensional motion analysis system which consisted of six cameras, two force plates and 46 retro-reflective markers. Kinematic and kinetic data were recorded for both limbs in each athlete. Simultaneously, frontal and sagittal plane views of the DVJ were recorded using two different high-resolution video cameras to evaluate Landing Error Scoring System (LESS) score. Three-dimensional biomechanical parameters at the knee joint and LESS were compared among three different sporting activities using ANOVA or Kruskal-Wallis test after confirming normality assumption. Thereafter post hoc Tukey or Steel-Dwass was utilized for multiple comparison. RESULTS: Soccer players had better LESS score, and peak knee flexion angle was significantly larger in soccer players compared to the other sports. In addition, knee abduction angle at initial contact (IC), peak knee abduction angle, knee internal rotation angle, and knee abduction moment within 40 ms from IC were significantly smaller in soccer players, compared to basketball players. In terms of volleyball players, knee abduction angle at IC and knee internal rotation angle at IC were significantly larger than soccer players, whereas no significant biomechanical differences were found between basketball and volleyball players. CONCLUSIONS: From the present study, female basketball and volleyball players have worse LESS score, smaller peak knee flexion angle, greater knee abduction angle at IC and greater knee internal rotation angle at IC, compared to female soccer players. Thus, female basketball and volleyball players may have an increased risk of non-contact ACL injury during the jump-landing task, compared to soccer players. Biomechanics of DVJ depends on characteristics of the athlete's primary sport.

Effects of Dual Task Interference on Biomechanics of The Entire Lower Extremity During the Drop Vertical Jump.

The dual task is an important factor affecting knee biomechanics during jump-landing tasks. Athletes often have trouble in performing two tasks concurrently and a dual task can deteriorate landing performance. However, it is still unknown whether a dual task will affect the entire lower extremity. The purpose of this study was to clarify the effects of cognitive task interference on biomechanics of hip and ankle joints as well as the knee joint during the drop vertical jump (DVJ). A total of 20 female collegiate athletes participated in the study. Athletes performed a DVJ with or without a cognitive task. The DVJ was captured using a motion analysis system. Mental arithmetic of 2-digit addition was used as a cognitive task. Maximum vertical ground reaction force (vGRF), joint angles at initial contact (IC), joint moments within 40 milliseconds (ms) after IC, and joint angles and moments at peak vGRF were assessed. The data were statistically compared between with and without a cognitive task condition using a two-tailed paired t-test or the Wilcoxon singed rank test. The peak external knee abduction moment on both limbs within 40 ms after IC during the DVJ was significantly larger in the dual task than in the single task with less knee and hip flexion at initial contact. In addition, all moments of hip and ankle joints within 40 ms after IC were significantly larger in the dual task than in the single task accompanied with greater vGRF, except for the hip internal rotation moment. Cognitive tasks during a DVJ will result in biomechanical changes of the entire lower extremity in female athletes.

Increase in tibial internal rotation due to weight-bearing is a key feature to diagnose early-stage knee osteoarthritis: a study with upright computed tomography.

BACKGROUND: The classification of knee osteoarthritis is an essential clinical issue, particularly in terms of diagnosing early knee osteoarthritis. However, the evaluation of three-dimensional limb alignment on two-dimensional radiographs is limited. This study evaluated the three-dimensional changes induced by weight-bearing in the alignments of lower limbs at various stages of knee osteoarthritis. METHODS: Forty five knees of 25 patients (69.9 ± 8.9 years) with knee OA were examined in the study. CT images of the entire leg were obtained in the supine and standing positions using conventional CT and 320-row detector upright CT, respectively. Next, the differences in the three-dimensional alignment of the entire leg in the supine and standing positions were obtained using 3D-3D surface registration technique, and those were compared for each Kellgren-Lawrence grade. RESULTS: Greater flexion, adduction, and tibial internal rotation were observed in the standing position, as opposed to the supine position. Kellgren-Lawrence grades 1 and 4 showed significant differences in flexion, adduction, and tibial internal rotation between two postures. Grades 2 and 4 showed significant differences in adduction, while grades 1 and 2, and 1 and 3 showed significant differences in tibial internal rotation between standing and supine positions. CONCLUSIONS: Weight-bearing makes greater the three-dimensional deformities in knees with osteoarthritis. Particularly, greater tibial internal rotation was observed in patients with grades 2 and 3 compared to those with grade 1. The greater tibial internal rotation due to weight-bearing is a key pathologic feature to detect early osteoarthritic change in knees undergoing osteoarthritis.

