Synovial mesenchymal stem cells secrete more lubricin than adipose mesenchymal stem cells after injection into rat osteoarthritis knees.

Intra-articular injection of mesenchymal stem cells (MSCs) is envisioned as a solution for knee osteoarthritis (OA). Although synovial MSCs (SyMSCs) are promising for cartilage regeneration, the clinical choice is usually adipose MSCs (AdMSCs). However, the similarities/differences in the mode of action between SyMSCs and AdMSCs remain unclear. Here, we compared factors secreted by human SyMSCs and AdMSCs after injection into OA knees. Human SyMSCs or AdMSCs were injected into the knees of rat partial meniscectomy models. The next day, the knee joints were collected to analyze the distribution of injected MSCs and transcriptome changes in the human MSCs and rat synovium. Non-injected MSCs were mixed with rat synovium as a control. After injection, no difference was apparent in intra-articular distribution of the SyMSCs or AdMSCs. RNA sequencing demonstrated an enrichment of cytokine-cytokine receptor interaction-related genes in both human SyMSCs and AdMSCs after injection. Differentially expressed genes (DEGs) specific to SyMSCs were associated with cartilage matrix synthesis and homeostasis. PCR analysis of the matrisome-related DEGs showed significantly higher expression of PRG4 in SyMSCs than in AdMSCs after injection. Immunostaining also confirmed a significantly greater expression of lubricin by SyMSCs than by AdMSCs. These findings indicate that SyMSCs will be a more promising treatment for OA.

Biomechanical analysis of load distribution in porcine hip joints at different acetabular coverages.

BACKGROUND: Developmental dysplasia of the hip causes secondary osteoarthritis. Finite element analysis suggests high hip joint contact pressure in patients with hip dysplasia and a reduction in contact pressure after periacetabular osteotomy. However, few biomechanical studies have examined the load distribution in the hip joint. This study aimed to investigate the biomechanical properties of load distribution in porcine hip joints at different acetabular coverages. METHODS: Six porcine hip joints were analyzed using three models: 1) neutral coverage, 2) 15° under-coverage (defined as dysplasia model), and 3) 15° over-coverage created by varying the acetabular coverage. The load distribution was assessed using a pressure-mapping sensor system after applying a loading force of 100 N to the hip joint. RESULTS: In the dysplasia model, the load was concentrated at the acetabular rim; in the neutral and over-coverage models, it was dispersed. The average contact pressure was significantly higher in the dysplasia model than in the neutral coverage model ([0.42 vs. 0.3 MPa]; p = 0.004). The contact area was significantly smaller in the dysplasia model than in the neutral coverage model ([250.7 vs. 345.0 mm2]; p = 0.004). No significant differences were observed in contact pressure or area between the neutral and over-coverage models. CONCLUSIONS: Insufficient acetabular coverage in the dysplasia model demonstrated higher contact pressure and smaller contact area than the neutral model. Conversely, the contact pressure and area in the over-coverage model did not differ significantly from those in the normal model. Therefore, surgeons should note that acetabular coverage overcorrection has limited effect; normalization is crucial during periacetabular osteotomy.

Cartilage thickness in the medial compartment of the knee joint evaluated by MRI three-dimensional analysis correlates with weight-bearing line ratio and joint line convergence angle.

PURPOSE: The correlation between cartilage thickness evaluated by 3D MRI and knee alignment has not been elucidated. The study's purpose was to retrospectively verify whether average cartilage thickness calculated by the automatic MRI 3D analysis system for each subregion was correlated with knee alignment. METHODS: A total of 53 patients underwent medial meniscus repair or high tibial osteotomy for medial knee osteoarthritis. Cartilage thickness was automatically calculated using 3D MRI software. Knee alignment, weight-bearing line ratio (WBLR), joint line convergence angle (JLCA), medial proximal tibial angle (MPTA), and lateral distal femoral angle (LDFA) were calculated on a weight-bearing long-leg radiograph using digital planning software. The association between knee alignment and the average cartilage thickness at 18 subregions in the medial femoral condyle (MFC) and medial tibial plateau (MTP) was evaluated using Spearman's rank correlation coefficient. RESULTS: Cartilage thickness of the MFC had moderately positive correlations with WBLR at four subregions and weak correlations at two subregions. Cartilage thickness of the MTP had moderately positive correlations with WBLR at four subregions. Cartilage thickness of the MFC had moderately negative correlations with JLCA at six subregions. Cartilage thickness of the MTP had moderately negative correlations with JLCA at four subregions and a weak correlation at one subregion. Conversely, cartilage thickness had weak correlations with MPTA or LDFA. CONCLUSIONS: In knees with pathological conditions in the medial compartment, cartilage thicknesses by 3D MRI had positive correlations with WBLR and JLCA at almost all subregions of the MFC and at the anterior-middle and central-external of the MTP. Treatment strategies should be considered in light of these regions. LEVEL OF EVIDENCE: Cross-sectional study (diagnosis); Level of evidence, 2.

