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Neurodegenerative disorders (NDs) are characterized by a gradual loss of neurons and functions that eventually leads to progressive neurological impairment. In view of the heavy burden on the healthcare system, efficient and reliable biomarkers for early diagnosis and therapeutic treatments to reverse the progression of NDs are in urgent need. There has been an increasing interest in using exosomal miRNAs as biomarkers or targeted therapies for neurological diseases recently. In this review, we overviewed the updated studies on exosomal miRNAs as biomarkers and potential therapeutic approaches in NDs, as well as their association with the pathophysiology of this group of disorders, especially Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD). The exosomal miRNAs that are commonly dysregulated across different NDs or are commonly used as therapeutic candidates were also identified and summarized. In summary, the feasibility of exosomal miRNAs as biomarkers and potential targeted therapy for NDs has been verified. However, due to the limitations of existing studies and the discrepancies across different studies, high quality laboratory and clinical investigations are still required.

OBJECTIVE To assess the clinical results of the "figure-of-eight" suture-button technique in the arthroscopic treatment of anterior cruciate ligament (ACL) tibial avulsion fractures. METHODS This was a retrospective study reviewing data from September 2013 to June 2019. A total of 27 patients (13 males and 14 females) who underwent arthroscopic "figure-of-eight" suture-button fixation for displaced ACL avulsion fractures were analyzed. The mean age of the patients in the sample was 15.8 years (10-29 years), with a mean follow-up of 24 months (6-48 months). According to Meyers-McKeever classification, 11 patients were classified as type III and 16 as type IV. All patients were evaluated following the guidelines of the radiological union, the Lysholm knee scoring scale, and the International Knee Documentation Committee (IKDC). RESULTS Fractures were united within 3 months after surgery in all 27 cases. During the last follow-up, all the anterior drawer and Lachman tests were negative, except in 1 patient whose anterior drawer test was 1° positive. The range of motion was improved from 72.22° ± 27.92° before surgery to 137.78° ± 7.38° at the last follow-up (P

Background Femoral avulsion fracture of the posterior cruciate ligament (PCL) in association with meniscus tear is extremely rare in children, and similar cases are not available in the existing literature. Case presentation In this paper, we present a case of a 9-year-old boy treated by an arthroscopic repair technique using two transfemoral tunnels sparing the epiphyseal plate for 8-shaped suture fixation of femoral avulsion fracture of the PCL and using the Fastfix repair system for a meniscus tear. At 3-month postoperative, the boy showed satisfactory recovery with a full range of motion of the right knee and normal muscular strength, and no complications were observed after operation. The patient had been followed up for 24 months and his final assessment demonstrated stable painless knee with excellent functional outcome. In view of this, we suggest that the "figure-of-eight" suture technique using two transfemoral tunnels sparing the epiphyseal plate can be considered a new choice for the treatment of the PCL femoral attachment avulsion, especially in skeletally immature patients. In addition, six similar cases were found in a comprehensive literature review targeting femoral avulsion fracture of the PCL. According to the relevant findings and cases studies, we proposed a new classification named "Xiangya" which might facilitate future clinical decision making.

BackgroundTo evaluate the clinical outcomes of arthroscopic tight fibrous band release in the treatment of adult moderate-to-severe gluteal fibrosis using anterior and posterior portals during mid-term follow-up.MethodsThe data of 138 patients (58 males, 80 females) aged between 18 and 42 years (mean, 28.6 years), presenting with bilateral moderate-to-severe gluteal fibrosis (GF) from October 2013 to August 2019, was retrospectively analyzed. All patients underwent arthroscopic tight fibrous band release using anterior and posterior portals with radiofrequency energy. Under arthroscopic guidance through the posterior portal, we debrided the fatty tissue overlying the contracted band of the gluteal muscle and excised the contracted bands using a radiofrequency device introduced through the anterior portal. The pre- and post-operative gluteal muscle contracture disability (GD) scale and the patient satisfaction rate were compared to evaluate the curative effect of the operation.ResultsThe average operation time was 18 min (range, 10–30 min) and the average blood loss was 4 ml (range, 2–10 ml) for unilateral arthroscopic release. Two cases of post-operative minimal hematomas, 2 cases of bruising and 2 cases of local subcutaneous edema were observed as early complications and were cured by conservative treatment. After surgery, all incisions healed in stage I, and no other complications such as wound infection, nerve and blood vessel injury were detected. One hundred eighteen patients were followed up for 6 to 72 months (mean, 36 months). No lateral instability of the hip was observed and all patients returned to normal gait. The degree of adduction of the hip joint in all these 118 patients was significantly improved relative to their pre-operative conditions. One hundred fifteen patients (97.5%) were able to crouch with knees close to each other after surgery. One hundred fourteen patients (96.6%) were able to cross the affected leg completely without any support. The GD scale was improved from 55.5 ± 10.6 before operation to 90.1 ± 5.2 at the last follow-up (p ConclusionArthroscopic tight fibrous band release using anterior and posterior portals is minimally invasive for adult moderate-to-severe gluteal fibrosis, with a high success rate, quick recovery after surgery and reliable medium-term effect.

Background This study aimed to compare the arthroscopic internal drainage of popliteal cysts alone or in combination with cyst wall resection in terms of clinical outcomes. Methods Forty-two consecutive patients with symptomatic popliteal cysts received arthroscopic treatment. Specifically, 20 of them received arthroscopic internal drainage (AI group) alone and 22 received arthroscopic internal drainage combined with cyst wall resection (AICR group) through double posteromedial portals. Magnetic resonance imaging (MRI) was performed to identify recurrence of popliteal cysts. The Lysholm score and Rauschning-Lindgren grade were used to assess the clinical outcomes. The median of the follow-up period was 24 months (12–48 months). Results The two groups (AI group and AICR group) were similar in age, gender, cyst diameter, associated joint disorder, preoperative Lysholm score, preoperative Rauschning-Lindgren grade and follow-up period (P > 0.05). Relative to the AI group, the AICR group had a significantly prolonged operation time (P P P P P > 0.05). According to the MRI results, the cyst disappeared in 11 (55%), shrank in size in 6 (30%) and existed in 3 (15%) patients in the AI group, and was absent in 18 (81.8%) and shrank in size in 4 (18.2%) patients in the AICR group, suggesting a significant difference between the two (P Conclusion Additional resection of cyst wall can result in a lower recurrence rate of cysts but extend the operation time and increase the incidence of perioperative complications compared with arthroscopic internal drainage of popliteal cysts alone.