Application of an indentation sensor for the arthroscopic measurement of articular cartilage stiffness.

Direct measurement of cartilage stiffness provides useful clinical information and enables us to develop treatment strategies for patients. We applied an indentation sensor to evaluate cartilage stiffness under arthroscopic control. The purpose of this study was to validate the arthroscopic indentation sensor using cadaver knees and to measure cartilage stiffness in clinical cases. The stiffness of a material with known properties was measured at thicknesses from 2 mm to 10 mm with a 2-mm interval. This was repeated three times at each thickness to evaluate repeatability. The articular cartilage stiffness of the medial and lateral femoral condyles of five human cadaveric knees was measured. The sensor was inclined from 0° to 20° with 1° intervals. The stiffness value at each degree of inclination was compared to evaluate the acceptable measuring angle. Additionally, articular cartilage stiffness was measured in 23 adolescent and 11 adult patients under arthroscopy. Young's moduli of the material were 1.15-1.24 (mean 1.20) MPa. Inter-class correlation coefficients in repeated measurements using the material were 0.83-0.99. There were no differences in the cartilage stiffness between the medial and lateral femoral condyles of the cadaver knees. All condyles showed a nonlinear relationship between force and displacement. The force decreased in all condyles when the tip of the sensor system was tilted. The range of error was < 97.1% within 5° inclination. There was a moderate negative correlation between age and cartilage stiffness in adolescent patients, and a moderate positive correlation in adult patients. Since the sensor system is manually held during measurement, the validity and repeatability to assess material properties of the cartilage may be inaccurate. This study has proven that the instrument can measure the stiffness of joint cartilage reliably and is a useful clinical tool under arthroscopic control.

Four-dimensional computed tomographic analysis of screw home movement in patients with anterior cruciate ligament deficient knee - a 3D-3D registration technique.

OBJECTIVE: The tibia externally rotates to the femur during the last 20° of the knee extension motion. This kinematic phenomenon is well known as screw home movement (SHM). The purpose was to clarify the SHM in anterior cruciate ligament deficient (ACLD) knee using four-dimensional computed tomography (4DCT). MATERIALS AND METHODS: Six patients with a unilateral isolated ACLD knee participated. In the static position, CT scan of the both limbs of the femur and tibia were performed. Then, 4DCT was performed around knee. In the CT gantry, subjects were positioned in supine position with 45° of knee flexion on a triangle pillow and were asked to extend the knee to full extension within 10 s on each limb. The CT data were accumulated in digital imaging and communication in medicine (DICOM) data format. From the static CT and 4DCT DICOM data, three-dimensional surfaces of the knee joint were reconstructed. The whole tibia surface was matched into the partial tibia surface of that frame using 3D-3D registration technique. After the assessment of coordination system of the whole leg, knee flexion, abduction, and external rotation angle were calculated. RESULTS: Knee external rotation angle was significantly smaller on the ACLD side than on the contralateral unaffected side in 0-15° of knee flexion (P < 0.05 in 0, 5, 10, and 15 degrees), while the angle was similar during 15-60° of knee flexion. CONCLUSION: The absence of SHM in ACLD knee was detected using 3D-3D registration technique based on 4DCT.

Effects of foot progression angle on kinematics and kinetics of a cutting movement.