Augmentation of a Nonanatomical Repair of a Medial Meniscus Posterior Root Tear With Centralization Using Three Knotless Anchors May Be Associated With Less Meniscal Extrusion and Better Compressive Load Distribution in Mid-Flexion Compared With Non-Anatomical Root Repair Alone in a Porcine Knee Model.

PURPOSE: To investigate the biomechanics of the centralization augmentation using knotless soft anchors to a nonanatomical transtibial pull-out root repair in a porcine medial meniscus posterior root tear (MMPRT) model. METHODS: Porcine knee joints (N = 10) were used to perform one of the following procedures: (1) intact; (2) MMPRT; (3) nonanatomical root repair; (4) nonanatomical root repair with centralization using 2 anchors: anchors were inserted at the posterior medial collateral ligament (MCL) border and 10 mm anterior to the posterior MCL border; and (5) nonanatomical root repair with centralization using 3 anchors: another anchor was placed 10 mm posterior to the posterior MCL border. Contact area on the medial meniscus (MM), contact pressure in the MM and tibial cartilage, and MM extrusion were evaluated at 30°, 45°, 60°, and 90° knee flexions under 200 N compressive force. RESULTS: MM extrusion at the posterior MCL border was significantly reduced after root repair with centralization using 3 anchors than after root repair alone at 30° (-0.063 mm vs 1.5 mm, P = .017), 45° (0.21 mm vs 1.7 mm, P = .018), and 60° (0.78 mm vs 2.3 mm, P = .019). There were no significant differences in MM extrusion between the root repair alone and root repair with centralization using 2 anchors at all flexion angles. The contact area in the middle and posterior MM was significantly greater after centralization with 3 anchors than after root repair alone at all flexion angles (except the posterior MM at 90°). The mean contact pressure in the tibial cartilage was significantly lower after centralization with 3 anchors than after root repair at all angles. CONCLUSIONS: Augmentation of a nonanatomical repair of a medial meniscus posterior root tear with centralization using three knotless anchors may be associated with less meniscal extrusion and better compressive load distribution between 30° and 60° flexion compared with nonanatomical root repair alone in a porcine model. CLINICAL RELEVANCE: This biomechanical study at time zero suggests that the addition of centralization using 3 knotless anchors may reduce MM extrusion and restore the load-distributing function of the MM.

Low central sensitisation inventory score is associated with better post-operative outcomes of osteotomy around the knee.

PURPOSE: The purpose of this study was to investigate the potential association between central sensitisation inventory (CSI) scores and post-operative patient-reported outcomes (PROs) in patients underwent osteotomy around the knee (OAK), with a CSI cut-off score specific for knee osteoarthritis. METHODS: CSI scores were collected from 173 patients who underwent OAK, along with their knee injury and osteoarthritis outcome score (KOOS) and pain numeric rating scale (NRS) scores. Patients were divided into high-CSI score group and low-CSI score group with a cut-off score of 17. Multivariate linear regression was performed to test the association between CSI scores and post-operative outcomes. Pre-surgery KOOS and NRS scores and the rate of attainment of minimal clinically important difference (MCID) of KOOS scores was analysed as secondary outcomes. RESULTS: Low-CSI score group had significantly higher post-operative KOOS scores and lower pain NRS scores compared to the high-CSI score group (< p = 0.01) after adjusting for confounding factors. For pre-operative scores, only the KOOS-Symptom score was significantly different between the groups (64.7 ± 20.1 when CSI < 17 vs.55.1 ± 19.7 when CSI ≥ 17; p = 0.008). The low-CSI score group had significantly higher MCID achievement rates of KOOS-Pain, Symptom, and ADL than the high-CSI score group (86% vs. 68%; 74% vs. 55%; 86% vs. 67%, respectively; P < 0.05). CONCLUSIONS: This study established an association between post-operative CSI scores ≥ 17 and poorer outcomes following OAK, highlighting the potential value of the CSI in identifying patients in need of more comprehensive peri-operative pain management. LEVEL OF EVIDENCE: Level III. Retrospective comparative study.

