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Objective This study aimed to determine whether the intra-articular injection of human adipose-derived mesenchymal stem cells (ADSCs) protects against the progression of murine post-traumatic osteoarthritis. Design ADSCs were isolated from human abdomen or buttock adipose tissues. In in vitro study, ADSCs conditioned medium was added to human chondrocytes pre-treated with interleukin-1β (IL-1β), and resultant gene expression of target inflammatory genes was measured by real-time quantitative polymerase chain reaction. A mouse model of knee osteoarthritis was generated by unilaterally transecting the medial meniscus in the right hind limb of 20 female C57BL/6 mice. Mice were randomly assigned to 2 treatment groups that received 6 µl intra-articular injections of either phosphate-buffered saline (control) or 2 × 104 cells/μl of ADSCs 14, 28, and 42 days post-surgery. Mice were euthanized 84 days post-surgery and histological and micro-computed tomography evaluation of knee joints were analyzed. Hind limb weight-bearing distribution was measured pre-surgery and 28 and 84 days post-surgery. Results Conditioned medium from cultured human adipose-derived mesenchymal stem cells suppressed the expression of target inflammatory genes in chondrocytes pre-treated with IL-1β, suggesting anti-inflammatory properties ( P < 0.01). Histological analyses indicated that the progression of destabilization of medial meniscus-induced knee osteoarthritis was suppressed by the administration of ADSCs compared with control group at medial femorotibial joint in vivo. This protective effect was related to a reduction in articular cartilage loss. Conclusion The intra-articular injection of ADSCs suppressed articular cartilage loss in a mouse model of knee osteoarthritis, possible through anti-inflammatory mechanisms.

We assessed the effects of low-intensity exercise with blood flow restriction (BFR) during rest intervals on recovery of muscle function and pain during exercise and rest intervals.Participants were 10 males and study arms of the participants were randomly assigned into three conditions; low-intensity exercise with BFR during rest intervals (rBFR), low-intensity exercise with BFR during exercise (eBFR) and low-intensity exercise only (EO). The exercise task was elbow flexion until repetition failure at 30% of 1 RM and cuff pressure was 120 mmHg. The maximum voluntary isometric contraction (MVIC) and the muscle endurance (ME) were measured pre, post, 1, 24 and 48 h after the exercise. Pain during exercise and rest intervals were evaluated using the Numerical Rating Scale.MVIC and ME significantly decreased after exercise in all conditions. Pain during exercise was lower in rBFR (4.2 ± 2.9) (p = 0.007) and EO (4.4 ± 2.7) (p = 0.014) conditions compared to eBFR condition (6.7 ± 1.7), but the pain during rest intervals was more intense in rBFR condition (5.2 ± 1.6) compared to eBFR (1.5 ± 1.4) and EO (1.7 ± 1.2) conditions (p 0.001).We discovered that recovery of muscle function was the same as BFR during rest intervals and BFR during exercise. Also, our results suggested that BFR itself may cause the perception of pain. Future studies are thus required to investigate the optimal dosage focusing on the pressure volume and intensity used in BFR during intervals.

Background: This study aimed to translate, adapt, and test the psychometric properties of the Japanese version of the Victorian Institute of sports assessment for patellar tendinopathy (VISA-P-J) according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN).Methods: This prospective cohort study registered 43 participants ≥18 years old with a history of painful symptoms in the inferior pole of the patella to the proximal patellar tendon lasting ≥1 month. Pain in daily life and during sports activities, symptom classification, and patient global impression of change (PGIC) were assessed at the baseline, 1 week, and 12 weeks. The psychometric properties of the VISA-P-J were calculated according to the COSMIN.Results: The intraclass correlation coefficient (ICC)2,1 for test-retest reliability was 0.87 (pConclusion: We demonstrated that the VISA-P-J, based on the COSMIN, was a reliable, valid, and responsive assessment method for individuals with chronic pain in the patellar tendon.

