Presoaking Grafts in Vancomycin Does Not Impair Graft-Bone Healing in a Rat Anterior Cruciate Ligament Reconstruction Model.

BACKGROUND: The vancomycin presoaking technique (wherein grafts are treated with a vancomycin solution [VS] for anterior cruciate ligament reconstruction [ACLR]) reduces the infection rate after ACLR. However, the effects of this technique on graft-bone healing have not been fully elucidated. PURPOSE: To investigate the effects of vancomycin presoaking on graft-bone healing in a rat ACLR model. STUDY DESIGN: Controlled laboratory study. METHODS: Long flexor digitorum longus tendons were obtained from 9 Wistar rats, and each was randomly allocated to the normal saline (NS) or VS groups. The grafts were immersed in sterile saline for 30 minutes in the NS group and in a 5-mg/mL VS in the VS group. The presence of time-zero graft bacterial contamination was confirmed, and the grafts were incubated in Fluidised Thioglycollate Broth for 2 weeks. ACLR was performed on the right knees of 65 male Wistar rats using the flexor digitorum longus tendons. Each graft was similarly treated. Biomechanical testing, micro-computed tomography, and histological evaluations were performed 4 and 12 weeks postoperatively. RESULTS: The VS group showed significantly reduced graft contamination at time zero (P = .02). The mean maximum loads to failure were 13.7 ± 8.2 N and 11.6 ± 4.8 N in the NS and VS groups, respectively, at 4 weeks (P = .95); and 23.2 ± 13.2 N and 30.4 ± 18.0 N in the NS and VS groups, respectively, at 12 weeks (P = .35). Regarding micro-computed tomography, the mean bone tunnel volumes were 3.76 ± 0.48 mm3 and 4.40 ± 0.58 mm3 in the NS and VS groups, respectively, at 4 weeks (P = .41); and 3.51 ± 0.38 mm3 and 3.67 ± 0.35 mm3 in the NS and VS groups, respectively, at 12 weeks (P = .54). Histological semiquantitative examination revealed no clear between-group differences at any time point. CONCLUSION: Presoaking grafts in vancomycin in a rat ACLR model demonstrated no discernible adverse effects on short- and midterm biomechanical, radiological, and histological investigations. CLINICAL RELEVANCE: The findings provide guidance for surgeons when considering this technique.

Analysis of survivorship following periacetabular osteotomy for hip dysplasia based on three-dimensional acetabular coverage.

Periacetabular osteotomy (PAO) is an established procedure for correcting acetabular coverage and preventing osteoarthritis progression in hip dysplasia. However, it is unclear how acetabular coverage changes three-dimensionally after PAO and how it affects survival. Therefore, this study aimed to investigate the change in three-dimensional acetabular coverage preoperatively and postoperatively and identify demographic, clinical and radiographic factors associated with conversion to total hip arthroplasty (THA) and radiographic osteoarthritis progression after PAO. We retrospectively reviewed 46 consecutive patients (66 hips) who underwent PAO, using preoperative and postoperative radiographs and pelvic computed tomography (CT). Three-dimensional acetabular coverage based on CT data was investigated. Kaplan-Meier survival analysis was performed, and hazard ratios were calculated using univariate Cox regression models to identify the risk factors associated with conversion to THA and radiographic osteoarthritis progression after PAO as the endpoints. Radiographic osteoarthritis progression was defined as a minimum joint space of <2.0 mm. The mean follow-up was 10.7 years. Post-PAO, acetabular coverage gradually increased from the anterosuperior to the superior to the posterosuperior direction. The survival rate after PAO was 98.0% at 10 years. Less postoperative superior acetabular coverage, with a hazard ratio of 0.93, was significantly associated with conversion to THA and radiographic osteoarthritis progression after PAO (P = 0.03). In this study, poor superior acetabular coverage after PAO was a significant risk factor for conversion to THA and radiographic progression of osteoarthritis. Therefore, surgeons should attempt to prioritize the correction of the superior acetabular coverage when performing PAO.

Time elapsed from definitive diagnosis to surgery for osteonecrosis of the femoral head: a nationwide observational study in Japan.