Simultaneous bilateral total knee arthroplasty is safe and effective for patients in different ages.

BACKGROUND: Simultaneous bilateral total knee arthroplasty is considered beneficial for patients with bilateral end-stage knee osteoarthritis, even though there could be potential postoperative complications. Presently, there is a paucity of evidence of the efficacy and safety of SB-TKA for elderly patients. This study aimed to compare the clinical outcomes of simultaneous bilateral total knee arthroplasty by different age groups. METHODS: A total of 216 knees of 108 patients, who underwent simultaneous bilateral total knee arthroplasty for osteoarthritis at our hospital between April 2015 and September 2018, were divided into three groups based on age: 60s (44 knees), 70s (106 knees), and 80s (66 knees). Perioperative data and postoperative clinical outcomes 1 year after surgery were compared between the age groups. RESULTS: The patients in the Group 60s were characterized by a higher body mass index (BMI) (P < 0.01), a lower pre-operative knee function score (P < 0.01), longer operation time (P < 0.01), greater intra-operative (P < 0.01), and postoperative bleeding (P = 0.026). No significant difference was found in terms of occurrence of various postoperative complications, although deep vein thrombosis and delirium occurred slightly more frequently in the Group 70s and the Group 80s than in the Group 60s group. The Knee Society Knee Score, a function score, and patient satisfaction scores were significantly improved in all groups 1 year after surgery. Moreover, these indexes of clinical outcomes were similar among the three groups. CONCLUSION: Performing simultaneous bilateral total knee arthroplasty in 80s patients was found to be as safe and effective as in the 60s and 70s patients. LEVEL OF EVIDENCE: 3 (A retrospective cohort study).

Mid-term clinical outcomes of a posterior stabilized total knee prosthesis for Japanese patients: A minimum follow-up of 5 years.

BACKGROUND: A high-flexion posterior-stabilized total knee prosthesis has been developed for the Asian population. The component design was based on computed tomography images of Japanese osteoarthritic knees. The femoral component is composed of zirconia ceramics, which exhibit low friction and high durability. The present study aimed to evaluate the mid-term clinical outcomes of this implant. METHODS: This study included 334 knees of 210 patients who underwent primary total knee arthroplasty with this implant at our hospital between October 2010 and December 2014. The patients comprised 28 men and 172 women with an average age of 73 years. The average follow-up period was 5.9 years, and the follow-up rate was 71.1%. Clinical outcomes were assessed using the Knee Society scoring system, 2011 Knee Society questionnaire, and Knee Injury and Osteoarthritis Outcome Score. Kaplan-Meier survivorship analysis was performed to determine the cumulative prosthesis survival rate. RESULTS: In terms of clinical outcomes at the final follow-up, the average ranges of motion were -2.0 in extension and 126.7 in flexion. The Knee Society knee and function scores were 94.2% and 72.6%, respectively. With revision surgery or radiographic failure for any reason as the endpoint, the survival rates at 5 and 9 years were 98.2% and 95.5%, respectively. The most common reason for revision surgery or radiological failure was aseptic loosening. CONCLUSIONS: Despite several revision cases mainly due to aseptic loosening, the present study found that this new high-flexion posterior-stabilized total knee arthroplasty prosthesis design showed comparable results for Asian populations with other PS prosthesis. LEVELS OF EVIDENCE: Level Ⅱ (Prospective cohort study).

Medial Tibial Osteophyte Width Strongly Reflects Medial Meniscus Extrusion Distance and Medial Joint Space Width Moderately Reflects Cartilage Thickness in Knee Radiographs.