This study aimed to examine the associations of dietary magnesium (Mg) intake and serum Mg concentration with the high-sensitivity C-reactive protein (hsCRP) level in early radiographic knee osteoarthritis (OA) patients.Multivariable logistic regression was used to test the associations of dietary and serum Mg with the serum hsCRP in early radiographic knee OA patients after adjustment of a number of potential confounding factors.A total of 936 early radiographic knee OA patients were included. A significant association between dietary Mg intake and hsCRP was observed. The multivariable-adjusted odds ratio (OR) (95% CI) for elevated hsCRP (≥3.0 mg/l) in the second, third, fourth, and fifth dietary Mg intake quintile were 0.44 (95% CI: 0.24-0.82), 0.58 (95% CI: 0.31-1.10), 0.34 (95% CI: 0.15-0.77), and 0.19 (95% CI: 0.06-0.57), respectively, compared with the lowest (first) quintile, and p for trend was 0.01. A significant association between serum Mg concentration and hsCRP was observed. The multivariable-adjusted OR (95% CI) for elevated hsCRP in the second, third, fourth, and fifth serum Mg concentration quintile were 0.63 (95% CI: 0.35-1.12), 0.83 (95% CI: 0.50-1.39), 0.53 (95% CI: 0.31-0.91), and 0.46 (95% CI: 0.25-0.85), respectively, compared with the lowest quintile, and p for trend was 0.01.The present study indicated that both dietary and serum Mg were inversely associated with serum hsCRP in early radiographic knee OA patients.

The purpose of this study was to examine the cross-sectional association between dietary soy milk intake and the prevalence of radiographic knee joint space narrowing (JSN) and osteophytes (OST). Soy milk intake was assessed using a validated semiquantitative food frequency questionnaire and classified into three categories: never

The aim of the study is to examine the cross-sectional associations between dietary antioxidants (carotenoid, vitamin C, E, and selenium) intake and radiographic knee osteoarthritis (OA). A total of 4685 participants were included in this study. Dietary intake was assessed using a validated semi-quantitative food frequency questionnaire. Radiographic knee OA was defined as Kellgren-Lawrence (K-L) grade 2 in at least one leg. A multivariable logistic analysis model was established to test the relationship between dietary antioxidants (carotenoid, vitamin C, E, and selenium) intake and radiographic knee OA with adjustment of a number of potential confounding factors. A significant positive association between dietary vitamin C intake (P value for trend was 0.04 in multivariable adjusted analysis) and radiographic knee OA was observed. The relative odds of radiographic knee OA were increased by 0.39 times in the third quintile (OR 1.39, 95 % CI 1.11-1.73), 0.42 times in the fourth quintile (OR 1.42, 95 % CI 1.13-1.79), and 0.33 times in the fifth quintile (OR 1.33, 95 % CI 1.03-1.71). However, radiographic knee OA was not significantly associated with dietary carotenoid, vitamin E, and selenium. Among dietary antioxidants, dietary vitamin C intake was positively correlated with the prevalence of radiographic knee OA, while no significant association was found between dietary intake of carotenoid, vitamin E, and selenium and the prevalence of radiographic knee OA.

Previous studies have demonstrated that osteopontin (OPN) levels are elevated in the synovial fluid and articular cartilage, and are associated with the severity of knee osteoarthritis (OA). However, the role of OPN in the pathogenesis of OA has yet to be elucidated. The present study aimed to investigate the effects of OPN on the expression of the aggrecanases, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)4 and ADAMTS5, in human OA chondrocytes, as they serve a key function in aggrecan degradation. Human OA chondrocytes were obtained from the knees of 16 patients with OA, and subsequently cultured in a monolayer. The chondrocytes were divided into three groups, which included the control (no treatment), N-OPN (treated with 100 ng/ml OPN, the normal circulating OPN concentration) and the H-OPN groups (treated with 1 µg/ml OPN, a high OPN concentration). Reverse transcription-quantitative polymerase chain reaction was performed to quantify the relative mRNA expression levels of ADAMTS4, ADAMTS5 and aggrecan in the chondrocytes. The mRNA expression levels of ADAMTS4 were significantly reduced in the N-OPN and H-OPN groups when compared with the control group (P0.05). Furthermore, the mRNA expression levels of aggrecan were higher in the N-OPN and H-OPN groups when compared with the control group (P

This study aimed to: (1) examine whether the association between posterior tibial slope and noncontact ACL injury exists in Chinese population; (2) compare the reliability and consistency of the three methods (longitudinal axis, posterior and anterior tibial cortex axis) in lateral radiograph. Case–control study contained 146 patients in total (73 noncontact ACL injuries and 73 meniscus injuries, matched for age and gender), which were verified by arthroscopy, MRI and physical examination. For the total population and the male subgroup, the mean posterior tibial slope of the ACL-injured group was significantly higher than that of the control group (P

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint swelling, joint tenderness, and destruction of synovial joints, leading to severe disability and premature mortality. RA is a multifactorial disease with genetic, environmental, and stochastic components related to its susceptibility. It has been demonstrated that the expression of osteopontin (OPN) is upregulated in the RA patients. Numerous studies have indicated that the full-length OPN or even OPN fragments, such as thrombin-cleaved OPN and its receptors, play the key roles in RA pathogenesis. Therapeutic application of siRNA to target OPN or neutralizing antibodies related to OPN epitopes in RA animal models are in progress, and some results are encouraging. However, there is a long way to go along with the clinical trials. This review focuses on the recent development in research associated with the OPN role in the pathogenesis of RA and provides insights concerning the OPN targeting as therapeutic approaches for patients with RA.