OBJECTIVES: This study documents the time elapsed from the diagnosis of osteonecrosis of the femoral head (ONFH) to surgery, exploring the factors that influence ONFH severity. DESIGN: Retrospective observational study of a nationwide database. SETTING: The Kaplan-Meier method with log-rank tests was applied to examine the period from definitive diagnosis of ONFH to surgery using any surgery as the end point. For bilateral cases, the date of the first surgery was the endpoint. PARTICIPANTS: This study included 2074 ONFH cases registered in 34 university hospitals and highly specialised hospitals of the multicentre sentinel monitoring system of the Japanese Investigation Committee between 1997 and 2018. MAIN OUTCOME MEASURE: The primary outcome was the time from diagnosis to surgery. The secondary outcome was the proportion of subjects remaining without surgery at 3, 6 and 9 months, and at 1, 2 and 5 years after diagnosis. RESULTS: The median time to surgery was 9 months (IQR 4-22 months) after diagnosis of ONFH. The time to surgery was significantly shorter in the alcohol alone group and the combined corticosteroid and alcohol group than in the corticosteroid alone group (p=0.018 and p<0.001, respectively), in early stage ONFH with no or mild joint destruction (stages II and III, p<0.001), and with joint preserving surgery (p<0.001). The proportion without surgery was 75.8% at 3 months, 59.6% at 6 months, 48.2% at 9 months, 40.5% at 1 year, 22.2% at 2 years and 8.3% at 5 years. CONCLUSION: ONFH has been considered to be an intractable disease that often requires surgical treatment, but the fact that surgery was performed in more than half of the patients within 9 months from diagnosis suggests severe disease with a significant clinical impact. TRIAL REGISTRATION NUMBER: Chiba University ID1049.

Characteristics of the synovial microenvironment and synovial mesenchymal stem cells with hip osteoarthritis of different bone morphologies.

BACKGROUND: Variations in bone morphology in patients with hip osteoarthritis (HOA) can be broadly categorized into three types: atrophic, normotrophic, and hypertrophic. Despite the investigations examining clinical elements, such as bone morphology, pain, and range of motion, our understanding of the pathogenesis of HOA remains limited. Previous studies have suggested that osteophytes typically originate at the interface of the joint cartilage, periosteum, and synovium, potentially implicating synovial mesenchymal stem cells (SMSCs) in the process. This study aimed to investigate the potential factors that drive the development of bone morphological features in HOA by investigating the characteristics of the synovium, differentiation potential of SMSCs, and composition of synovial fluid in different types of HOA. METHODS: Synovial tissue and fluid were collected from 30 patients who underwent total hip arthroplasty (THA) with the variable bone morphology of HOA patients. RNA sequencing analysis and quantitative reverse transcription-polymerase chain reaction (RT-qPCR) were performed to analyse the genes in the normotrophic and hypertrophic synovial tissue. SMSCs were isolated and cultured from the normotrophic and hypertrophic synovial tissues of each hip joint in accordance with the variable bone morphology of HOA patients. Cell differentiation potential was compared using differentiation and colony-forming unit assays. Cytokine array was performed to analyse the protein expression in the synovial fluid. RESULTS: In the RNA sequencing analysis, 103 differentially expressed genes (DEGs) were identified, predominantly related to the interleukin 17 (IL-17) signalling pathway. Using a protein-protein interaction (PPI) network, 20 hub genes were identified, including MYC, CXCL8, ATF3, NR4A1, ZC3H12A, NR4A2, FOSB, and FOSL1. Among these hub genes, four belonged to the AP-1 family. There were no significant differences in the tri-lineage differentiation potential and colony-forming capacity of SMSCs. However, RT-qPCR revealed elevated SOX9 expression levels in synovial tissues from the hypertrophic group. The cytokine array demonstrated significantly higher levels of CXCL8, MMP9, and VEGF in the synovial fluid of the hypertrophic group than in the normotrophic group, with CXCL8 and MMP9 being significantly expressed in the hypertrophic synovium. CONCLUSION: Upregulation of AP-1 family genes in the synovium and increased concentrations of CXCL8, MMP9, and VEGF were detected in the synovial fluid of the hypertrophic group of HOA patients, potentially stimulating the differentiation of SMSCs towards the cartilage and thereby contributing to severe osteophyte formation.

Increased bone resorption that outpaces increased bone formation: An important pathology of rapidly destructive coxarthrosis.