BACKGROUND: The presence of medial tibial osteophytes on knee radiographs suggests cartilage wear, but may be associated with medial meniscus extrusion (MME). The joint space width of the medial compartment consists anatomically of cartilage and the medial meniscus, but which is most responsible for joint space narrowing remains unclear. Magnetic resonance imaging (MRI) reveals MME and cartilage thickness. PURPOSES: To determine which radiographic medial tibial osteophyte width correlates better with cartilage thickness or MME distance and which radiographic medial joint space width correlates better with cartilage thickness or MME distance. STUDY TYPE: Cross-sectional. POPULATION: Total of 527 subjects, 253 females and 274 males, aged 30-79 years, included in the Kanagawa Knee Study. FIELD STRENGTH/SEQUENCE: 3 T/fat-suppressed spoiled gradient echo and proton density weighted. ASSESSMENT: The medial tibial osteophyte width and "the minimum joint space width at the medial compartment" (mJSW) were measured from plain radiographs. The cartilage region was automatically extracted from MRI data using software. The medial femoral and tibial cartilage regions were each divided into nine subregions, and the average thickness of the cartilage was determined in each region and subregion. MME was manually measured by two orthopedic surgeons using MRI coronal section images. STATISTICAL TESTS: Pearson's correlation coefficient and their comparison, with P < 0.05 considered statistically significant. RESULTS: The absolute values of the correlation coefficients were 0.33 at maximum between osteophyte width and cartilage thickness and 0.76 between osteophyte width and MME; the value was significantly higher with MME than with cartilage thickness (P < 0.001). The absolute values of the correlation coefficients were 0.50 at maximum between mJSW and cartilage thickness and 0.16 between mJSW and MME; the value was significantly higher with cartilage thickness than with MME (P < 0.001). DATA CONCLUSION: The medial tibial osteophyte width strongly reflected MME and the medial joint space width moderately reflected cartilage thickness. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 3.

Difference in the joint space of the medial knee compartment between full extension and Rosenberg weight-bearing radiographs.

OBJECTIVES: Radiographs are the most widespread imaging tool for diagnosing osteoarthritis (OA) of the knee. Our purpose was to determine which of the two factors, medial meniscus extrusion (MME) or cartilage thickness, had a greater effect on the difference in the minimum joint space width (mJSW) at the medial compartment between the extension anteroposterior view (extension view) and the 45° flexion posteroanterior view (Rosenberg view). METHODS: The subjects were 546 participants (more than 50 females and 50 males in their 30 s, 40 s, 50 s, 60 s, and 70 s) in the Kanagawa Knee Study. The mJSW at the medial compartment was measured from both the extension and the Rosenberg views, and the "mJSW difference" was defined as the mJSW in the Rosenberg view subtracted from the mJSW in the extension view. The cartilage region was automatically extracted from MRI data and constructed in three dimensions. The medial region of the femorotibial joint cartilage was divided into 18 subregions, and the cartilage thickness in each subregion was determined. The MME was also measured from MRI data. RESULTS: The mJSW difference and cartilage thickness were significantly correlated at 4 subregions, with 0.248 as the highest absolute value of the correlation coefficient. The mJSW difference and MME were also significantly correlated, with a significantly higher correlation coefficient (0.547) than for the mJSW difference and cartilage thickness. CONCLUSIONS: The MME had a greater effect than cartilage thickness on the difference between the mJSW at the medial compartment in the extension view and in the Rosenberg view. KEY POINTS: • The difference in the width at the medial compartment of the knee between the extension and the flexion radiographic views was more affected by medial meniscus extrusion than by cartilage thickness.

Second-look arthroscopy after meniscus repair and synovial mesenchymal stem cell transplantation to treat degenerative flaps and radial tears of the medial meniscus: A case report.

BACKGROUND: The purpose of this study was to compare arthroscopic findings of a degenerative flap and radial tear of the medial meniscus (MM) before and one year after treatment by meniscus repair and synovial mesenchymal stem cell (MSC) transplantation. METHODS: Patients with a degenerative flap and radial MM tear that would generally be treated by meniscectomy were included. The patients ranged in age from 45 to 62 years and all underwent meniscus repair and synovium harvest at time 0. The digested synovium was cultured with autologous serum for 12 days, and an average of 4 × 107 MSCs were transplanted at two weeks. A second-look arthroscopy was performed at 52 weeks (n = 6). The average duration of symptoms was 24 months. For flap tears, arthroscopic findings were quantified in terms of the presence, stability, and smoothness of the meniscus at each zone and area. The Lysholm score was evaluated throughout the 52 week follow-up. RESULTS: Four patients with MM flap tears showed deficiencies in the central area at the posterior junctional zone before treatment, but this zone was completely restored to a stable and smooth condition in two patients and partially restored in the other two patients. The arthroscopy score for a flap tear at the central area of the posterior junctional zone was 0.3 ± 0.5 before treatment and 4.3 ± 2.1 after treatment. The score was significantly higher after treatment (p < 0.05, n = 4). The original radial MM tears in two patients were healed one year after treatment. Lysholm scores were significantly higher at 4 and 52 weeks after treatment than before treatment (n = 6). CONCLUSIONS: Arthroscopic findings for a degenerative flap and radial tear of the MM were improved at the central area of the posterior junctional zone one year after meniscus repair and MSC transplantation.