Tissue inhibitors of metalloproteinases (TIMPs) regulate the activity of matrix metalloproteinases (MMPs) and enzymes from the a disintegrin and metalloproteinase domain with thrombospondin motifs family in osteoarthritis (OA). Elevated osteopontin (OPN) levels in plasma, synovial fluid and articular cartilage are associated with progressive OA joint damage; however, the role of OPN in the pathological changes of knee OA remains undetermined. The present study was undertaken to examine the effect of OPN on the expression of TIMP-1 and TIMP-2 mRNA in chondrocytes from 16 patients with knee OA. In this study, following the stimulation of human chondrocytes with recombinant human OPN (rhOPN; 100 ng/ml and 1 μg/ml, respectively) for 48 h, MTT assay was used to determine cell viability while the quantitative polymerase chain reaction (PCR) was used to detect the alterations in TIMP-1 and TIMP-2 levels. The results illustrated that neither 100 ng/ml nor 1 μg/ml rhOPN caused cytotoxicity or apoptosis of chondrocytes and that the relative mRNA expression of TIMP-1 and TIMP-2 was significantly increased in the 1 μg/ml rhOPN group compared with that in the control group (P=0.022 and P=0.003, respectively). However, no significant difference in expression was revealed between the 100 ng/ml rhOPN and control groups (P=0.998 and P=0.209, respectively). In conclusion, OPN may have a protective effect against pathological changes in advanced-stage OA.

SummaryObjectiveWe undertook this study to determine whether thrombin-cleaved osteopontin (OPN) in synovial fluid (SF) represents a useful marker of osteoarthritis (OA) progression in the posterior cruciate ligament transection (PCLT) OA rabbit model.MethodPCLT was performed on the right knee joints of 48 rabbits. The rabbits were then sacrificed separately at 4, 8, 16, and 24 weeks post-surgery, when the joint was harvested and macroscopic and histological assessments of articular cartilage were performed. Thrombin-cleaved OPN product in SF was determined using Western blotting and the levels were measured using an enzyme-linked immunoassay.ResultsThe macroscopic and histological scores for PCLT knees were already elevated 4 weeks after surgery and increased with time. Western blotting showed the presence of thrombin-cleaved OPN in SF from PCLT knees. Thrombin-cleaved OPN levels in SF were elevated at 4 weeks (P

Vasoactive intestinal peptide (VIP) is a molecule shared by the neuroendocrine immune network and is considered to be a potential candidate for treatment of inflammatory and autoimmune diseases. Although some recent studies demonstrate that VIP has a protective role in animal RA models, its variant in different disease grade of OA remains uncertain.Fifty patients with primary knee OA and ten controls with severe trauma were enrolled. Synovial fluid and articular cartilage samples were collected from specimens of total knee arthroplasty (TKA) or knee above amputation. VIP levels in these samples were assessed by ELISA and immunohistochemistry. Kellgren-Lawrence criteria and Mankin score were taken to determine the disease severity.Compared to the controls, OA patients have lower VIP concentration in synovial fluid (659.70±112.79, 95%CI 579.01-740.38 vs 470.83±156.40, 95%CI 426.38-515.28 pg/mL, P0.001) and articular cartilage (0.26±0.02, 95%CI 0.24-0.28 vs 0.20±0.04, 95%CI 0.18-0.21, P0.001). Subsequent analysis show that the VIP expression in synovial fluid is markedly correlated with its OD in articular cartilage (Pearson's r=0.580, P0.001). Furthermore, the synovial fluid and articular cartilage levels of VIP both demonstrated to be negatively correlated with severity of disease (Spearman's ρ=0.838, P0.001; Spearman's ρ=0.814, P0.001).VIP in synovial fluid and articular cartilage is negatively associated with progressive joint damage in OA and is a potential indictor of disease severity.

To examine the relationship between serum calcium (Ca) concentration and radiographic knee osteoarthritis (OA). This study covered a total of 2855 subjects. The serum Ca concentration was detected by the Arsenazo III method. The radiographic OA of the knee was defined as changes equivalent to Kellgren–Lawrence grade 2 on 1 side at least. The serum Ca concentration was categorized into 4 quartiles, which are ≤2.27, 2.28–2.34, 2.35–2.41, and ≥2.42 mmol/L, respectively. The relationship between serum Ca and radiographic knee OA was examined using the multivariable logistic analysis after adjusting a series of potential confounding factors. For each quartile of the relationship between serum Ca concentration and radiographic knee OA, the OR with 95% CI was calculated, and the one with the lowest value was considered to be the reference. An inverse association existed between serum Ca concentration and radiographic OA of the knee in the multivariable model and the model where the factors of age, sex, and BMI were adjusted. The multivariable-adjusted OR (95% CI) for radiographic knee OA in the second, third, and fourth quartiles of serum Ca concentration were 1.05 (95% CI: 0.83–1.31), 1.01 (95% CI: 0.80–1.27), and 0.79 (95% CI: 0.62–1.00), respectively, in comparison with the reference (first) quartile. A trend approaching to statistical significant (P = 0.06) was observed. Meanwhile, the relative odds of radiographic OA of the knee were decreased by 0.79 times in the fourth quartile in comparison with the reference. There is likely to be an inverse association between serum Ca concentration and radiographic OA of the knee.

Osteopontin (OPN) is associated with the severity and progression of osteoarthritis (OA); however, the mechanism of OPN in the pathogenesis of OA is unknown. In this study, we found that OA patients had higher abundance of OPN and matrix metalloproteinase 13 (MMP13). In chondrocytes, we showed that OPN promoted the production of MMP13 and activation of NF-κB pathway by increasing the abundance of p65 and phosphorylated p65 and translocation of p65 protein from cytoplasm to nucleus. Notably, inhibition of NF-κB pathway by inhibitor suppressed the production of MMP13 induced by OPN treatment. In conclusion, OPN induces production of MMP13 through activation of NF-κB pathway.