Background This study aimed to validate and determine the minimal clinically important difference (MCID) in the Japanese version of the International Knee Documentation Committee Subjective Knee Form (Japanese IKDC-SKF) for patients with anterior cruciate ligament (ACL) injuries. Methods This prospective study was performed using the COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) guideline to assess the measurement properties of reliability, responsiveness, validity, and interpretability of the Japanese IKDC-SKF. Results A total of 152 patients were enrolled in the study. The Japanese IKDC-SKF had excellent internal consistency [Cronbach's alpha (95% confidence interval, CI) was 0.90 (0.88–0.92), and the test–retest reliability [intraclass correlation coefficient, ICC2,1 (95% CI)] was 0.97 (0.94–0.98). The content validity (r), which was interpretable between the Japanese IKDC-SKF and the Japanese Anterior Cruciate Ligament questionnaire 25 was −0.87 (P Conclusions Our results indicate that the Japanese version of the IKDC-SKF is a reliable, valid, and responsive measurement instrument with which to evaluate the physical function of patients with ACL injuries.

Background/aimsThis study aimed to assess the efficacy and sterility of stored platelet-rich plasma (PRP) eye-drops for corneal epithelial wound healing compared with those of autologous serum (AS) eye-drops.MethodsAt our single institution, PRP and AS eye-drops were prepared using peripheral blood obtained from six healthy volunteers and stored at 4°C. Platelet and leucocyte counts and transforming growth factor (TGF)-β1, epidermal growth factor (EGF), and fibronectin levels were assessed during storage for up to 4 weeks. Sterility was assessed by culturing 4-week poststorage samples. PRP, AS, and phosphate-buffered saline (PBS) eye-drop efficacies were compared using corneal epithelial wound healing assays in vitro and in vivo and monitoring wound areas under a microscope every 3 hours.ResultsHigher platelet and lower leucocyte counts were seen in PRP than in whole blood on the day of preparation. After storage, TGF-β1, EGF, and fibronectin levels were significantly higher in PRP than in AS eye-drops. In vitro and in vivo, PRP eye-drops used on the day of preparation significantly promoted corneal epithelial wound healing compared with PBS. Moreover, PRP eye-drops stored for 4 weeks significantly promoted corneal wound healing compared with PBS and AS eye-drops.ConclusionPRP eye-drops stored at 4°C for 4 weeks promoted corneal epithelial wound healing with higher levels of growth factors than those observed in AS eye-drops, while maintaining sterility, suggesting that this preparation satisfies the unmet medical needs in the treatment of refractory keratoconjunctival epithelial disorders.

Background: Platelet-rich plasma (PRP) has emerged as a treatment for osteoarthritis (OA). However, the effect that leukocyte concentrations in PRP have on OA remains unclear. Purpose: To clarify the optimal PRP formulation for OA treatment by comparing pure PRP, leukocyte-poor PRP (LP-PRP), and leukocyte-rich PRP (LR-PRP) in a rat arthritis model. Study Design: Controlled laboratory study. Methods: Knee arthritis was induced bilaterally in male Wistar rats with intra-articular injections of monosodium iodoacetate (MIA) on day 0. Rats were randomly assigned to 1 of 3 treatment groups (pure PRP, LP-PRP, and LR-PRP). On day 1, allogenic PRP was injected into the right knee of rats and phosphate-buffered saline was injected into the left knee as a control. Weight distribution on the hindlimbs was measured for 14 days to assess pain behavior. Rats were euthanized at day 5 or 14 for histological assessment of synovial tissue and cartilage. Immunohistochemical staining of calcitonin gene-related peptide (CGRP) and α-smooth muscle actin was performed to determine the mechanism of pain relief induced by the PRP preparations. Results: In all groups, PRP increased the load-sharing ratio on PRP-injected knees, with pure PRP eliciting the largest effect among the 3 kinds of PRP ( P < .05). Structural changes in the synovial tissue were significantly inhibited in the pure-PRP group compared with the control group after both 5 and 14 days ( P < .001 and P = .025, respectively), whereas no significant difference was found between the control, LP-PRP, and LR-PRP groups. An inhibitory effect on cartilage degeneration was observed only in the pure-PRP group on day 14. Pure PRP also significantly inhibited expression of CGRP-positive nerve fibers in the infrapatellar fat pad compared with the other groups ( P < .05). Conclusion: In an MIA-induced arthritis model, pure PRP injection was the most effective treatment for reduction of pain-related behavior and inhibition of synovial inflammation and pain sensitization. Clinical Relevance: PRP formulations should be optimized for each specific disease. This study shows the superiority of pure PRP for treatment of arthritis and joint pain.