Rapid joint destruction caused by rapidly destructive coxarthrosis (RDC) can increase surgical complexity and intraoperative blood loss. This single-center retrospective study investigates osteoporosis-related biomarkers for early RDC diagnosis and explores new treatment targets. We included 398 hip joints from patients who underwent total hip arthroplasty, examining medical records for preoperative patient demographics, bone mineral density of the hip and lumbar spine from dual-energy X-ray absorptiometry scans, and osteoporosis-related biomarkers including TRACP-5b, total P1NP, intact parathyroid hormone, and homocysteine. We compared RDC and osteoarthritis (OA) patients, and univariate analysis showed that RDC patients were older (p < 0.001) and had lower serum levels of albumin (p < 0.001) and higher serum levels of TRACP-5b, total P1NP (p < 0.001), and homocysteine (p = 0.006). Multivariable analysis showed that the ratio of serum TRACP-5b to total P1NP had a more significant difference in RDC patients than in OA patients (p = 0.04). Serum TRACP-5b levels were negatively correlated with the time between RDC onset and blood collection, and Japanese Orthopedic Association pain score. Receiver operating characteristic curve analysis revealed that the ratio of serum TRACP-5b to total P1NP had the highest area under the curve value. This study is the first to demonstrate that the ratio of serum TRACP-5b to total P1NP-increased bone resorption that outpaces increased bone formation-is significantly elevated in patients with RDC and that TRACP-5b is higher in the early stages of RDC. Inhibiting serum levels of TRACP-5b, activated osteoclasts, during early RDC may suppress disease progression.

Stabilization and compensation strategy of the hip angle during gait in hip-osteoarthritis patients from the perspective of whole-body movement synergy.

BACKGROUND: The implementation of a strategy to control the hip angle during gait is important to avoid disease progression in patients with hip osteoarthritis (OA). RESEARCH QUESTION: Do patients with hip OA tend to stabilize their hip angles by a combination of whole-body movements during gait in terms of variability? METHODS: A public gait dataset comprising 80 asymptomatic participants and 106 patients with hip OA was used. Uncontrolled manifold analysis was performed using the joint angles as elemental variables and the hip joint angles as performance variables. The synergy index ΔV, variances of elemental variables that did not affect the performance variable (VUCM) and of those that affected the performance variable (VORT), and index of covariation strategy (COV) were calculated in sagittal and frontal plane. A one-sample t-test for statistical parametric mapping (SPM) analysis was used for ΔV and COV. Two-sample t-tests of SPM analyses were used for ΔV, VUCM, and VORT to compare the two groups. RESULTS: In both planes, the ΔV and COV were significantly larger than zero in both groups (p < 0.001). In the sagittal plane, the VORT was higher in the hip OA group than in the control group after 77 % of stance phase. In the frontal plane, the hip OA group had larger ΔV and VUCM after last half and last quartile of stance phase compared to the control group, respectively. The VORT was smaller in the hip OA group than in the control group. SIGNIFICANCE: The hip angle was stabilized in the hip OA group in the frontal plane but insufficiently stabilized in the sagittal plane; however, the patients changed their hip angle during the early phase of stance. The combination of whole-body movements contributed to the stabilization of hip angle.

Association of osteoporosis and high serum homocysteine levels with intraoperative periprosthetic fracture during total hip arthroplasty: a propensity-score matching analysis.

INTRODUCTION: Intraoperative periprosthetic fracture, one of the most frequent complications of total hip arthroplasty, is a very important factor that affects rehabilitation, hospitalization time, and cost of treatment. Osteoporosis is common in total hip arthroplasty patients and likely contributes to the increasing incidence of periprosthetic fracture. Despite this awareness, preoperative and postoperative osteoporosis evaluations remain insufficient. The purpose of this study was to evaluate the relationships between the occurrence of intraoperative periprosthetic fractures and both bone mineral density (BMD) and osteoporosis-related biomarkers. MATERIALS AND METHODS: This single-center retrospective study included a total of consecutive 487 hip joints of patients with a mean age of 65.5 ± 11.8 years who underwent total hip arthroplasty between July 2017 and December 2020. Patients with low BMD defined as T-score < -1.0 versus those with normal BMD were matched by a 1:1 propensity score to balance for patient baseline characteristics, and outcome was analyzed by a modified Poisson regression model. Our primary outcome was the incidence of intraoperative periprosthetic fracture during surgery. We also investigated the effect modification of osteoporosis-related biomarkers, including tartrate-resistant acid phosphatase 5b (TRACP-5b), total procollagen type 1 amino-terminal propeptide (total P1-NP), intact parathyroid hormone (intact PTH), and homocysteine, on osteoporosis and outcomes. RESULTS: After matching, 250 patients were analyzed. The risk of fracture was significantly higher in patients with low BMD than in normal BMD patients (Incidence rate ratio 5.00 [95% CI 1.11-22.43], p = 0.036). We also observed significant effect of high serum homocysteine on the occurrence of intraoperative fractures (Incidence rate ratio 8.38 × 106 [95% C; 3.44 × 106-2.01 × 107], p < 0.01). CONCLUSION: Preoperative osteoporosis and high serum homocysteine levels were risk factors for intraoperative periprosthetic fractures. LEVEL OF EVIDENCE: III, A single-center retrospective study.