Background: The clinical relationship between medial meniscus tear and anterior cruciate ligament (ACL) rupture has been well documented. However, the mechanism of this clinical phenomenon is not exactly explained. Our aim is to investigate the biomechanical impact of partial and complete ACL rupture on different parts of medial meniscus. Materials and Methods: Twelve fresh human cadaveric knee specimens were divided into four groups: ACL intact (ACL-I), anteromedial bundle transection (AMB-T), posterolateral bundle transection (PLB-T), and ACL complete transection (ACL-T) group. Strain on the anterior horn, body part, and posterior horn of medial meniscus were measured under 200 N axial compressive tibial load at 0°, 30°, 60°, and 90° of knee flexion, respectively. Results: Compared with the control group (ACL-I), the ACL-T group had a higher strain on whole medial meniscus at 0°, 60°, and 90° of flexion. But at 30°, it had a higher strain on posterior horn of meniscus only. As to PLB-T group, strain on whole meniscus increased at full extension, while strain increased on posterior horn at 30° and on body of meniscus at 60°. However, AMB-T only brought about higher strain at 60° of flexion on body and posterior horn of meniscus. Conclusions: Similar to complete rupture, partial rupture of ACL can also trigger strain concentration on medial meniscus, especially posterior horn, which may be a more critical reason for meniscus injury associated with chronic ACL deficiency.

The aim of this meta-analysis was to examine the effect of the intercondylar notch dimensions, intercondylar notch width index (NWI) and intercondylar notch width (NW), separately in anterior cruciate ligament (ACL) injury. The PubMed and Wanfang database were searched through until 1 November 2011 to identify studies that met pre-stated inclusion criteria. Reference lists of retrieved articles were also reviewed. Two authors independently extracted information on the designs of the studies, the characteristics of the study participants, exposure and outcome assessments and control for potential confounding factors. Either a fixed- or a random-effects model was used to calculate the overall weighted mean difference (WMD). Sixteen studies (n = 4,291) were included (1,222 subjects in ACL-injured group and 3,069 subjects in the control group). Statistically significant differences were observed in the NWI (WMD, −0.02; 95 % confidence interval, −0.04 to −0.01), and in the NW (WMD, −2.15; 95 % confidence interval, −3.09 to −1.21) among the ACL-injured group when compared to the control group. The meta-analysis findings concluded that narrow intercondylar notch dimensions were associated with the risk of ACL injury. A lower NWI or NW stenosis predisposes an individual to ACL injury. Further original studies should include more anatomical risk factors that could be associated with the risk of ACL injury. III.

OBJECTIVE: A meta-analysis to compare the intraoperative and postoperative outcome data for the proximal femoral nail antirotation (PFNA) and dynamic hip screw (DHS) implant systems for the treatment of patients with trochanteric fractures. METHODS: A detailed search of several electronic databases was undertaken to identify randomized controlled trials published before 5 December 2011 that compared PFNA with DHS in patients with trochanteric fractures. RESULTS: A quantitative meta-analysis of 11 studies including 798 patients was performed. PFNA was associated with significant reductions in duration of surgery (weighted mean difference [WMD] −21.38 min; 95% confidence interval [CI] −33.50, −9.26 min), intraoperative blood loss (WMD −176.36 ml; 95% CI −232.20, −120.52 ml), rate of fixation failure (relative risk [RR] 0.27, 95% CI 0.11, 0.62) and rate of postoperative complications (RR 0.46; 95% CI 0.31, 0.70) compared with DHS. CONCLUSION: The use of PFNA for treatment of trochanteric fractures was found to be superior to DHS in terms of the duration of surgery, intraoperative blood loss, and rates of fixation failure and overall complications.

The aim of this study was to investigate the effect of hyaluronic acid (HA) on the expression of osteopontin (OPN) and CD44 mRNA of fibroblast-like synoviocytes (FLS) in the patients with osteoarthritis (OA) of the knee. FLS were obtained from the knees of 10 patients with OA. Real-time quantitative polymerase chain reaction (Q-PCR) was used to assess the expression of the OPN mRNA and CD44 mRNA. The relative OPN mRNA expression in HA group (6.47 ± 2.30-fold) was significantly higher than in the control group (P = 0.045, P0.05), while in HYL group (0.65 ± 0.21-fold) it was lower than in the control group (P = 0.037, P0.05), and the difference in OPN mRNA expression between HA group and HYL group also showed statistically significant (P = 0.001, P0.05); however, there was no significant difference between each group of the relative CD44 mRNA expression (P0.05). Our study showed that HA can upregulate OPN mRNA expression in OA fibroblast-like synoviocytes, and the high expression of OPN mRNA in OA may be a result of increased HA level of OA synovitis; however, HA cannot affect the CD44 mRNA expression in OA fibroblast-like synoviocytes, and the high expression of CD44 mRNA in OA may be not a result of increased HA level of OA synovitis.

Objective: To investigate the biomechanical impact of rupture of the posterior cruciate ligament (PCL) and its various bundles on the medial femoral condyle. Methods: Twelve fresh human cadaveric knee specimens were divided into four groups: PCL intact, anterolateral band (ALB) rupture, posteromedial band (PMB) rupture and PCL complete rupture groups according to the purpose and order of testing. Strain in the middle of the medial femoral condyle was measured under different loads (200–800 N) at 0°, 30°, 60°, and 90° of knee flexion. Results: At 0° of knee flexion, compared with the PCL intact and ALB rupture groups, strain on the medial femoral condyle increased in the PMB rupture and PCL complete rupture groups under all loading conditions. There was no statistical difference between the PMB rupture and PCL complete rupture groups. At 30°, 60° and 90° of knee flexion, compared with the PCL intact group, increase in strain on the medial femoral condyle was noted in the ALB rupture group under higher loading conditions (600 N and 800 N) and PCL complete rupture group under all loading conditions. The PCL complete rupture group had higher strain on the medial femoral condyle than did the ALB rupture group under most loading conditions. Conclusion: At 0° of knee flexion, PMB rupture or PCL complete rupture can cause increase in strain on the medial femoral condyle. However, at 30°, 60° and 90° of knee flexion, ALB rupture or PCL complete rupture can cause increase in strain on the medial femoral condyle.

This study aimed to investigate the effectiveness and safety of glucosamine, chondroitin, the two in combination, or celecoxib in the treatment of knee osteoarthritis (OA). PubMed, Embase and Cochrane Library were searched through from inception to February 2015. A total of 54 studies covering 16427 patients were included. Glucosamine plus chondroitin, glucosamine alone and celecoxib were all more effective than placebo in pain relief and function improvement. Specifically, celecoxib is most likely to be the best treatment option, followed by the combination group. All treatment options showed clinically significant improvement from baseline pain, but only glucosamine plus chondroitin showed clinically significant improvement from baseline function. In terms of the structure-modifying effect, both glucosamine alone and chondroitin alone achieved a statistically significant reduction in joint space narrowing. Although no significant difference was observed among the five options with respect to the three major adverse effects (withdrawal due to adverse events, serious adverse events and the number of patients with adverse events), the additional classical meta-analysis showed that celecoxib exhibited a higher rate of gastrointestinal adverse effect comparing with the placebo group. The present study provided evidence for the symptomatic efficacy of glucosamine plus chondroitin in the treatment of knee OA.