Trends in arthroplasty in Japan by a complete survey, 2014-2017.

BACKGROUND: Precise knowledge of the prevalence and trends of arthroplasty can facilitate the design of medical plans for efficient treatments. The National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) Open Data Japan provides statistics about the annual number of arthroplasties (knee, hip, shoulder, finger, elbow, and foot/ankle) through health insurance claim numbers for these surgeries. The purpose of this study was to document the annual arthroplasty numbers between 2014 and 2017 in Japan and to analyze their four-year trends, gender differences, age distributions, and regional differences as revealed by the complete survey. METHODS: Numbers of arthroplasty surgeries were extracted from the NDB Open Data Japan for 2014-2017. For "knee", "hip", "shoulder", "finger", "elbow", and "foot/ankle" arthroplasties, we showed the annual arthroplasty numbers, annual arthroplasty numbers by age group, annual arthroplasty numbers in individual prefectures, and annual arthroplasty numbers per 100,000 population in individual prefectures. RESULTS: The annual arthroplasty numbers in 2017 were 146,189 for all joints, 82,304 for knees, 59,029 for hips, 2454 for shoulders, 1551 for fingers, 536 for elbows, and 291 for feet/ankles. For the four years up to 2017, the rate of alteration in the number of arthroplasties was +14% for total arthroplasties, +9% for knees, +21% for hip joints, +97% for shoulders, + 8% for fingers, -10% for elbows, and +25% for feet/ankles. The proportion of females was 70-90% and the peak age was between the late 60s and late 70s for all joints. Variations in arthroplasty numbers per population by prefecture appeared to be small for knees and hips and large for other joints. CONCLUSIONS: We revealed the annual total number of arthroplasties for each joint in Japan using the NDB Open Data Japan for the first time.

Characteristics of MSCs in Synovial Fluid and Mode of Action of Intra-Articular Injections of Synovial MSCs in Knee Osteoarthritis.

We have been studying mesenchymal stem cells (MSCs) in synovial fluid and the intra-articular injection of synovial MSCs in osteoarthritis (OA) knees. Here, mainly based on our own findings, we overview the characteristics of endogenous MSCs in the synovial fluid of OA knees and their mode of action when injected exogenously into OA knees. Many MSCs similar to synovial MSCs were detected in the synovial fluid of human OA knees, and their number correlated with the radiological OA grade. Our suspended synovium culture model demonstrated the release of MSCs from the synovium through a medium into a non-contacting culture dish. In OA knees, endogenous MSCs possibly mobilize in a similar manner from the synovium through the synovial fluid and act protectively. However, the number of mobilized MSCs is limited; therefore, OA progresses in its natural course. Synovial MSC injections inhibited the progression of cartilage degeneration in a rat OA model. Injected synovial MSCs migrated into the synovium, maintained their MSC properties, and increased the gene expressions of TSG-6, PRG-4, and BMP-2. Exogenous synovial MSCs can promote anti-inflammation, lubrication, and cartilage matrix synthesis in OA knees. Based on our findings, we have initiated a human clinical study of synovial MSC injections in OA knees.

Morphological changes in synovial mesenchymal stem cells during their adhesion to the meniscus.