Therapeutic effect of C-type natriuretic peptide on persistent pain in a rat knee arthritis model.

BACKGROUND: Intra-articular injection of C-type natriuretic peptide (CNP) at the acute inflammatory stage suppressed fibrotic changes in the infrapatellar fat pad (IFP), articular cartilage degeneration, and persistent pain in a monoiodoacetic acid (MIA)-induced rat knee arthritis model. In this study, we administered CNP during the inflammation subsiding period to evaluate CNP effectiveness in knees with osteoarthritis (OA) pathology. METHODS: 20 male Wistar rats were randomly divided into two groups. The rats received an intra-articular injection of MIA solution in the right knee to induce inflammation-induced joint degeneration. One group subsequently received an intra-articular CNP injection for six consecutive days from day 8, whereas another group received vehicle solution. Pain avoidance behavior tests and histological analyses were conducted to examine the therapeutic effects of CNP. RESULTS: The incapacitance test indicated that the percent weight on the ipsilateral limb decreased after MIA injection by day 4 and continued to decrease until the end of the experiment in the vehicle group, suggesting persistent pain in the knee. Intra-articular injection of CNP reversed the weight-bearing ratio on day 19. Histological evaluation showed that the CNP group had more residual fat tissue in the IFP and fewer calcitonin gene-related peptide-positive nerve endings compared to the vehicle group. CNP could not reverse articular cartilage degeneration. CONCLUSIONS: Intra-articular injection of CNP after the IFP fibrosis onset had no significant effect on OA severity and extent. Nevertheless, CNP might be utilized therapeutically for OA treatment since it can alleviate persistent knee pain and inhibit structural changes in residual fat tissue.

Hyaluronic acid sheet transplantation attenuates infrapatellar fat pad fibrosis and pain in a rat arthritis model.

Fibrosis of the infrapatellar fat pad (IFP) occurs after knee joint surgery or during knee osteoarthritis (KOA) and causes persistent pain and limited mobility. Previous studies demonstrated that treating IFP fibrosis alleviated pain in animal models. In this study, we examined the effects of hyaluronic acid (HA) sheet transplantation on IFP fibrosis and articular cartilage degeneration in a monoiodoacetic acid (MIA) rat arthritis model (95 male rats). Rats received bilateral intra-articular MIA injections (1.0 mg/30 µL) and underwent surgery 4 days later. HA sheets were transplanted on the right knee of each rat (HA group), with the left knee receiving sham surgery (sham group). Incapacitance tests were performed at multiple time points up to 28 days after MIA injection. Macroscopic, histological, and immunohistochemical analyzes were performed 14 and 28 days after injection. The concentrations of HA and interleukin-1ß (IL-1ß) in the synovial fluid were measured using ELISA. Transplantation of HA sheets could alleviate persistent pain 10-28 days after injection. The HA sheets inhibited articular cartilage degeneration at 14 days. Fibrosis and the invasion of calcitonin gene-related peptide-positive nerve fiber endings in the IFP were inhibited at both 14 and 28 days. Moreover, the HA sheets remained histologically until 10 days after transplantation. The concentration of HA reached its peak on Day 10 after transplantation; the concentration of IL-1ß in the sham group was significantly higher than that in the HA group on Day 7. Therefore, HA sheets could be a promising option to treat IFP fibrosis occurring in KOA and after knee joint surgery.

Wear rate and osteolysis in two types of second-generation annealed highly cross-linked polyethylene in total hip arthroplasty: A retrospective comparative study with a minimum of five years.

