Aged bone marrow macrophages drive systemic aging and age-related dysfunction via extracellular vesicle-mediated induction of paracrine senescence.

The accumulation and systemic propagation of senescent cells contributes to physiological aging and age-related pathology. However, which cell types are most susceptible to the aged milieu and could be responsible for the propagation of senescence has remained unclear. Here we found that physiologically aged bone marrow monocytes/macrophages (BMMs) propagate senescence to multiple tissues, through extracellular vesicles (EVs), and drive age-associated dysfunction in mice. We identified peroxisome proliferator-activated receptor α (PPARα) as a target of microRNAs within aged BMM-EVs that regulates downstream effects on senescence and age-related dysfunction. Demonstrating therapeutic potential, we report that treatment with the PPARα agonist fenofibrate effectively restores tissue homeostasis in aged mice. Suggesting conservation to humans, in a cohort study of 7,986 participants, we found that fenofibrate use is associated with a reduced risk of age-related chronic disease and higher life expectancy. Together, our findings establish that BMMs can propagate senescence to distant tissues and cause age-related dysfunction, and they provide supportive evidence for fenofibrate to extend healthy lifespan.

Macrophage-derived extracellular vesicles regulate skeletal stem/progenitor Cell lineage fate and bone deterioration in obesity.

Obesity-induced chronic inflammation exacerbates multiple types of tissue/organ deterioration and stem cell dysfunction; however, the effects on skeletal tissue and the underlying mechanisms are still unclear. Here, we show that obesity triggers changes in the microRNA profile of macrophage-secreted extracellular vesicles, leading to a switch in skeletal stem/progenitor cell (SSPC) differentiation between osteoblasts and adipocytes and bone deterioration. Bone marrow macrophage (BMM)-secreted extracellular vesicles (BMM-EVs) from obese mice induced bone deterioration (decreased bone volume, bone microstructural deterioration, and increased adipocyte numbers) when administered to lean mice. Conversely, BMM-EVs from lean mice rejuvenated bone deterioration in obese recipients. We further screened the differentially expressed microRNAs in obese BMM-EVs and found that among the candidates, miR-140 (with the function of promoting adipogenesis) and miR-378a (with the function of enhancing osteogenesis) coordinately determine SSPC fate of osteogenic and adipogenic differentiation by targeting the Pparα-Abca1 axis. BMM miR-140 conditional knockout mice showed resistance to obesity-induced bone deterioration, while miR-140 overexpression in SSPCs led to low bone mass and marrow adiposity in lean mice. BMM miR-378a conditional depletion in mice led to obesity-like bone deterioration. More importantly, we used an SSPC-specific targeting aptamer to precisely deliver miR-378a-3p-overloaded BMM-EVs to SSPCs via an aptamer-engineered extracellular vesicle delivery system, and this approach rescued bone deterioration in obese mice. Thus, our study reveals the critical role of BMMs in mediating obesity-induced bone deterioration by transporting selective extracellular-vesicle microRNAs into SSPCs and controlling SSPC fate.

Age-related secretion of grancalcin by macrophages induces skeletal stem/progenitor cell senescence during fracture healing.

Skeletal stem/progenitor cell (SSPC) senescence is a major cause of decreased bone regenerative potential with aging, but the causes of SSPC senescence remain unclear. In this study, we revealed that macrophages in calluses secrete prosenescent factors, including grancalcin (GCA), during aging, which triggers SSPC senescence and impairs fracture healing. Local injection of human rGCA in young mice induced SSPC senescence and delayed fracture repair. Genetic deletion of Gca in monocytes/macrophages was sufficient to rejuvenate fracture repair in aged mice and alleviate SSPC senescence. Mechanistically, GCA binds to the plexin-B2 receptor and activates Arg2-mediated mitochondrial dysfunction, resulting in cellular senescence. Depletion of Plxnb2 in SSPCs impaired fracture healing. Administration of GCA-neutralizing antibody enhanced fracture healing in aged mice. Thus, our study revealed that senescent macrophages within calluses secrete GCA to trigger SSPC secondary senescence, and GCA neutralization represents a promising therapy for nonunion or delayed union in elderly individuals.