[Purpose] This study aimed to assess the reliability of the Functional Movement Screen and explore whether this evaluation tool can predict the risks of personal injuries in Japanese soccer players. [Participants and Methods] Seventy-five Japanese college soccer players who participated in our 1 year prospective cohort study underwent a Functional Movement Screen assessment. Demographic data, athletic characteristics, and types and frequency of injuries sustained, were analyzed with the assessment results. [Results] There was no significant difference in the mean Functional Movement Screen composite scores between genders. Although the Functional Movement Screen showed excellent inter-rater reliability (0.92), low overall internal consistency (0.35) was observed. A maximum score of 3 in straight leg raise occurred in 94% of the females and was considered a ceiling effect. None of the cut-off point scores of the Functional Movement Screen were associated with the number of overall injuries, lower limb injuries, and traumatic injuries, or time to return to play. The Functional Movement Screen composite score of ≤15 represented the maximum sensitivity of 76.92% and specificity of 34.78% with 0.56 in the area under the curve. [Conclusion] Functional Movement Screen composite scores do not have sufficient sensitivity and specificity for predicting injuries in Japanese college soccer players.

IntroductionThe elevated cytokine levels in patients suffering from anterior cruciate ligament (ACL) rupture may lead to acute post-traumatic arthritis (APTA) and post-traumatic osteoarthritis (PTOA). Due to its chondrogenerative and anti-inflammatory effect, platelet-rich plasma (PRP) therapy is expected to show a positive outcome in APTA and PTOA. The proposed trial aims to quantitatively measure the efficacy of PRP injection in arresting post-traumatic cartilage degeneration among patients after ACL reconstruction.Methods and analysisThis will be a single-blind, randomised, prospective, controlled clinical trial designed following the Consolidated Standards of Reporting Trials guidelines. After ACL reconstruction, 80 patients will be randomised to receive either leucocyte-poor PRP injection after joint aspiration or a placebo control group receiving only joint aspiration. Participants (age 20–49 years) will be those who have undergone ACL reconstruction within the past 2 weeks with a body mass indexEthics and disseminationThe study was approved by The Independent Ethics Committee for Clinical Trials of the Japanese Association for the Promotion of State-of-the-Art Medicine. Results of the trial and each of the outcomes will be shared via conferences and publication in a peer-reviewed journal.Trial registration numberjRCTb030200391.

There has recently been growing interest worldwide in biological therapies such as platelet-rich plasma injection for the treatment of knee osteoarthritis. However, predicting the effectiveness of platelet-rich plasma therapy remains uncertain. Therefore, this retrospective cohort study was performed to assess a range of predictors for the effectiveness of platelet-rich plasma therapy in treating knee osteoarthritis. The study included 517 consecutive patients who underwent three injections of leucocyte-poor platelet-rich plasma therapy from 2016 to 2019 at a single institution. The treatment outcomes, including patient-oriented outcomes (visual analogue scale score and Knee Injury and Osteoarthritis Outcome Score), were analyzed and compared according to the severity of knee osteoarthritis based on Kellgren–Lawrence (KL) grading using standing plain radiographs. Fisher’s exact test, univariate regression, and multivariate regression were used for data analysis. Patient-oriented outcomes were significantly improved 6 and 12 months after platelet-rich plasma therapy. The overall responder rate in patients who met the Outcome Measures in Rheumatology (OMERACT)–Osteoarthritis Research Society International (OARSI) responder criteria was 62.1%. The responder rate was significantly lower in patients with severe knee osteoarthritis (KL4, 50.9%) than in those with mild (KL2, 75.2%) and moderate (KL3, 66.5%) knee osteoarthritis. The multivariate logistic regression analysis revealed that deterioration of the knee osteoarthritis grade (increased KL grade) was a significant predictor of a worse clinical outcome (odds ratio, 0.58, 95% confidence interval, 0.45–0.75, p &lt, 0.001). The relative risk for non-responders in severe (KL4) KOA was 2.1 (95% CI, 1.5–3.0) at 6 months and 2.3 (1.6–3.2) at 12 months compared with mild-to-moderate (KL2-3) KOA. The efficacy of platelet-rich plasma therapy was not affected by age, sex, body weight, or platelet count. This study revealed that the effectiveness of platelet-rich plasma therapy for the treatment of knee osteoarthritis is approximately 60% and that the effectiveness depends on the severity of knee osteoarthritis. This observation is useful not only for physicians but also for patients with knee osteoarthritis.