BACKGROUND: As no previous study has directly compared the linear wear rate in two types of second-generation annealed highly cross-linked polyethylene, we performed a retrospective study with a minimum of 5-year follow-up to assess primary arthroplasties in the (1) wear rates and (2) incidence of osteolysis of the two types of HXLPE. HYPOTHESIS: There was no significant difference in the linear wear rate and the incidence of osteolysis between the two types of second-generation annealed highly cross-linked polyethylene. PATIENTS AND METHODS: In this single-center study, we reviewed 257 cases of primary cementless total hip arthroplasties between 2011 and 2015, which were performed with 32mm delta ceramic on second-generation annealed highly cross-linked polyethylene (X3 and E1 were used in 105 and 103 cases, respectively.). The mean wear rate was evaluated using a computer-assisted method, and the incidence of osteolysis was evaluated based on the appearance of a localized area with loss of trabecular bone or cortical erosion adjacent to the implants during the latest follow-up. RESULTS: In total, we evaluated 208 cases, followed postoperatively for over 5 years (mean, 6.1 years, range: 5.0-8.0). There were no significant differences between the two groups with respect to age (list in order of Group X, Group E, p value) (61.2±12.3, 62.7±12.1, p=0.36), sex (ratio of male: 17.1%, 14.6%, p=0.61), body mass index (22.9±3.7, 22.8±4.0, p=0.91), pre- (49.9±14.8, 48.5±13.8, p=0.49) and post-operative (91.3±9.1, 92.7±7.0, p=0.23) Japanese Orthopaedic Association Hip Score, cup size (50.8±3.0, 50.9±2.2, p=0.70), cup inclination (38.7±4.8, 37.6±4.8, p=0.10), and cup anteversion (18.7±6.9, 18.5±7.6, p=0.80). The mean linear wear rates of the X3 and E1 groups were 0.057±0.039 (range: 0-0.16) and 0.054±0.037mm/year (range: 0-0.15), respectively (p=0.61). No osteolysis was found on the final plain radiographs in both groups. DISCUSSION: This study revealed that both types of highly cross-linked polyethylene have excellent linear wear rates and were equally safe to use. However, the difference between the two materials in terms of the long-term wear rate should be further validated. LEVEL OF EVIDENCE: III; retrospective case control study.

Comparison of Clinical Outcomes after Revision Anterior Cruciate Ligament Reconstruction using a Bone-patellar Tendon-bone Autograft and that Using a Double-Bundle Hamstring Tendon Autograft.

PURPOSE: The purpose of this study was to compare clinical outcomes between revision anterior cruciate ligament reconstruction (ACLR) using a bone-patellar tendon-bone (BPTB) autograft and that using a double-bundle hamstring tendon (HT) autograft. METHODS: Consecutive cases of revision ACLRs were reviewed. The Lysholm knee scale and Knee Osteoarthritis Outcome Score (KOOS) were recorded at the final follow-up. The pivot shift test, Lachman test, and anterior knee laxity measurement using an arthrometer were evaluated before revision ACLR and at final follow-up. Contralateral knee laxity was also evaluated, and side-to-side differences noted. The Lysholm knee scale, KOOS, the pivot shift test, Lachman test, and anterior knee laxity were compared between HT versus BPTB autograft recipient groups using the Mann-Whitney test or the t-test. RESULTS: Forty-one patients who underwent revision ACLR and followed up for at least 2 years were included. The graft source was a BPTB autograft in 23 patients (BPTB group) and a double-bundle HT autograft in 18 patients (HT group). The mean postoperative follow-up period was 44 ± 28 months in the BPTB group and 36 ± 18 in the HT group (p = 0.38). The HT group had significantly higher KOOS in the pain subscale (less pain) than the BPTB group at the final follow-up (BPTB group 84.2 vs. HT group 94.4; p = 0.02). The BPTB group showed significantly smaller side-to-side difference in anterior knee laxity (superior stability) than the HT group (0.3 vs. 2.6 mm; p < 0.01). The percentage of patients with residual anterior knee laxity in the BPTB group was significantly lower than that in the HT group (9.5% vs. 46.7%; odds ratio, 8.3; p = 0.02). STUDY DESIGN: This was a level 3 retrospective study. CONCLUSION: Revision ACLR with a BPTB autograft was associated with superior results regarding restoration of knee joint stability as compared with that with a double-bundle HT autograft, whereas double-bundle HT autograft was superior to BPTB autograft in terms of patient-reported outcomes of pain. The rest of the patient-reported outcomes were equal between the two groups.

Short-Term Outcomes after High Tibial Osteotomy Aimed at Neutral Alignment Combined with Arthroscopic Centralization of Medial Meniscus in Osteoarthritis Patients.

The study aimed to improve the long-term outcomes of open-wedge high tibial osteotomy (OWHTO); procedures combining OWHTO aimed at neutral alignment and arthroscopic centralization for meniscal extrusion have been introduced. The present study evaluated short-term patient-reported outcome measures; namely, the patient subjective satisfaction scores and Numeric Rating Scale (NRS) for walking pain after OWHTO aimed at neutral alignment with and without arthroscopic centralization for an extruded medial meniscus. A retrospective review of 50 primary OWHTO patients was conducted. Thirty-nine patients were included in the analysis after applying the exclusion criteria. The centralization group included 21 patients with knee osteoarthritis patients who underwent the OWHTO with arthroscopic meniscal centralization, while the control group included 18 patients who underwent OWHTO alone. The patient subjective satisfaction scores and NRS for walking pain were recorded at outpatient visits from before surgery to 3 years after surgery. In terms of the Lysholm knee scale, International Knee Documentation Committee subjective score, and Knee Osteoarthritis Outcome Score, the latest data (at least 2 years after surgery) were reviewed. Radiographic changes in joint space width and joint line congruence angle were measured 2 years postoperatively. Patient demographic data were also reviewed. One patient in the centralization group experienced a superficial surgical site infection. The patient subjective satisfaction and NRS scores for walking pain gradually improved by 1 year after surgery and were sustained until 3 years after surgery in both groups, with no significant difference between the groups. The course of patient-reported outcome measures from before surgery to 3 years after surgery for solely OWHTO aimed at neutral alignment and OWHTO aimed at neutral alignment with arthroscopic centralization showed the similar trends.