Synovial mesenchymal stem cells (MSCs) are an attractive cell source for transplantation because of their high chondrogenic potential, especially in areas like the meniscus of the knee. A synovial MSC suspension placed onto the meniscus for 10 min promoted healing of repaired meniscal tears that generally do not heal. Here, we quantified the proportion of human synovial MSCs that adhered to a porcine abraded meniscus, clarified their morphological changes, and revealed the mechanism by which the synovial MSCs adhered to the meniscus. The numbers of adhering cells at immediately after 10, 60 min and 6, 24 h after suspension placement were calculated. The meniscus surface was examined by scanning electron microscopy, and 50 cells were randomly selected at each time period, classified, and quantified for each of the six donors. Approximately 28% of the synovial MSCs immediately adhered to the meniscus after placement and the proportion of adhered cells increased further with time. All cells maintained a round shape for 60 min, and then transformed to a mixture of round and semi-flattened cells. By 24 h, flattened cells covered the meniscus. Microspikes were observed in 36% of the floating synovial MSCs and in 76% of the cells on the meniscus shortly after placement on the meniscus, then the proportion of cells with pseudopodia increased. The bleb-dominant cell proportion significantly decreased, and the smooth-dominant cell proportion increased within 60 min. Microspikes or the bodies of synovial MSCs were trapped by meniscal fibers immediately after placement. The proportion of adhered cells increased with time, and the cell morphology changed dynamically for 24 h as the synovial MSCs adhered to the meniscus. The MSCs in the round morphological state had a heterogeneous morphology. The microspikes, and the subsequent development of pseudopodia, may play an important role in adhesion onto the meniscus.

The effect of a centralization procedure for extruded lateral meniscus on load distribution in porcine knee joints at different flexion angles.

BACKGROUND: Meniscal extrusion results in loss of the ability to resist hoop strain and biomechanical overload on the joint articular surface. A centralization technique has been developed to overcome these problems. In this study, we analyzed the biomechanics of the extruded and centralized lateral meniscus (LM) in porcine knee joints at different flexion angles. METHODS: Porcine knee joints (n = 8) were set in the universal tester and each knee was tested under the following states: 1) intact; 2) extrusion-meniscal extrusion was created by resecting the posterior root of the LM and posterior synovial capsule; and 3) centralization-centralization was performed by two anchors inserted in the lateral tibial plateau. Deviation distance of the meniscus, contact pressure, and contact area in the anterior LM, middle LM, posterior LM, and the contact pressure of the tibial cartilage were evaluated with an axial compressive force of 200 N at knee flexion angles of 30°, 45°, 60°, and 90°. RESULTS: The deviation distance of LM significantly increased in extrusion but was restored to the intact status after centralization at all angles. Both the contact pressure and area significantly decreased in extrusion and were restored after centralization close to the intact status in the anterior and middle LM; in the posterior LM, however, decreased contact pressure and area were not restored after centralization. The contact pressure of the tibial cartilage increased significantly in extrusion but decreased close to the intact status after centralization. CONCLUSIONS: This centralization procedure could reduce extrusion of the LM and restore the load-distributing function of the anterior-middle LM. However, the procedure itself could not restore hoop function in cases where the defect lies in the posterior LM.

Relationship between medial meniscus extrusion and cartilage measurements in the knee by fully automatic three-dimensional MRI analysis.

BACKGROUND: We developed a fully automatic three-dimensional knee MRI analysis software that can quantify meniscus extrusion and cartilage measurements, including the projected cartilage area ratio (PCAR), which represents the ratio of the subject's actual cartilage area to their ideal cartilage area. We also collected 3D MRI knee data from 561 volunteers (aged 30-79 years) from the "Kanagawa Knee Study." Our purposes were to verify the accuracy of the software for automatic cartilage and meniscus segmentation using knee MRI and to examine the relationship between medial meniscus extrusion measurements and cartilage measurements from Kanagawa Knee Study data. METHODS: We constructed a neural network for the software by randomly choosing 10 healthy volunteers and 103 patients with knee pain. We validated the algorithm by randomly selecting 108 of these 113 subjects for training, and determined Dice similarity coefficients from five other subjects. We constructed a neural network using all data (113 subjects) for training. Cartilage thickness, cartilage volume, and PCAR in the medial femoral, lateral femoral, medial tibial, and lateral tibial regions were quantified by using the trained software on Kanagawa Knee Study data and their relationship with subject height was investigated. We also quantified the medial meniscus coverage ratio (MMCR), defined as the ratio of the overlapping area between the medial meniscus area and the medial tibial cartilage area to the medial tibial cartilage area. Finally, we examined the relationship between MMCR and PCAR at middle central medial tibial (mcMT) subregion located in the center of nine subregions in the medial tibial cartilage. RESULTS: Dice similarity coefficients for cartilage and meniscus were both approximately 0.9. The femoral and tibial cartilage thickness and volume at each region correlated with height, but PCAR did not correlate with height in most settings. PCAR at the mcMT was significantly correlated with MMCR. CONCLUSIONS: Our software showed high segmentation accuracy for the knee cartilage and meniscus. PCAR was more useful than cartilage thickness or volume since it was less affected by height. Relations ips were observed between the medial tibial cartilage measurements and the medial meniscus extrusion measurements in our cross-sectional study. TRIAL REGISTRATION: UMIN, UMIN000032826 ; 1 September 2018.