PURPOSE: Foot progression angle is a key factor for biomechanical knee load, which is associated with noncontact anterior cruciate ligament (ACL) injury during sports-specific tasks. The purpose of the present study was to assess the biomechanics of trunk, pelvis, and lower extremities during a cutting maneuver under different foot progression angles. METHODS: Nineteen male collegiate athletes (ages 18-24) participated in the present study. Cutting motion was analyzed using eight infrared cameras (250 Hz), two force plates (1250 Hz), and 44 reflective markers. Subjects performed 45-degree side cutting maneuvers under three foot progression angles, including 20 degrees (toe-out: TO), 0 degrees (neutral: TN), and - 20 degrees (toe-in: TI). Peak values of each biomechanical parameters in trunk, pelvis, hip, and knee within a first 40% stance phase and each parameter at the timing of the peak vertical ground reaction force were assessed. A statistical analysis was performed to compare data among the three-foot progression angles using the Friedman test. RESULTS: Peak angles of knee abduction, tibial internal rotation, hip internal rotation, and hip adduction were significantly greater for TI position than for TO position (p < 0.01). Peak moments of knee abduction and tibial internal rotation under TI position were also significantly larger than TO position (p < 0.01). Moreover, greater peak pelvis-trunk rotation was found for TI position than for TN and TO positions (p < 0.01). CONCLUSION: From the present study, TI position could lead to an increased risk of ACL injury during a pre-planned cut maneuver, compared to TO position.

Kinematically Aligned Total Knee Arthroplasty Using Medial Pivot Knee Prosthesis Enhances Medial Pivot Motion: A Comparative Kinematic Study With Mechanically Aligned Total Knee Arthroplasty.

BACKGROUND: Clinical outcomes of kinematically aligned total knee arthroplasty (KA-TKA) have been reported as comparable or superior to those of mechanically aligned TKA (MA-TKA). However, cruciate-retaining prostheses have mostly been used for KA-TKA. This study used medial pivot knee prostheses for KA-TKA, and knee kinematics after KA-TKA were assessed and compared with those after MA-TKA. METHODS: Thirteen knees in 9 patients undergoing primary TKA (8 KAs, 5 MAs) were subjected to two-dimensional (2D) to three-dimensional (3D) registration analysis at 1 year postoperatively. Each patient performed weight-bearing activities, and movements were recorded as intermittent digital radiographic images. Three-dimensional implant positions during activities were analyzed for anterior-posterior translation in the sagittal plane, condylar liftoff and mediolateral translation in the coronal plane, and femoral rotation in the axial plane. RESULTS: Posterior translation of the lateral femoral condyle from 0° to 100° was larger in KA-TKA than in MA-TKA (P = .006). The degrees of condylar liftoff and mediolateral translation were comparable between TKAs. Total external rotation of the femoral component relative to tibial component was significantly greater for KA-TKA (7.7 ± 5.2°) than for MA-TKA (1.3 ± 3.3°; P = .03). The kinematic path of the femoral component revealed greater medial pivoting motion in KA-TKA than in MA-TKA. CONCLUSIONS: KA-TKA using a medial pivot knee prosthesis successfully reproduced the medial pivot pattern and achieved larger femoral external rotation relative to the tibia than MA-TKA. KA-TKA was able to maximize the primary concept of the medial pivot knee prosthesis.

Fatigue and recovery have different effects on knee biomechanics of drop vertical jump between female collegiate and recreational athletes.

BACKGROUND: Although fatigue is known as one of the risk factors for noncontact anterior cruciate ligament injury, the effects of fatigue and recovery can be different based on the level of competition. However, it is unknown whether female recreational athletes are susceptible to fatigue or not, compared to female collegiate athletes with greater physical activity. The purpose of the present study was to examine and clarify the effects of fatigue and recovery on knee biomechanics of the drop vertical jump (DVJ) in female recreational athletes compared to female collegiate athletes. METHODS: Fifteen female collegiate athletes and ten female recreational athletes were enrolled in the current study. All subjects were basketball players and Tegner activity scales were level 9 and 7, respectively. They performed DVJ before and after the fatigue protocol. Three-dimensional knee kinematics and kinetics were collected during landing phase of DVJ. The data after the fatigue protocol (first, second, and third DVJs) were compared with those before the protocol using one-way repeated measures of analysis of variance in each group. RESULTS: Fatigue caused significant increase of knee abduction angle at initial contact (IC) and peak abduction moments within 40 ms from IC in female recreational athletes, whereas no increases of these parameters were observed in female collegiate athletes. Moreover, recovery from fatigue seemed to be more slowly in female recreational athletes than in female collegiate athletes as smaller knee flexion moment was observed even in post-fatigue third DVJ only for female recreational athletes. CONCLUSIONS: Effects of fatigue on DVJ were significantly greater and continued for a longer duration in female recreational athletes compared to female collegiate athletes.