The prevalence and treatment of osteoporosis in patients undergoing total hip arthroplasty and the levels of biochemical markers of bone turnover.

AIMS: Osteoporosis is common in total hip arthroplasty (THA) patients. It plays a substantial factor in the surgery's outcome, and previous studies have revealed that pharmacological treatment for osteoporosis influences implant survival rate. The purpose of this study was to examine the prevalence of and treatment rates for osteoporosis prior to THA, and to explore differences in osteoporosis-related biomarkers between patients treated and untreated for osteoporosis. METHODS: This single-centre retrospective study included 398 hip joints of patients who underwent THA. Using medical records, we examined preoperative bone mineral density measures of the hip and lumbar spine using dual energy X-ray absorptiometry (DXA) scans and the medications used to treat osteoporosis at the time of admission. We also assessed the following osteoporosis-related biomarkers: tartrate-resistant acid phosphatase 5b (TRACP-5b); total procollagen type 1 amino-terminal propeptide (total P1NP); intact parathyroid hormone; and homocysteine. RESULTS: The prevalence of DXA-proven hip osteoporosis (T-score ≤ -2.5) among THA patients was 8.8% (35 of 398). The spinal osteoporosis prevalence rate was 4.5% (18 of 398), and 244 patients (61.3%; 244 of 398) had osteopenia (-2.5 < T-score ≤ -1) or osteoporosis of either the hip or spine. The rate of pharmacological osteoporosis treatment was 22.1% (88 of 398). TRACP-5b was significantly lower in the osteoporosis-treated group than in the untreated group (p < 0.001). CONCLUSION: Osteoporosis is common in patients undergoing THA, but the diagnosis and treatment for osteoporosis were insufficient. The lower TRACP-5b levels in the osteoporosis-treated group - that is, osteoclast suppression - may contribute to the reduction of the postoperative revision rate after THA.Cite this article: Bone Joint Res 2022;11(12):873-880.

Effect of CD44 signal axis in the gain of mesenchymal stem cell surface antigens from synovial fibroblasts in vitro.

Tissue-residing mesenchymal stromal/stem cells (MSCs) have multipotent characteristics that are important for adult tissue homeostasis and tissue regeneration after injury. We previously reported that fibroblastic cells isolated from the synovial membrane in the knee joint give rise to cells with MSC characteristics in a two-dimensional culture. To explore the molecular mechanisms underlying these hyperplastic properties, we performed time-course surface antigen expression analyses during in vitro culture. Cells freshly isolated from the synovial membrane rarely contained cells that met the criteria (CD45-CD73+CD90+CD105+). However, the number of cells expressing MSC antigens increased on day 7. Flow cytometric analysis indicated that cells positive for either CD73 or CD90 were specifically derived from cells positive for CD44. CD44 expression was upregulated during culture, and CD105+ cells were specifically derived from the CD44 highly expressing cells. In addition, depletion of hyaluronic acid (HA), a major ligand of CD44, decreased the number of CD105+ cells, whereas supplementation with HA increased their number. These data suggest that intracellular signals activated by CD44 play an important role in the formation and/or maintenance of MSCs.

Short cytoplasmic isoform of IL1R1/CD121a mediates IL1ß induced proliferation of synovium-derived mesenchymal stem/stromal cells through ERK1/2 pathway.