To examine the cross-sectional associations of the serum uric acid level and hyperuricemia (HU) with the radiographic features of osteoarthritis (OA), including osteophytes (OST) and joint space narrowing (JSN), a total of 4685 subjects were included in this study. Blood samples were drawn from all subjects. Serum uric acid and some other indexes were detected. OST and JSN were assessed for each subject according to the Osteoarthritis Research Society International (OARSI) atlas. A multivariable logistic analysis model was applied to test the target associations after adjusting a number of potential confounding factors. The prevalence of OST was increased in the highest tertile of uric acid compared to the lowest in female subjects (OR 1.46, 95 % CI 1.07-1.99, P for trend = 0.02). Meanwhile, a positive association between OST and HU was observed in female subjects (OR 1.43, 95 % CI 1.01-2.03, P = 0.05). However, serum uric acid and HU were not significantly associated with JSN in male subjects. The findings of this study indicated that the serum uric acid concentration and prevalence of HU are positively associated with OST of the knee in the female population. Level of evidence Cross-sectional study, Level III.

Objective To examine the associations between dietary zinc intake and hyperuricaemia. Design Cross-sectional study. Setting This study was conducted in a health examination centre of China. Participants A total of 5168 middle-aged and older participants (aged 40 years or above) (2697 men and 2471 women) were included. Outcome measures Dietary zinc intake was assessed using a validated semiquantitative food frequency questionnaire. Hyperuricaemia was defined as uric acid ≥416 µmol/L for males and ≥360 µmol/L for females. Results For males, the prevalence of hyperuricaemia was 22.9%. After adjusting for age, body mass index (BMI) and energy intake, the ORs were 0.68 (95% CI 0.45 to 0.92) in the second quintile, 0.63 (95% CI 0.45 to 0.89) in the third quintile, 0.68 (95% CI 0.46 to 1.00) in the fourth quintile and 0.55 (95% CI 0.35 to 0.87) in the fifth quintile comparing the lowest quintile of Zn intake, respectively (p for trend=0.03). In the multivariable adjusted model, the relative odds of hyperuricaemia were significantly decreased by 0.71 times in the second quintile of zinc intake (OR 0.71, 95% CI 0.52 to 0.98), 0.64 times in the third quintile (OR 0.65, 95% CI 0.44 to 0.94) and 0.55 times in the fifth quintile (OR 0.56, 95% CI 0.32 to 0.97) compared with those in the lowest quintile, and p for trend was 0.064. For females, the prevalence of hyperuricaemia was 10.0%, and unadjusted, minimally adjusted as well as multivariable adjusted ORs all suggested no significant association between dietary zinc intake and hyperuricaemia. Conclusions The findings of this cross-sectional study indicated that dietary zinc intake was inversely associated with hyperuricaemia in middle-aged and older males, but not in females. The association was significant after considering the influence of age, BMI and energy intake, and after that, minimum adjustment remained independent of further confounding factors such as vitamin C intake, alcohol drinking status and nutrient supplementation.

The aim of the study was to examine the cross-sectional association between high-sensitivity C-reactive protein (hsCRP) and hyperuricemia (HU). The hsCRP was measured by latex turbidity method. Uric acid was detected on Beckman Coulter AU 5800. HU was defined as uric acid ≥416 μmol/L for the male population and ≥360 μmol/L for the female population. A multivariable logistic analysis model was applied to test the association after adjusting for a number of potential confounding factors. A total of 1935 subjects were included in this study. According to the multivariable regression model, the relative odds of the prevalence of HU were increased by 0.56 times in the third quintile (OR 1.56, 95 % CI 1.03-2.38, P = 0.04), 0.55 times in the fourth quintile (OR 1.55, 95 % CI 1.01-2.36, P = 0.04) and 0.96 times in the fifth quintile (OR 1.96, 95 % CI 1.29-2.98, P

Aim The purposes of this study were to investigate senescence-associated beta-galactosidase (SA-beta-Gal) levels in articular cartilage of knee osteoarthritis (OA) and the relationship with severity of the disease. Methods All the 50 cartilage tissues, including normal (controls) and OA cartilage were ascribed to four groups of normal, mild lesions, moderate lesions and severe lesions on the basis of the modified Mankin score. Immunohistochemistry was used to assess the SA-beta-Gal expression in articular cartilage. Results No SA-beta-Gal staining was observed in the normal articular cartilage samples. SA-beta-Gal staining was found in a subset of the chondrocytes close to the lesion site of mild, moderate and severe damaged knee OA cartilage. The percentage of SA-beta-Gal-positive chondrocytes in articular cartilage was 0% in controls, 13.00 ± 5.77% in mild lesions, 31.65 ± 6.91% in moderate lesions and 51.95 ± 6.21% in severe lesions. SA-beta-Gal expression in mild lesions, moderate lesions and severe lesions was higher compared with that of controls (P

This network meta-analysis aimed to investigate the effectiveness and safety of 100 mg BID and 200 mg QD oral celecoxib in the treatment of OA of the knee or hip. PubMed, Embase and Cochrane Library were searched through from inception to August 2014. Bayesian network meta-analysis was used to combine direct and indirect evidences on treatment effectiveness and safety. A total of 24 RCTs covering 11696 patients were included. For the comparison in between the two dosage regimens, 100 mg BID oral celecoxib exhibited a greater probability to be the preferred one either in terms of pain intensity or function at the last follow-up time point. For total gastrointestinal (GI) adverse effects (AEs), both of the two dosage regimens demonstrated a higher incidence compared to the placebo group. Further analyses of GI AEs revealed that only 200 mg QD was associated with a significantly higher risk of abdominal pain when compared with placebo. Furthermore, 100 mg BID showed a significantly lower incidence of skin AEs when compared with 200 mg QD and placebo. Maybe 100 mg BID should be considered as the preferred dosage regimen in the treatment of knee or hip OA.