Digoxin targets low density lipoprotein receptor-related protein 4 and protects against osteoarthritis.

OBJECTIVES: Dysregulated chondrocyte metabolism is closely associated with the pathogenesis of osteoarthritis (OA). Suppressing chondrocyte catabolism to restore cartilage homeostasis has been extensively explored, whereas far less effort has been invested toward enhancing chondrocyte anabolism. This study aimed to repurpose clinically approved drugs as potential stimulators of chondrocyte anabolism in treating OA. METHODS: Screening of a Food and Drug Administration-approved drug library; Assays for examining the chondroprotective effects of digoxin in vitro; Assays for defining the therapeutic effects of digoxin using a surgically-induced OA model; A propensity-score matched cohort study using The Health Improvement Network to examine the relationship between digoxin use and the risk of joint OA-associated replacement among patients with atrial fibrillation; identification and characterisation of the binding of digoxin to low-density lipoprotein receptor-related protein 4 (LRP4); various assays, including use of CRISPR-Cas9 genome editing to delete LRP4 in human chondrocytes, for examining the dependence on LRP4 of digoxin regulation of chondrocytes. RESULTS: Serial screenings led to the identification of ouabain and digoxin as stimulators of chondrocyte differentiation and anabolism. Ouabain and digoxin protected against OA and relieved OA-associated pain. The cohort study of 56 794 patients revealed that digoxin use was associated with reduced risk of OA-associated joint replacement. LRP4 was isolated as a novel target of digoxin, and deletion of LRP4 abolished digoxin's regulations of chondrocytes. CONCLUSIONS: These findings not only provide new insights into the understanding of digoxin's chondroprotective action and underlying mechanisms, but also present new evidence for repurposing digoxin for OA.

Arthroscopic Treatment of Femoral Avulsion Fracture of the Posterior Cruciate Ligament in Association with Meniscus Tear.

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.

Association Between Magnetic Resonance Imaging-Measured Intercondylar Notch Dimensions and Anterior Cruciate Ligament Injury: A Meta-analysis.

PURPOSE: To explore the association between the magnetic resonance imaging (MRI)-measured intercondylar notch dimensions, including the intercondylar notch width (NW) and intercondylar notch width index (NWI), and the risk of anterior cruciate ligament (ACL) injury by performing a meta-analysis of studies that relied on the multiplanar imaging and soft-tissue visualization strengths of MRI. METHODS: The MEDLINE, Embase, and SportDiscus databases were searched from inception to March 2017. Observational studies reporting on the associations of the NWI and NW with ACL injury were retrieved. A random-effects model was used to calculate the overall weighted mean difference (WMD) between the ACL injury group and control group. RESULTS: A total of 20 studies were included in this meta-analysis. The combined data showed that subjects with ACL injury, as compared with the control group, had a significantly decreased NW (pooled WMD, -1.53 [95% confidence interval, -1.81 to -1.25]; P < .00001) and NWI (pooled WMD, -0.02 [95% confidence interval, -0.03 to -0.01]; P < .00001). Similar findings were observed in subgroup analyses in terms of different injury mechanisms. No significant difference in NWI was found in the axial view. A significantly decreased NW and NWI were found in other plane views. The sensitivity analyses after the exclusion of studies enrolling only athletes or skeletally immature subjects reached similar outcomes. The Begg rank correlation test showed no publication bias. CONCLUSIONS: With the accumulation of evidence, this meta-analysis concluded that the NW and/or NWI measured by MRI was significantly lower in ACL-injured patients than in control subjects. For persons with a narrow intercondylar notch, preventive measures can be prepared for the prevention of ACL injuries. LEVEL OF EVIDENCE: Level III, meta-analysis of Level II and III studies.

Association between metabolic syndrome and knee osteoarthritis: a cross-sectional study.