Objectives: IL1ß enhances proliferation of synovial mesenchymal stem/stromal cells (synMSCs) although they don't express its receptor, IL1R1/CD121a, on the cell surface. This study was aimed to elucidate the underlying mechanisms of IL1ß-mediated growth promotion. Methods: Human synMSCs were isolated from the suprapatellar synovial membrane. Cell proliferation was measured by MTT. Flowcytometric analyses were performed for surface antigen expression. Intracellular signaling pathway was analyzed by western blotting, immunocytochemistry and Q-PCR. Results: IL1ß enhanced proliferation through IL1R1/CD121a because IL1 receptor antagonist (IL1Ra) completely inhibited it. Expression analyses indicated that a short isoform of IL1R1/CD121a is expressed in synMSCs. Immunocytochemistry indicated that IL1R1/CD121a was majorly localized to the cytoplasm. Western blotting indicated that IL1ß induced delayed timing of the ERK1/2 phosphorylation and IκBα degradation in synMSCs. Q-PCR analyses for IL1ß-target genes indicated that cyclin D was specifically downregulated by a MAPK/ERK inhibitor, U0126, but not by a NFκB inhibitor, TPCA-1. In contrast, the expression of inflammatory cytokines such as IL1α and IL6 are significantly decreased by TPCA-1 but less effectively decreased by U0126. Conclusion: Our data indicated that the cytoplasmic IL1R1/CD121a transduced IL1ß signal in synMSCs. And the growth-promoting effect of IL1ß can be separated from its inflammatory cytokine-inducing function in synMSCs.

Short stature and short distance between the anterior acetabular rim to the femoral nerve are risk factors for femoral nerve palsy following primary total hip arthroplasty using the modified Watson-Jones approach.

BACKGROUND: Nerve palsy following total hip arthroplasty (THA) critically impacts patient clinical function. However, few studies have focused on femoral nerve palsy (FNP) following THA via the modified Watson-Jones approach. Previous reports have suggested that THA, regardless of the approach, is associated with several FNP risk factors, including female gender, hip dysplasia, revision surgery, and short stature. Magnetic resonance imaging (MRI) has suggested that a shorter distance between the femoral nerve and the anterior acetabular edge (dFN) is related to FNP after THA. The purposes of this study were: 1) to determine the presumed risk factors through a retrospective investigation of FNP clinical courses, and 2) to identify the relationships between FNP occurrence and the short dFN following primary THA via the modified Watson-Jones approach. HYPOTHESIS: Short stature is a risk factor for femoral nerve palsy following THA. i.e. a significant difference in dFN exists between patients with and without FNP. PATIENTS AND METHODS: This retrospective case-control study was performed at a single university hospital. From January 2016 to December 2020, 676 THAs were performed via the modified Watson-Jones approach at our institution. These included 495 THAs performed in the supine position and 181 in the lateral position. In this study, FNP was defined as weakness of the quadriceps femoris (manual muscle test

Difference in tapered wedge stem alignment between supine and lateral position in cementless total hip arthroplasty via modified Watson-Jones anterolateral approach.

BACKGROUND: Whether different body positions during surgery affect postoperative stem alignment in total hip arthroplasty (THA) remains unclear. The purpose of this study was to clarify differences in tapered wedge stem alignment between supine and lateral positions in THA under the modified Watson-Jones anterolateral approach. METHODS: We reviewed 242 consecutive, primary cementless THAs performed with ceramic-on-cross-linked polyethylene via the modified Watson-Jones approach in either supine or lateral positions between 2009 and 2015 (supine group: 113 cases; lateral group: 129 cases). No specific reasons to select supine or lateral positions for the surgery were given during the study period. Computed tomography was performed pre- and postoperatively to measure preoperative femoral anteversion and postoperative stem anteversion, respectively. Stem alignment in coronal and sagittal planes was also evaluated. RESULTS: Mean difference in stem anteversion and femoral anteversion was 8.6 ± 9.4 in the supine position and 13.0 ± 11.4 in the lateral position (p = 0.0013). Although no significant difference was seen between groups for stem alignment in the coronal plane, flexed implantation was more likely in the supine group (46/113, 40.7%) than in the lateral group (20/129, 15.5%). A significant correlation was found between femoral anteversion and stem anteversion in both the supine and lateral groups (r = 0.68, p < 0.0001 and r = 0.52, p < 0.0001, respectively). CONCLUSION: Although stem anteversion was more strongly correlated with femoral anteversion in the supine position than in the lateral position, neutral position in the sagittal plane was more likely to be found with the lateral position than with the supine position. Surgeons can achieve ideal stem positioning by considering these results in the modified Watson-Jones approach in both the supine and lateral positions.

Periprosthetic fragility fracture of the femur after primary cementless total hip arthroplasty.

OBJECTIVES: Periprosthetic bone fragility due to stress shielding (SS) can be a risk factor of periprosthetic fracture after cementless total hip arthroplasty (THA). We aimed to obtain epidemiological information on periprosthetic fragility fracture of the femur (PPFF) after THA. METHODS: We retrospectively reviewed the medical records of 1062 hips that had undergone cementless THA. We evaluated the epidemiological data as well as the features of PPFFs. RESULTS: Of the 1062 hips, 8 (0.8%) were diagnosed with PPFFs. The survival rates, with the occurrence of PPFF as the end point, were 99.2% and 97.6% at 10 and 16 years postoperatively, respectively. When patients were classified as having either mild or severe SS on radiographs 5 years postoperatively, there was no significant difference in the survival rate, with PPFF as the end point. CONCLUSIONS: In our cases, the incidence of PPFF after cementless THA was 0.8%.