Adipose-Derived Stem Cell Sheets Improve Early Biomechanical Graft Strength in Rabbits After Anterior Cruciate Ligament Reconstruction.

BACKGROUND: Although various reconstruction techniques are available for anterior cruciate ligament (ACL) injuries, a long recovery time is required before patients return to sports activities, as the reconstructed ACL requires time to regain strength. To date, several studies have reported use of mesenchymal stem cells in orthopaedic surgery; however, no studies have used adipose-derived stem cell (ADSC) sheets in ACL reconstruction (ACLR). HYPOTHESIS: ADSC sheet transplantation can improve biomechanical strength of the autograft used in ACLR. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 68 healthy Japanese white rabbits underwent unilateral ACLR with a semitendinosus tendon autograft after random enrollment into a control group (no sheet; n = 34) and a sheet group (ADSC sheet; n = 34). At 2, 4, 8, 16, and 24 weeks after surgery, rabbits in each group were sacrificed to evaluate tendon-bone healing using histological staining, micro-computed tomography, and biomechanical testing. At 24 weeks, scanning transmission electron microscopy of the graft midsubstance was performed. RESULTS: The ultimate failure load for the control and sheet groups, respectively, was as follows: 17.2 ± 5.5 versus 37.3 ± 10.3 (P = .01) at 2 weeks, 28.6 ± 1.9 versus 47.4 ± 10.4 (P = .003) at 4 weeks, 53.0 ± 14.3 versus 48.1 ± 9.3 (P = .59) at 8 weeks, 66.2 ± 9.3 versus 95.2 ± 43.1 (P = .24) at 16 weeks, and 66.7 ± 27.3 versus 85.3 ± 29.5 (P = .39) at 24 weeks. The histological score was also significantly higher in the sheet group compared with the control group at early stages up to 8 weeks. On micro-computed tomography, relative to the control group, the bone tunnel area was significantly narrower in the sheet group at 4 weeks, and the bone volume/tissue volume of the tendon-bone interface was significantly greater at 24 weeks. Scanning transmission electron microscopy at 24 weeks indicated that the mean collagen fiber diameter in the midsubstance was significantly greater, as was the occupation ratio of collagen fibers per field of view, in the sheet group. CONCLUSION: ADSC sheets improved biomechanical strength, prevented bone tunnel enlargement, and promoted tendon-bone interface healing and graft midsubstance healing in an in vivo rabbit model. CLINICAL RELEVANCE: ADSC sheets may be useful for early tendon-bone healing and graft maturation in ACLR.

Synoviolin is not a pathogenic factor for auto-inflammatory diseases.

Auto-inflammatory syndromes are rare diseases characterized by arthritis and joint destruction, symptoms similar to but distinct from rheumatoid arthritis (RA). Therapeutic targets have not been well characterized for auto-inflammatory syndromes, although the E3 ligase Synoviolin was previously shown to be a novel therapeutic target for RA. Here, we show that Synoviolin loss has little impact on a model of auto-inflammatory diseases. We previously established such a model, the hIL-1 cTg mouse, in which IL-1 signaling was constitutively activated, and animals exhibit symptoms recapitulating auto-inflammatory syndromes such as major joint dominant arthritis. Here, we crossed hIL-1 cTg with Synoviolin flox'd mice to yield hIL-1 cTg/Synoviolin cKO mice. Synoviolin gene expression was ablated in adult hIL-1 cTg/Synoviolin cKO mice by injection of pIpC to activate Mx1 promoter-driven Cre recombinase. However, symptoms seen in hIL-1 cTg mice such as arthritis and joint destruction were not alleviated by targeting Synoviolin, ruling out Synoviolin as a therapeutic target for auto-inflammatory disease. Our results indicate that although similar, RA and auto-inflammatory diseases are different diseases, and treatment strategies should differ accordingly.