Biomechanical analysis of the centralization procedure for extruded lateral menisci with posterior root deficiency in a porcine model.

PURPOSE: The purpose of this study was to investigate the biomechanical properties of load distribution following a centralization procedure for extruded lateral menisci with posterior root deficiency in a porcine model. METHODS: Six porcine knee joints were analyzed in a universal tester, as follows: 1) Intact; 2) Extrusion (meniscus extrusion was created by resecting the posterior root of the lateral meniscus, as well as the posterior synovial capsule); and 3) Centralization (two anchors were inserted at the lateral tibial plateau, and the meniscus was sutured to secure it close to the original position). Meniscus extrusion was evaluated using two markers put on the posterior cruciate ligament and the lateral meniscus, and the load distribution were assessed using a pressure mapping sensor system after applying a loading force of 200 N to the knee joint. RESULTS: Distance between two markers (mm, Average; 95% CI) was larger in the extrusion group (21.9; 17.8, 25.6) than in the intact (18.1; 15.1, 22.7) or the centralization (15.3; 12.9, 18.0) groups. The contact area (mm2) in the middle of the meniscus was significantly smaller in the extrusion group (45.8; 18.5, 73.2) than in the intact (85.7; 72.1, 99.2) or the centralization (98.3; 88.8, 107.8) groups. The maximum contact pressure (MPa) in the tibial plateau was significantly higher in the extrusion group (0.37; 0.35, 0.40) than in the intact (0.29; 0.21, 0.37) or the centralization (0.29; 0.22, 0.36) groups. CONCLUSIONS: The centralization procedure enabled a reduction of the meniscus extrusion in the lateral meniscus with posterior root deficiency and restored the maximum load and contact pressure to values close to those of the normal knee joint.

Cryopreservation in 95% serum with 5% DMSO maintains colony formation and chondrogenic abilities in human synovial mesenchymal stem cells.

BACKGROUND: Synovial mesenchymal stem cells (MSCs) are an attractive cell source for cartilage and meniscus regeneration. The optimum cryopreservation medium has not been determined, but dimethylsulfoxide (DMSO) should be excluded, if possible, because of its toxicity. The purposes of our study were to examine the possible benefits of higher concentrations of serum and the effectiveness of 100% serum (without DMSO) for the cryopreservation of synovial MSCs. METHODS: Human synovium was harvested from the knees of four donors with osteoarthritis during total knee arthroplasty. Synovial MSCs (8 × 105 cells) were suspended in 400 µL medium and used as a Time 0 control. The same number of synovial MSCs was also suspended in 400 µL α-MEM medium containing 10% fetal bovine serum (FBS) (5% DMSO, and 1% antibiotic), 95% FBS (and 5% DMSO), or 100% FBS (no DMSO) and cryopreserved at - 80 °C for 7 days. After thawing, the cell suspensions (1.5 µL; 3 × 103 cells) were cultured in 60 cm2 dishes for 14 days for colony formation assays. Additional 62.5 µL samples of cell suspensions (1.25 × 105 cells) were added to tubes and cultured for 21 days for chondrogenesis assays. RESULTS: Colony numbers were significantly higher in the Time 0 and 95% FBS groups than in the 10% FBS group (n = 24). Colony numbers were much lower in the 100% FBS group than in the other three groups. The cell numbers per dish reflected the colony numbers. Cartilage pellet weights were significantly heavier in the 95% FBS group than in the 10% FBS group, whereas no difference was observed between the Time 0 and the 95% FBS groups (n = 24). No cartilage pellets formed at all in the 100% FBS group. CONCLUSION: Synovial MSCs cryopreserved in 95% FBS with 5% DMSO maintained their colony formation and chondrogenic abilities to the same levels as observed in the cells before cryopreservation. Synovial MSCs cryopreserved in 100% FBS lost their colony formation and chondrogenic abilities.