Degradation of the articular cartilage is at the centre of the pathogenesis of osteoarthritis (OA), for which age is the major risk factor. Maintaining the chondrocytes in a healthy condition appears to be an important factor for preservation of the entire cartilage and preventing its degeneration. Autophagy, which is an essential cellular homeostatic mechanism for the removal of dysfunctional cellular organelles and macromolecules, is increased by catabolic and nutritional stresses. Autophagy is increased in OA chondrocytes and cartilage, particularly during the initial degenerative phase, to regulate changes in OA-like gene expression through modulation of apoptosis and reactive oxygen species (ROS). In this way, autophagy acts as an adaptive response to protect chondrocytes from various environmental changes, while with gradual cartilage degradation, decreased autophagy is linked with cell death. Rapamycin, which is a specific inhibitor of the mTOR signaling pathway, enhances expression of autophagy regulators and prevents chondrocyte death. In the future, pharmacological activation of autophagy may be an effective therapeutic approach for OA.

Wnt inhibitory factor (WIF)-1 is a potent extracellular Wnt antagonist which may be used as a potential molecular therapy for the treatment of inflammatory and autoimmune diseases. Although previous studies have demonstrated that WIF-1 has a protective role in experimental studies of arthritis, its role in the various disease grades of osteoarthritis (OA) remains unclear. A total of 40 patients with various stages of primary OA of the knee and 10 control subjects were enrolled in the present study. Articular cartilage specimens were harvested from subjects following total knee arthroplasty or knee above amputation. Disease severity was determined according to Modified Mankin score and cartilage tissues were ascribed to four groups: Normal, mild, moderate and severe lesions. WIF-1 expression levels in articular cartilage were measured using immunohistochemical techniques. WIF-1 expression levels were detected in all cartilage tissues. As compared with the controls, patients with OA exhibited significantly decreased WIF-1 expression levels in the articular cartilage (0.19±0.05 vs. 0.26±0.04; P

We read with great interest the article by Jiang and colleagues in a recent issue of Arthritis Research & Therapy related to osteopontin (OPN) gene polymorphisms influencing the risk of knee osteoarthritis (OA) and the OPN levels in synovial fluid in a Chinese population [1]. The authors showed that the thrombin-cleaved osteopontin (OPN-N) levels in synovial fluid were positively correlated to the radiographic severity of OA, which was consistent with our result [2]. In addition, the group indicated that OPN-N levels (but not the full-length OPN levels) in synovial fluid were significantly lower in certain OPN gene polymorphisms (–443TT and –66GG). We believe this result was very intriguing to lots of readers. However, the discussion of this specific part was unclear and deserves more attention. For the –443 locus, the authors suggested that –443 T had a lower promoter activity that could regulate the OPN gene transcript activity, thus influencing OPN expression. Similarly, for the –66 locus, overexpression of specificity protein 1 induced higher promoter activation on a plasmid carrying the T allele compared with the equivalent plasmid carrying the G allele that was used to explain their findings. In other words, alleles at polymorphic sites in the OPN gene influence the OPN level by influencing the level of promoter activity and characterizing their ability to bind transcription factors that had been proposed by the authors. Perhaps most puzzling of all, these explanations actually conflicted with their findings – certain OPN gene polymorphisms of the two loci (–66, –443) were not associated with full-length OPN, but with OPN-N. Almost at the end of the discussion, the authors postulate that the influence of OPN polymorphisms on risk and severity of OA is very probably due to its effect on the synthesis of the active OPN protein. Combined with the result of the study, we speculate that the authors mean that certain OPN polymorphisms could lead to active OPN protein that can easily be cut by thrombin. However, the loci (–66, –443) are all in the human OPN promoter, but not the coding sequence. Theoretically, a promoter is a region of DNA that initiates transcription of a particular gene that could influence the expression of this gene but may not have an effect on the properties of the corresponding protein. So what are the possible reasons that could explain the high OPN-N level in OA patients? Liu and coworkers suggested that significant higher expression of thrombin was observed in OA synovial fibroblasts than in normal synovial fibroblasts [3]. Ohba and colleagues found high levels of thrombin activity in rheumatoid arthritis [4]. Myles and Leung indicated that OPN cleavage by thrombin was dependent on both anion-binding exosites in thrombin that determined the rates and specificity of thrombin proteolysis [5]. Alongside these potential reasons (higher expression or activity of thrombin), Jones and colleagues found that antithrombin activity is selectively depressed in rheumatoid arthritis synovial fibroblasts [6]. Above all, we respect the great contribution of the authors and have no doubt that the results of the data are accurate. We are just curious about the association between certain OPN gene polymorphisms and OPN-N (not full-length OPN). We would be very grateful if the authors could discuss this association more clearly. The association between certain OPN gene polymorphisms and OPN-N also deserves exploration in further studies.

The joint disease osteoarthritis (OA) is the most common form of arthritis, which mainly affects the older people. OA is becoming one of the major non-fatal health burdens of the world. The etiology of OA is mostly unclear, and it cannot be cured totally. Osteopontin (OPN) is a multifunctional phosphoprotein, of which overexpression and high level of presence in synovial fluid and articular cartilage were found to be associated with OA progression. Usually, in OA progression, OPN plays important role as an intrinsic regulator. Recent studies have taken attempt to use this protein as a diagnostic marker of OA and use OPN as a target for the drug development against OA. This review summarizes the role of OPN in OA, with focusing on the mechanism of action, and also discussing the diagnostic and therapeutic aspects of OA related to OPN.

Objectives A meta-analysis was conducted to examine the effect of mud therapy on pain relief in patients with knee osteoarthritis (OA). Methods A detailed search of PubMed®/MEDLINE® was undertaken to identify randomized controlled trials and prospective comparative studies published before 9 March 2013 that compared mud therapy with control group treatments in patients with knee OA. Results A quantitative meta-analysis of seven studies (410 patients) was performed. There was a significant difference between the groups in the visual analogue scale pain score (standardized mean difference [SMD] −0.73) and Western Ontario and McMaster Universities Osteoarthritis Index pain score (SMD −0.30), with differences in favour of mud therapy. Conclusions Mud therapy is a favourable option for pain relief in patients with knee OA. Additional high-quality randomized controlled trials need to be conducted to explore this issue further and to confirm this conclusion.