BACKGROUND: Osteoarthritis (OA) is the most prevalent chronic joint disease in China. The aim of this study was to examine the association between metabolic syndrome (MetS) and knee OA in a population-based Chinese study. METHODS: Data included in this analysis is from a cross-sectional study, i.e., the Xiangya Hospital Health Management Center Study. MetS was diagnosed according to the criteria defined by the Chinese Diabetes Society. Radiographic knee OA was defined as changes equivalent to Kellgren-Lawrence (K-L) grade 2 or above at least one side. Associations between MetS and its components with OA were evaluated by conducting multivariable adjusted logistic regression. RESULTS: A total of 5764 participants were included in the present study. The unadjusted OR (1.27, 95%CI: 1.10-1.47, P = 0.001), age-sex adjusted OR (1.17, 95%CI: 1.01-1.36, P = 0.041) and multivariable adjusted OR (1.17, 95%CI: 1.01-1.36, P = 0.043) all suggested a positive association between MetS and knee OA. Besides, its components (e.g., overweight, hypertension and dyslipidemia) were also associated with the prevalence of radiographic knee OA respectively, after adjusting for some confounding factors. In addition, with the accumulation of MetS components, the prevalence of knee OA increased. Furthermore, MetS as a whole was associated with the prevalence of knee osteophyte (OSP) (OR = 1.72, 95%CI: 1.42-2.09, P < 0.001), but not joint space narrowing (JSN) (OR = 1.06, 95%CI: 0.91-1.23, P = 0.449). CONCLUSIONS: The findings of the present study indicated that there was a positive association between the prevalence of MetS and knee OA. However, MetS as a whole was associated with the higher prevalence of knee OSP, but not JSN, which should shed light on our understanding the association between MetS and OA.

Dose-response relationship between lower serum magnesium level and higher prevalence of knee chondrocalcinosis.

BACKGROUND: The aim was to assess serum magnesium levels in relation to prevalence of knee chondrocalcinosis in two population-based Chinese studies. METHODS: Data included in this analysis consisted of two population-based cross-sectional studies, i.e., the Xiangya Hospital Health Management Center Study and the Xiangya Osteoarthritis (XO) Study I. A bilateral knee anteroposterior radiograph was obtained from each subject. Radiographic knee chondrocalcinosis was present if there was definite linear cartilage calcification. Serum magnesium concentration was measured using the chemiluminescence method. We examined the relation of serum magnesium levels to prevalence of knee chondrocalcinosis using generalized estimating equations. RESULTS: The prevalence of knee chondrocalcinosis was 1.4% in the Xiangya Hospital Health Management Center Study (n = 12,631). Compared with the lowest tertile, the age, sex and body mass index (BMI)-adjusted odds ratios (ORs) of chondrocalcinosis were 0.59 (95% CI 0.40-0.87) and 0.49 (95% CI 0.33-0.72) in the second and the third tertiles of serum magnesium, respectively (P for trend <0.001). The prevalence of knee chondrocalcinosis in the XO Study I (n = 1316) was 4.1%. The age, sex and BMI-adjusted ORs of chondrocalcinosis were 0.67 (95% CI 0.34-1.30) in the second and 0.45 (95% CI 0.21-0.94) in the third tertile of serum magnesium when compared with the lowest tertile (P for trend = 0.030). Similar results were observed in men and women in both studies. Adjusting for additional potential confounders did not change the results materially. CONCLUSIONS: Subjects with lower levels of serum magnesium, even within the normal range, had higher prevalence of knee chondrocalcinosis in a dose-response relationship manner, suggesting that magnesium may have a preventive or therapeutic potential for knee chondrocalcinosis.

Overactivated autophagy contributes to steroid-induced avascular necrosis of the femoral head.