Comparison of mesenchymal stem cells obtained by suspended culture of synovium from patients with rheumatoid arthritis and osteoarthritis.

BACKGROUND: Mobilization of mesenchymal stem cells (MSCs) from the synovium was revealed using a "suspended synovium culture model" of osteoarthritis (OA). The pathology of rheumatoid arthritis (RA) differs from that of OA. We investigated whether mobilization of MSCs from the synovium also occurred in RA, and we compared the properties of synovial MSCs collected from suspended synovium culture models of RA and OA. METHODS: Human synovium was harvested during total knee arthroplasty from the knee joints of patients with RA (n = 8) and OA (n = 6). The synovium was suspended in a bottle containing culture medium and a culture dish at the bottom. Cells were harvested from the dish and analyzed. RESULTS: No significant difference was observed between RA and OA in the harvested cell numbers per g of synovium. However, the variation in the number of cells harvested from each donor was greater for RA than for OA. The harvested cells were multipotent and no difference was observed in the cartilage pellet weight between RA and OA. The surface epitopes of the cells in RA and OA were similar to those of MSCs. CONCLUSION: Mobilization of MSCs from the synovium was demonstrated using a suspended synovium culture model for RA. The harvested cell numbers, chondrogenic potentials, and surface epitope profiles were comparable between the RA and OA models.

Trends in isolated meniscus repair and meniscectomy in Japan, 2011-2016.

BACKGROUND: Meniscus surgery is the most commonly performed orthopedic surgery, and despite recent emphasis on saving the meniscus, the current status of meniscus surgeries is little known in many countries, including Japan. The National Database of Health Insurance Claims and Specific Health Checkups of Japan and the Statistics of Medical Care Activities in Public Health Insurance track meniscus surgeries through health insurance claims. The National Database provides the numbers for 2014 and 2015, and the Statistics of Medical Care Activities provides the numbers from June 2011 to June 2016. Our aim was to analyze isolated meniscus surgery numbers and meniscus repair ratios by age group based on the National Database and evaluate trends of meniscus repair ratios for the latest six years from the Statistics of Medical Care Activities. METHODS: Meniscus surgeries by age group were counted from the National Database for 2014-2015, and meniscus repair ratios (meniscus repairs/meniscus surgeries) were calculated. The numbers were also counted from the Statistics of Medical Care Activities in 2011-2016. For statistical analysis of annual trends of meniscus repair ratios, the Cochran-Armitage trend test was used. Meniscus surgeries with concomitant knee ligament surgeries were excluded. RESULTS: According to the National Database, isolated meniscus surgeries totaled 34,966 in 2015, with peak ages of patients in their late teens and 60s. The meniscus repair ratio was 19% in 2014 and 24% in 2015. According to the Statistics of Medical Care Activities, the meniscus repair ratio was 9% in 2011 and significantly increased to 25% in 2016 (p = 0.0008). The ratio also increased significantly in each age group between the early 20s and late 70s. CONCLUSIONS: Approximately 35,000 meniscus surgeries are performed in Japan annually, with peak ages in the late teens and 60s. The number of meniscus repairs has increased over the past six years.

[Homeostasis and Disorder of Musculoskeletal System.Transplantation of synovial mesenchymal stem cells for cartilage and meniscus regeneration.]

Cartilage injury remains one of the common clinical problems due to its limited regeneration capacities. Meniscectomy commonly performed for meniscus injury leads to osteoarthritis, but the indication of meniscus repair is limited. We have identified that synovial mesenchymal stem cells(MSCs)are superior to MSCs derived from other tissues in proliferation capacity and in vitro/in vivo chondrogenic potentials. When suspension of synovial MSCs was placed on the cartilage defect for 10 minutes, 60% of the cells attached to the defect site. Based on these basic researches, we started a clinical study for cartilage regeneration by arthroscopic transplantation of synovial MSCs. Additionally, we transplanted synovial MSCs for meniscus injury after meniscus repair. We obtained good clinical results of cartilage regeneration and meniscus healing without any serious side effects. Transplantation of synovial MSCs will be useful for cartilage or meniscus injuries.