Background and purpose Psychological factors including fear of pain, re-injury during movement (kinesiophbia) affect return-to-sport rates after anterior cruciate ligament (ACL) reconstructive surgery. Clinicians often encounter in the daily practice that athletes explain lack of self-confidence or psychological readiness during the sports activity. The Tampa Scale for Kinesiophobia (TSK) has been used to evaluate psychological outcomes in patients with ACL injuries in many countries and translated into Japanese version in 2013. However, no researchers validated its reliability, validity, and responsiveness of TSK for patients with ACL injury up to now. The purpose of this study was to evaluate the measurement properties of the Japanese version of the TSK (TSK-J) in patients with ACL injuries. Study design Cohort study (Diagnostic); Level of evidence, 2. Methods This prospective study was performed in the department of orthopaedic surgery at the university hospital of Juntendo from Sep 2016 and Apr 2017. Patients who diagnosed with ACL injury with or without reconstruction surgery completed several patient-reported outcome measures (PROMs) were included in this study. The COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) guidelines were used to evaluate reliability, validity, responsiveness, and interpretability of the TSK-J. Results 222 patients were included in this study. The TSK-J for ACL injured patients showed good internal consistency (Cronbach’s alpha = 0.79) and excellent test-retest reliability (intra-class correlation coefficient, ICC2,1 = 0.90, 95% CI = 0.81 to 0.95). In addtion, the TSK-J was significantly but moderately correlated with the IKDC-SKF (r = − 0.49, P r = − 0.48, P r = 0.48, P r = − 0.12, P Conclusions Our study demonstrated that the Japanese version of TSK has good reliability. However, its low validity and responsiveness indicate that it may not the best way to assess psychological factors for patients with ACL injury.

Background: The present study investigated the effects of different timings of BFR during HIT on muscle hypertrophy, muscle strength, and pain during exercise.Methods: The study included 14 limbs from seven heathy males. Participants were divided into three groups: BFR during exercise (EX); BFR during rest (RE), and training only (CON). Participants performed elbow flexion exercises by BIODEX, two days / week for eight weeks. BFR was set at 120 mmHg pressure. Elbow flexor peak torque, and muscle cross-sectional area were measured, before and after the training period. The pain during exercise were measured during training.Results: The peak torque was significantly increased the RE and CON (p < 0.05), but no increase was observed in the EX. Exercise repetitions the RE (set 1, 26.5 ± 8.7 reps; set 2, 15.2 ± 8.0 reps; set 3, 13.1 ± 4.7 reps; set 4, 13.8 ± 6.3 reps) decreased two sets earlier than the CON (set 1, 28.0 ± 8.6 reps; set 2, 25.6 ± 7.5 reps; set 3, 24.4 ± 8.2 reps; and set 4, 23.8 ± 7.2 reps) (p < 0.01). The numerical rating scale was higher in the EX during exercise and in the RE during rest compared with the CON. However, the RE did not show exacerbated pain during exercise (p < 0.01).Conclusions: This present study showed that BFR during rest can lead to muscle hypertrophy and muscle strength with fewer exercise repetitions than training only. BFR during rest showed the greatest decreases in peak torque during exercise and did not exacerbate pain during exercise.