Steroid-induced avascular necrosis of the femoral head (SANFH) is a mainly bilateral complication of steroid therapy that involves extensive necrosis, and frequently occurs in young and middle-aged individuals, with a high disability rate. Autophagy is an intracellular lysosomal degradation process occurring in numerous diseases. However, the effect of dexamethasone (DXM)-induced autophagy on osteoblasts is unclear. The aim of the present study was to investigate the effects of autophagy on SANFH. In the present study, femoral head of SANFH patients was collected, and the autophagy in the samples was evaluated. In addition, cell proliferation, membrane integrity and differentiation of osteoblasts were also detected to confirm the effect of DXM on a mouse osteoblasts cell MC3T3-E1 in vitro. Beclin 1 and microtubule-associated protein 1 light chain 3 were used as the markers of autophagy, while the autophagy inhibitor 3-methyladenine (3-MA) was used to investigate the role of autophagy in DXM-challenged osteoblasts. Immunohistochemistry results demonstrated that Beclin1 was markedly increased in the femoral head of SANFH patients. Furthermore, the treatment of osteoblasts with DXM decreased cell viability, increased lactate dehydrogenase activity in the cell culture supernatant, and reduced the alkaline phosphatase activity and bone morphogenetic protein-2 expression in osteoblasts in vitro. By contrast, 3-MA treatment attenuated the cell injury induced by DXM. The present study indicates that overactivated autophagy may be an important factor contributing to SANFH, and autophagy may be a potential target for the prevention of SANFH.

T Cells in Osteoarthritis: Alterations and Beyond.

Although osteoarthritis (OA) has been traditionally regarded as a non-inflammatory disease, reports increasingly suggest that it is inflammatory, at least in certain patients. OA patients often exhibit inflammatory infiltration of synovial membranes by macrophages, T cells, mast cells, B cells, plasma cells, natural killer cells, dendritic cells, granulocytes, etc. Although previous reviews have summarized the knowledge of inflammation in the pathogenesis of OA, as far as we know, no report review our current understanding about T cells, especially, each T cell subtype, in the biology of OA. This review highlights the current understanding of the role of T cells in the pathogenesis of OA, with attention to Th1 cells, Th2 cells, Th9 cells, Th17 cells, Th22 cells, regulatory T cells, follicular helper T cells, cytotoxic T cells, T memory cells, and even unconventional T cells (e.g., γδ T cells and cluster of differentiation 1 restricted T cells). The findings highlight the importance of T cells to the development and progression of OA and suggest new therapeutic approaches for OA patients based on the manipulation of T-cell responses.

Association Between Tibial Plateau Slopes and Anterior Cruciate Ligament Injury: A Meta-analysis.

PURPOSE: To investigate the associations of medial tibial plateau slope (MTPS), lateral tibial plateau slope (LTPS), and coronal tibial plateau slope (CTPS) with anterior cruciate ligament (ACL) injury both in the general population and in different gender subgroups. METHODS: PubMed, Ovid, Embase, and Scopus databases were searched through from inception to August 31, 2016. Observational studies reporting associations of MTPS/LTPS/CTPS with ACL injury were retrieved for analysis. Either a fixed- or random-effects model was used to calculate the overall standardized mean difference (SMD). Reviews, meeting abstracts, cadaver or animal studies, and other studies without disclosing full text were excluded in this study. RESULTS: A total of 29 studies were included. Subjects with ACL injury exhibited a significant increase in MTPS (SMD: 0.34 [95% confidence interval (CI): 0.18, 0.49]; P < .0001) and LTPS (SMD: 0.49 [95% CI: 0.30, 0.68]; P < .00001), but not in the CTPS (SMD: 0.09 [95% CI: -0.10, 0.27]; P = .36), compared with controls. Meanwhile, significant differences in MTPS and LTPS were observed in the male subgroup (SMD: 0.41 [95% CI: 0.20, 0.62]; P = .0001 and SMD: 0.55 [95% CI: 0.26, 0.85]; P = .0002, respectively) but not in the female (SMD: 0.31 [95% CI: -0.02, 0.64]; P = .06 and SMD: 0.26 [95% CI: -0.04, 0.56]; P = .09, respectively). CONCLUSIONS: The present meta-analysis showed that the increases in MTPS and LTPS were overall risk factors of ACL injury. However, these slopes would only be considered as "at risk" for males, but not for females. In addition, it was also proved that CTPS was not a risk factor of ACL injury. LEVEL OF EVIDENCE: Level III, meta-analysis of Level II and III studies.

Is tea consumption associated with the serum uric acid level, hyperuricemia or the risk of gout? A systematic review and meta-analysis.