Compressive mechanical stress enhances susceptibility to interleukin-1 by increasing interleukin-1 receptor expression in 3D-cultured ATDC5 cells.

BACKGROUND: Mechanical overload applied on the articular cartilage may play an important role in the pathogenesis of osteoarthritis. However, the mechanism of chondrocyte mechanotransduction is not fully understood. The purpose of this study was to assess the effects of compressive mechanical stress on interleukin-1 receptor (IL-1R) and matrix-degrading enzyme expression by three-dimensional (3D) cultured ATDC5 cells. In addition, the implications of transient receptor potential vanilloid 4 (TRPV4) channel regulation in promoting effects of compressive mechanical loading were elucidated. METHODS: ATDC5 cells were cultured in alginate beads with the growth medium containing insulin-transferrin-selenium and BMP-2 for 6 days. The cultured cell pellet was seeded in collagen scaffolds to produce 3D-cultured constructs. Cyclic compressive loading was applied on the 3D-cultured constructs at 0.5 Hz for 3 h. The mRNA expressions of a disintegrin and metalloproteinases with thrombospondin motifs 4 (ADAMTS4) and IL-1R were determined with or without compressive loading, and effects of TRPV4 agonist/antagonist on mRNA expressions were examined. Immunoreactivities of reactive oxygen species (ROS), TRPV4 and IL-1R were assessed in 3D-cultured ATDC5 cells. RESULTS: In 3D-cultured ATDC5 cells, ROS was induced by cyclic compressive loading stress. The mRNA expression levels of ADAMTS4 and IL-1R were increased by cyclic compressive loading, which was mostly prevented by pyrollidine dithiocarbamate. Small amounts of IL-1ß upregulated ADAMTS4 and IL-1R mRNA expressions only when combined with compressive loading. TRPV4 agonist suppressed ADAMTS4 and IL-1R mRNA levels induced by the compressive loading, whereas TRPV4 antagonist enhanced these levels. Immunoreactivities to TRPV4 and IL-1R significantly increased in constructs with cyclic compressive loading. CONCLUSION: Cyclic compressive loading induced mRNA expressions of ADAMTS4 and IL-1R through reactive oxygen species. TRPV4 regulated these mRNA expressions, but excessive compressive loading may impair TRPV4 regulation. These findings suggested that TRPV4 regulates the expression level of IL-1R and subsequent IL-1 signaling induced by cyclic compressive loading and participates in cartilage homeostasis.

Influence of Patella thickness on Patellofemoral pressure in total knee Arthroplasty.

BACKGROUND: Patellofemoral complications are one of the major issues after total knee arthroplasty (TKA). Excessive patellofemoral joint pressure is associated with complications after TKA surgery, and the amount of patellar osteotomy has a direct effect on patellofemoral joint pressure. The purpose of this study was to evaluate the influence of patella thickness on patellofemoral pressure in TKA. METHODS: Five freshly frozen cadavers were operated with a custom-made Stryker posterior stabilizing type knee joint prosthesis. Patellofemoral joint pressure was measured using a pressure sensor, with the knee joint flexed from 90 to 110 degrees, and with patellar thickness of - 2 mm to + 4 mm. RESULTS: Increasing or decreasing patellar thickness significantly increased or decreased patellofemoral pressure. Regarding knee flexion angle, patellofemoral pressure increased with increasing patellar thickness at all flexion angles, but the pressure increase was greatest at 90 degrees of knee flexion and smallest at 110 degrees. CONCLUSIONS: The amount of patellar osteotomy influences the patellofemoral pressure. Surgeons should avoid increasing patella thickness, since the resulting increased patellofemoral pressure may reduce knee joint function.