The severity of avascular necrosis (AVN) after closed reduction of developmental dysplasia of the hip determines the final clinical outcomes. Our study aimed to correlate the possible predictors with the severity of AVN. After follow-up of the patients on skeletal maturity, 37 patients (39 hips) were included. Age at reduction is important to predict the severity of AVN. Older patients are at a greater risk of suffering from more severe AVN. Other values such as the degree of initial dislocation or the impact of the femoral head ossific nucleus show no precognition to the severity of AVN.

We read with deep interest the article by Kluzek et al ,1 which examined whether joint pain or radiographic osteoarthritis (ROA) of the knee and hand is associated with the all-cause and disease-specific mortality in middle-aged women. The outcome of this prospective community-based Chingford Cohort Study indicated a significantly increased risk of all-cause and cardiovascular disease-specific mortality in women experiencing knee pain with or without ROA, but not in women with ROA alone. It suggests that knee pain, rather than structural changes of osteoarthritis (OA), can be considered as an independent predictor of mortality in middle-aged women. We sincerely appreciate the work performed and the valuable findings obtained by the authors; nevertheless, some issues are worth of further exploration. First, knee pain was selected as an important evaluative parameter to predict mortality in middle-aged women in this study, but there were several factors that can cause knee pain. A substantial part of knee pain might be related to the knee joint itself and another source of knee pain might result from other musculoskeletal diseases. The most common cause of knee pain is an injury, which can …

To investigate CD44 levels in articular cartilage of knee osteoarthritis (OA) and the relationship between CD44 and severity of the disease. All 50 cartilage tissues included normal and OA cartilage, and were ascribed to the following four groups on the basis of modified Mankin score: normal, mild lesions, moderate lesions and severe lesions. CD44 levels in articular cartilage were assessed by immunohistochemical methods. CD44 levels were detected in all four groups. The difference in average gray value of CD44 expression showed statistical significance when compared between each group (P

The purpose of this meta-analysis was (1) to examine the effect of the tibial plateau slopes (medial and lateral) on anterior cruciate ligament (ACL) injury and (2) to investigate gender differences between ACL-injured subjects and gender-matched controls. The PubMed database was searched through to 1 November 2011 to identify studies that met pre-stated inclusion criteria. Reference lists of retrieved articles were also reviewed. Two authors independently extracted information on the designs of the studies, the characteristics of the study participants, exposure and outcome assessments, and control for potential confounding factors. A meta-analysis was conducted, and either a fixed- or a random-effects model was used to calculate the overall weighted mean difference (WMD). Twelve studies (n = 1,871: 923 patients in the ACL-injured group and 938 patients in the control group) were included. The medial tibial plateau slope in the ACL group ranged from 1.8° ± 3.7° to 12.1° ± 3.3° while it ranged from 2.9° ± 2.8° to 9.5° ± 3° among the controls. The lateral tibial plateau slope in the ACL ranged from 1.8° ± 3.2° to 11.5° ± 3.5° and 0.3° ± 3.6° to 9° ± 4° in the control group. Statistically significant increased angles were observed in ACL-injured group compared to control group for medial tibial plateau slope (WMD, 1.1°; 95 % confidence interval, 0.5°–1.7°) and lateral tibial plateau slope (WMD, 1.8°; 95 % confidence interval, 1.3°–2.3°). Sensitivity analysis and subgroup analysis proved this to be a reliable result. The current meta-analysis suggests that both, increased medial and lateral tibial plateau slopes, are associated with increased susceptibility to ACL injury regardless of gender. In addition, this study indicates a stronger evidence for lateral tibial plateau slope to be associated with ACL injury compared with medial tibial plateau slope due to the larger increased angle value and on the basis of consistency among the included studies. III.

The purpose of this study is to observe the differences of osteopontin (OPN) phosphorylation in osteoarthritis (OA) cartilage and normal cartilage, and evaluate the possible correlations between the OPN phosphorylation and MMP-13 expression. Degenerative cartilage (n = 29) and normal cartilage (n = 10) were identified by hematoxylin-eosin, safranin-O staining and modified Mankin score. The phosphorylation level of OPN in OA cartilage and normal cartilage was detected by immunoprecipitation. Chondrocytes were treated with phospho-OPN, OPN or buffer. Quantitative reverse transcription polymerase chain reaction (qPCR) and ELISA were used to assess the expression of MMP-13 in different treatments. The OD values of phosphorylation of OPN in normal cartilage and OA cartilage were 137.89 ± 10.59 and 153.52 ± 8.80, respectively, (P = 0.000). Chondrocytes treated with OPN showed a higher MMP-13 expression at gene and protein level compared with control group. Chondrocytes treated with phospho-OPN showed the highest MMP-13 expression in gene and protein. In conclusion, our results revealed a higher phosphorylation level of OPN in OA cartilage than in normal cartilage. We found OPN leads to elevated expression of MMP-13 (both at gene level and protein level), and phospho-OPN had a more obvious upregulation effect on MMP-13 expression than nonphospho-OPN. Further studies are needed to reveal the mechanism of OPN phosphorylation on cartilage degeneration.

Background Many studies have identified smoking as a risk factor for osteoporosis, but it is unclear whether passive smoking has an effect on bone mineral density and bone turnover and if such an effect could cause osteoporosis.The purpose of the study was to investigate the effect of passive smoking on bone mineral density (BMD) and bone turnover and the relationship between BMD and bone turnover in female rat. Methods Forty-eight female Wistar rats were randomized into six groups: 2-month, 3-month,4-month smoke-exposed rats and their controls. A rat model of passive cigarette smoking was prepared by breeding female rats in a cigarette-smoking box for 2, 3 or 4 months. Serums were analyzed for levels of osteocalcin, bone-specific alkaline phosphatase (b-ALP) and Tartrate-resistant acid phosphatase 5b (TRACP 5b). BMD was assessed at lumbar vertebrae and femur by dual energy X-ray absorptiometry in passive smoking rats and in control rats. Results BMD of lumbar spine and femur was lower in 4-month smoke-exposed female rats than that in controls. However, there was no significant difference in serum osteocalcin levels between smoke-exposed rats and controls. Significantly lower b-ALP and higher TRACP 5b were found in the 3-month or 4-month smoke-exposed rats compared to controls. Subsequent analysis showed that b-ALP positively correlated with BMD of the lumbar vertebrae(r = 0.764, P = 0.027) and femur(r = 0.899, P = 0.002) in 4-month smoke-exposed female rats. Furthermore, TRACP 5b levels negatively correlated with BMD of lumbar vertebrae (r = -0.871, P = 0.005) and femur (r = -0.715, P = 0.046) in 4-month smoke-exposed female rats. Conclusion Our data suggest that smoke exposure can inhibit bone formation and increase bone resorption. The hazardous effects of passive smoking on bone status are associated with increased bone turnover in female rat.