Introduction Platelet-rich plasma (PRP) therapy is used to treat pathological conditions such as degenerative inflammatory diseases including osteoarthritis (OA) by enhancing tissue repair and promoting anti-inflammatory effects. Although PRP therapy for patients with knee OA improved pain and functional scores, the association of clinical outcomes and quality of PRP including cell composition and concentration is unclear. Methods Therefore, this study analyzed blood cell counts, including the immature platelet fraction (IPF), in peripheral blood and PRP of 144 patients with knee OA who underwent PRP therapy. The mean leukocyte and platelet concentrations in whole blood and PRP were analyzed using an XN-1000 automated hematology analyzer. Visual analogue scale (VAS) scores and knee injury and osteoarthritis outcome scores (KOOS) before and 1 month after a single PRP injection were also determined. Results Higher platelet and lower leukocyte concentration rates were observed in PRP compared with whole blood. The platelet concentration in whole blood was negatively correlated with VAS improvement. The percentage of IPF (IPF%) in whole blood was positively correlated with VAS improvement and KOOS (pain) improvement, whereas the IPF% in PRP tended to correlate with VAS improvement. Furthermore, multivariate logistic regression demonstrated the high IPF% in whole blood was significantly associated with VAS improvement. The low percentage of neutrophil (neutrophil%) in PRP was significantly associated with the VAS improvement and KOOS (ADL) improvement. Conclusions Therefore, PRP efficacy for OA might depend on the patient's biological status., Highlights • High percentage of IPF (IPF%) in whole blood was significantly associated with VAS improvement. • Low neutrophil% in PRP was significantly associated with VAS improvement and KOOS (ADL) improvement. • The PRP efficacy for knee OA might depend on the patient's biological status.

Purpose Although platelet-rich plasma (PRP) therapy has become an increasingly popular treatment for sports-related injuries, the molecular mechanisms of PRP on tissue healing process remain poorly understood. The aim of the present study was to develop an experimental method quantifying the efficacy of PRP with murine patellar tendon injury model, leading to future elucidation of the mechanisms of PRP on healing processes. Methods Full-thickness defects were created in the central third of the murine patellar tendon. The prepared allogenic PRP gel was applied on the defect of the patellar tendon (PRP group), while the remaining mice served as the untreated control group. Mice were sacrificed at 2, 4, 6, 8, and 10 weeks after the operation, with histological sections obtained in each time point (n = 4 / time point / group). Semi-quantitative histological evaluation was performed in accordance with the Bonar score. The variables included in this scoring system were cell morphology, ground substance, collagen arrangement, and vascularity, with higher grades indicating worse tendon structures. In addition, the ratio of the collagen fibers to the entire tendon tissue (FT ratio) was measured using KS400 software as a quantitative histological evaluation. Results The total Bonar score in the PRP group was significantly lower than in control group. With regard to the variables in the Bonar score, the vascularity score was significantly higher in the PRP group at 2 and 4 weeks, while the collagen arrangement score was significantly lower in the PRP group at 8 weeks. Based on a quantitative evaluation, the recovery speed of the patellar tendon determined by FT ratio was significantly faster in the PRP group than in the control group at 6 and 8 weeks. Conclusions We have developed an experimental method for histological and quantitative evaluation of the effects of PRP on tissue healing using murine patellar tendon injury model. The results of this study suggest that the local application of PRP could enhance the tissue-healing process both directly through action on localized cells and indirectly through the recruitment of reparative cells through the blood flow. Further investigations will be needed to confirm the mechanisms of PRP in tissue-healing processes with the development of this experimental model.