Extracellular vesicles derived from mesenchymal stromal cells mediate endogenous cell growth and migration via the CXCL5 and CXCL6/CXCR2 axes and repair menisci.

BACKGROUND: Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) are promising candidates for tissue regeneration therapy. However, the therapeutic efficacy of MSC-EVs for meniscus regeneration is uncertain, and the mechanisms underlying MSC-EV-mediated tissue regeneration have not been fully elucidated. The aims of this study were to evaluate the therapeutic efficacy of intra-articular MSC-EV injection in a meniscus defect model and elucidate the mechanism underlying MSC-EV-mediated tissue regeneration via combined bioinformatic analyses. METHODS: MSC-EVs were isolated from human synovial MSC culture supernatants via ultrafiltration. To evaluate the meniscus regeneration ability, MSC-EVs were injected intra-articularly in the mouse meniscus defect model immediately after meniscus resection and weekly thereafter. After 1 and 3 weeks, their knees were excised for histological and immunohistochemical evaluations. To investigate the mechanisms through which MSC-EVs accelerate meniscus regeneration, cell growth, migration, and chondrogenesis assays were performed using treated and untreated chondrocytes and synovial MSCs with or without MSC-EVs. RNA sequencing assessed the gene expression profile of chondrocytes stimulated by MSC-EVs. Antagonists of the human chemokine CXCR2 receptor (SB265610) were used to determine the role of CXCR2 on chondrocyte cell growth and migration induced by MSC-EVs. RESULTS: In the meniscus defect model, MSC-EV injection accelerated meniscus regeneration and normalized the morphology and composition of the repaired tissue. MSC-EVs stimulated chondrocyte and synovial MSC cell growth and migration. RNA sequencing revealed that MSC-EVs induced 168 differentially expressed genes in the chondrocytes and significantly upregulated CXCL5 and CXCL6 in chondrocytes and synovial MSCs. Suppression of CXCL5 and CXCL6 and antagonism of the CXCR2 receptor binding CXCL5 and CXCL6 negated the influence of MSC-EVs on chondrocyte cell growth and migration. CONCLUSIONS: Intra-articular MSC-EV administration repaired meniscus defects and augmented chondrocyte and synovial MSC cell growth and migration. Comprehensive transcriptome/RNA sequencing data confirmed that MSC-EVs upregulated CXCL5 and CXCL6 in chondrocytes and mediated the cell growth and migration of these cells via the CXCR2 axis.

Inflammatory and healing environment in synovial fluid after anterior cruciate ligament reconstruction: Granulocytes and endogenous opioids as new targets of postoperative pain.

BACKGROUND: Biological processes after anterior cruciate ligament reconstruction (ACLR) is crucial for recovery. However, alterations in the of synovial fluid cell population during the acute phase following ACLR and the relationship between these cells and postoperative pain is unclear. The goal of this study was to reveal alterations in synovial fluid cell population during the acute phase following ACLR and relationship between postoperative pain and proportion of synovial fluid cells. METHODS: Synovial fluids were obtained from all patients (n = 50) before surgery and from patients who showed hydrarthrosis at days 4 (n = 25), and 21 (n = 42) post-surgery. The cell population was analyzed by flow cytometry. IL1ß, IL8, and met-enkephalin in synovial fluid were quantitated by enzyme-linked immunosorbent assay. Patients answered numerical rating scale (NRS) questionnaire at 4 days and approximately 4 weeks postoperatively. RESULTS: The granulocyte population was significantly higher at 4 days after surgery than at any other time points. The population of macrophages was 3.2 times and 7.7 times as high as at surgery on days 4 and 21, respectively. T cell population was significantly higher 21 days after surgery compared to 4 days after surgery. All NRS 4 weeks after surgery showed a significant negative correlation with the granulocyte population in synovial fluid 4 days after surgery. Granulocyte population in synovial fluid significantly correlated with the levels of IL1ß and IL8. Postoperative pain at rest tended to decrease with an increase in met-enkephalin concentration 4 days after ACLR. CONCLUSIONS: Synovial fluid after ACLR had an inflammatory environment at early time points and a healing environment in the subsequent phase about concerning to the cellular composition. A proportion of synovial fluid cells and endogenous opioids affected postoperative pain.