The goal of this study was to evaluate the array of causative organisms for septic arthritis in children and their antibiotic resistance patterns over a 20-year period at a single medical center. The medical records of children younger than 16 years with septic arthritis admitted to a hospital in China from 1989 to 2008 were retrospectively reviewed. A total of 158 cases of septic arthritis were studied, 70 from 1989 to 1998 and 88 from 1999 to 2008. Between the first and second decades, occurrence of serious illnesses decreased significantly from 44.3% to 28.4% ( P Staphylococcus aureus (MRSA) increasing significantly. Staphylococci remained the major causative organisms for joint infection. The percentage of Staphylococcus aureus resistance to various antibiotics increased: 85% to 100% for penicillin, 58.8% to 75% for erythromycin, 0% to 31.3% for cefazolin, and 15% to 29.4% for multi-resistance. In the second decade, 4 MRSA stains were multi-resistant. However, gentamincin resistance remained at the same level. Antibiotic resistance of coagulase-negative staphylococci and gram-negative bacilli changed little. The incidences of osteomyelitis and joint dislocation decreased significantly, from 15.7% to 6% and 28.6% to 14.8%, respectively ( P

We read with deep interest the article by Callaghan et al 1 related to the efficacy of patellar brace in patients with patellofemoral (PF) osteoarthritis (OA) targeting knee pain and bone marrow lesions (BMLs). To our best knowledge, patellar brace in the management of PF disorders, including PF arthritis, was first introduced in 1981.2 Since then only a few studies have examined the effects of patellar brace on the treatment of PF OA. This high-quality randomised controlled trial suggested that a PF brace reduced BML volume in the targeted compartment of the knee and relieved knee pain. These results were ‘promising’ in a situation where only a few conservative treatments have been consistently shown to affect structural findings. We really appreciate the work done …

Background: The relationship between medial meniscus tear and posterior cruciate ligament (PCL) injury has not been exactly explained. We studied to investigate the biomechanical effect of partial and complete PCL transection on different parts of medial meniscus at different flexion angles under static loading conditions. Materials and Methods: Twelve fresh human cadaveric knee specimens were divided into four groups: PCL intact (PCL-I), anterolateral bundle transection (ALB-T), posteromedial bundle transection (PMB-T) and PCL complete transection (PCL-T) group. Strain on the anterior horn, body part and posterior horn of medial meniscus were measured under different axial compressive tibial loads (200-800 N) at 0°, 30°, 60° and 90° knee flexion in each groups respectively. Results: Compared with the PCL-I group, the PCL-T group had a higher strain on whole medial meniscus at 30°, 60° and 90° flexion in all loading conditions and at 0° flexion with 400, 600 and 800 N loads. In ALB-T group, strain on whole meniscus increased at 30°, 60° and 90° flexion under all loading conditions and at 0° flexion with 800 N only. PMB-T exihibited higher strain at 0° flexion with 400 N, 600 N and 800 N, while at 30° and 60° flexion with 800 N and at 90° flexion under all loading conditions. Conclusions: Partial PCL transection triggers strain concentration on medial meniscus and the effect is more pronounced with higher loading conditions at higher flexion angles.

SummaryObjectiveTo investigate osteopontin (OPN) levels in both synovial fluid and articular cartilage of patients with primary knee osteoarthritis (OA) and their relationship with severity of the disease.MethodFifty patients aged 48–81 years with knee OA and 10 healthy controls were enrolled in this study. Anteroposterior knee radiographs or/and Mankin score were taken to determine the disease severity of the affected knee. The radiographic grading of OA in the knee was performed by using the Kellgren-Lawrence criteria. OPN levels in synovial fluid were measured using enzyme-linked immunosorbent assay. OPN levels in articular cartilage were assessed by immunohistochemical methods.ResultsCompared to healthy controls, OA patients had higher OPN concentration in synovial fluid (4519.60±1830.37, 95%CI 3999.42–5039.79 vs 1179.70±303.39, 95%CI 1035.53–1438.74pg/ml, P

Background Epimedii herba is one of the most frequently used herbs in formulas that are prescribed for the treatment of osteoporosis in China and its main constituent is Epimedium pubescen flavonoid (EPF). However, it is unclear whether EPF during chronic exposure to cigarette smoke may have a protective influence on the skeleton. The present study investigated the effect of EPF on bone mineral status and bone turnover in a rat model of human relatively high exposure to cigarette smoke. Methods Fifty male Wistar rats were randomized into five groups: controls, passive smoking groups and passive smoking rats administered EPF at three dosage levels (75, 150 or 300 mg/kg/day) in drinking water for 4 months. A rat model of passive smoking was prepared by breeding male rats in a cigarette-smoking box. Bone mineral content (BMC), bone mineral density (BMD), bone turnover markers, bone histomorphometric parameters and biomechanical properties were examined. Results Smoke exposure decreased BMC and BMD, increased bone turnover (inhibited bone formation and stimulated its resorption), affected bone histomorphometry (increased trabecular separation and osteoclast surface per bone surface; decreased trabecular bone volume, trabecular thickness, trabecular number, cortical thickness, bone formation rate and osteoblast surface per bone surface), and reduced mechanical properties. EPF supplementation during cigarette smoke exposure prevented smoke-induced changes in bone mineral status and bone turnover. Conclusion The results suggest that EPF can prevent the adverse effects of smoke exposure on bone by stimulating bone formation and inhibiting bone turnover and bone resorption.