Introduction: Knee osteoarthritis (KOA), the most common form of osteoarthritis (OA) is a considerable health concern worldwide. Platelet-rich plasma (PRP) is a common therapeutic option for KOA. Different types of PRPs have varying efficacies. However, a comparative analysis of the qualities of these PRPs is lacking. Methods: Two types of PRPs, including autologous protein solution (APS), and leukocyte-poor PRP (LP-PRP) along with whole blood (WB) and platelet-poor plasma (PPP) were characterized for platelet content, leukocyte content, and composition in 10 healthy volunteers (HV) (the controlled laboratory study) and 16 KOA patients (a retrospective observational study). Additionally, the levels of the platelet-derived growth factor (PDGF)-BB, and different cytokines were estimated in HV. Results: In HV, the concentrations of platelets and leukocytes, levels of different cytokines, including interleukin 1 receptor antagonist (IL-1Ra), soluble TNF receptor type II (sTNF-RII), and IL-1β, and the ratio of IL-1Ra/IL-1β were significantly higher in APS, whereas the PDGF-BB was higher in LP-PRP than APS. In KOA patients, a higher concentration of platelets was observed in LP-PRP, and a higher concentration of leukocytes was observed in APS than LP-PRP. Following the PAW classification system, LP-PRP was classified as P2-B type in HV (51.3 × 104/μl) and KOA (53.4 × 104/μl), whereas APS was classified as P3-A type in HV (110.1 × 104/μl) and P2-A type in KOA (29.0 × 104/μl). In a retrospective observational study, the KOA patients who underwent APS injection had a higher incidence of arthralgia, and this arthralgia lasted for a longer time than LP-PRP injection in the same individual. Discussion: The quality of the two PRPs differed distinctively depending on their preparation methods, which might affect their clinical efficacies and adverse events. Therefore, the characterization of these parameters should be prioritized while choosing PRP.

Background Platelet-rich plasma (PRP) therapy has become an increasingly popular treatment for orthopaedics and sports-related injuries, and various clinically available PRP preparation methods exist. However, the differences in PRP quality among numerous preparation methods remain unclear. Specifically, the benefit of including leukocytes in the PRP product remains controversial, and few studies have been conducted to evaluate the effects of the interaction between platelets and leukocytes on the growth factor concentrations. The aim of the present study was to compare the biological characteristics of PRPs focusing on the leukocyte concentration and composition. Methods Leucocyte rich (LR)-PRP, leucocyte poor (LP)-PRP, and pure-PRP were prepared from the peripheral blood of 6 healthy male volunteers (mean age: 31.3 years). The concentrations of platelets, leukocytes, erythrocytes, growth factors (transforming growth factor-beta 1: TGF-β1; fibroblast growth factor-basic: FGF-b; platelet-derived growth factor-BB: PDGF-BB; vascular endothelial growth factor: VEGF) and matrix metalloproteinase-9 (MMP-9) from each of the PRP samples were measured. Considering the interaction between platelets and leukocytes, correlations between platelets/leukocytes and growth factors/MMP-9 were analyzed using partial correlation coefficients. Results The platelet concentration did not differ among the three PRP preparation methods. Conversely, the leukocyte concentration was dramatically different: 14.9 ± 4.5 (10 3 /μl) in LR-PRP, 2.4 ± 1.3 (10 3 /μl) in LP-PRP, 0.2 ± 0.2 (10 3 /μl) in pure-PRP. The platelet concentration positively correlated with all growth factors. On the other hand, the leukocyte concentration positively correlated with PDGF-BB and the VEGF concentration, while it negatively correlated with FGF-b. Regarding catabolic factors, the MMP-9 concentration strongly correlated with the leukocyte concentration, while there was no correlation between the platelet and MMP-9 concentrations. Conclusions These findings demonstrate that leukocytes strongly influence the quality of PRPs. Therefore, modifying the PRP preparation method according to the pathology is essential to achieve better clinical results with PRP therapy.

Silicon and phosphorus contents in Pepperbush standard reference material were determined by neutron activation and X-ray fluorescence methods. In neutron activation analysis, β-ray spectra of 32P produced by 31P (n, γ) 32P reaction on Pepperbush and standard samples were measured by a low background β-ray spectrometer. In X-ray fluorescence analysis, the standard samples were prepared by mixing the Pepperbush powder with silicon dioxide and diammonium hydrogenphosphate. Characteristic X-rays from the samples were analyzed by a wavelength dispersive X-ray fluorescence spectrometer. From the β and X-ray intensities, silicon and phosphorus contents in Pepperbush were determined to be 1840±80 and 1200±50μg g-1, respectively.