BACKGROUND: The aim of this study was to examine the associations of tea consumption with the serum uric acid (SUA) level, hyperuricemia (HU) and the risk of gout. METHODS: A comprehensive literature search up to June 2016, using PUBMED and EMBASE databases, was conducted to identify the relevant observational studies that examined the associations of tea consumption with the SUA level, HU and the risk of gout. RESULTS: A total of fifteen observational studies were included in this study, and nine studies were extracted for meta-analysis. For the SUA level, seven studies were included. According to the combined weighted mean difference (WMD), there was no significant difference between the highest and the lowest tea intake category in terms of the SUA level (WMD = 7.41 µmol/L, 95%CI: -2.34 to 17.15; P = 0.136). In subgroup analysis including three studies, green tea consumption was positively associated with the SUA level (WMD = 17.20 µmol/L, 95%CI: 7.00 to 27.40; P = 0.01). For the prevalence of HU, five studies were included. The overall multi-variable adjusted odds ratio (OR) for the highest versus the lowest category of tea consumption was 0.98 (95%CI: 0.77 to 1.24; P = 0.839). For the risk of gout, two prospective cohort studies showed that there was no relationship between tea consumption and the risk of gout in males and females, respectively. CONCLUSION: The current evidences suggest that tea consumption does not seem to be associated with the SUA level, HU and the risk of gout. However, due to the limited number of studies, green tea consumption might be positively associated with the SUA level. More well-designed prospective cohort studies are needed to elaborate these issues further.

Relationship between hyperuricemia and risk of coronary heart disease in a middle-aged and elderly Chinese population.

Objective To investigate the relationship between hyperuricemia and coronary heart disease (CHD) risk based on the Framingham risk score (FRS) in a middle-aged and elderly Chinese population. Methods This cross-sectional study enrolled patients undergoing routine check-ups at Xiangya Hospital between October 2013 and November 2014. Hyperuricemia was defined as uric acid ≥416 mmol/l for males and ≥360 mmol/l for females. A 10-year CHD risk was calculated from FRS. A multivariable logistic analysis model was used to evaluate associations. Results Of the 6347 patients, 3415 (53.8%) were male, 1543 (24.3%) had a CHD risk ≥10% (i.e. intermediate and high risk) and the prevalence of hyperuricemia was 18.1% ( n = 1148). After adjusting for potential confounding factors, the 10-year CHD risk was increased in patients with hyperuricemia compared with those without hyperuricemia by 0.28 times in the total population (odds ratio [OR] 1.28; 95% confidence interval [CI] 1.09, 1.48), by 0.25 times in the male population (OR 1.25; 95% CI 1.06, 1.47) and by 2.76 times in the female population (OR 3.76; 95% CI 2.08, 6.79). Conclusion Hyperuricemia was positively associated with a 10-year risk of CHD suggesting that it might be an independent CHD risk factor in middle-aged and elderly individuals.

Relationship between cigarette smoking and hyperuricemia in middle-aged and elderly population: a cross-sectional study.

The aim of the study was to estimate the cross-sectional association between cigarette smoking and the prevalence of hyperuricemia (HU) in the middle-aged and elderly males and females. A total of 3415 males and 2932 females were included in this study. HU was defined as SUA≥ 416 mmol/L for males and ≥360 mmol/L for females. The smoking status was classified into four categories based on daily smoking habit: (1) 0/day; (2) 1-10/day; (3) 11-20/day; and (4) >20/day. Multivariable logistic regressions were conducted to examine the aforementioned association. The prevalence of HU in the male and female sample was 25.0 and 10.0 %, respectively. In male subjects, the prevalence of HU in smokers (22.8 %) was significantly lower than that in non-smokers (26.5 %) (p = 0.016). Meanwhile, with adjustment for potential confounding factors, the prevalence of HU in smokers was still lower (OR = 0.83, 95 % CI 0.70-0.98, P = 0.033). Furthermore, a significantly inverse association between smoking status and HU was observed in the multivariable model. The multivariable-adjusted OR (95 % CI) for HU in the second, third and fourth category of smoking status was 0.84 (95 % CI 0.66-1.06), 0.90 (95 % CI 0.69-1.18) and 0.76 (95 % CI 0.58-0.99), respectively, compared with that in the first category. A clear trend (P for trend was 0.036) was observed. However, there was no significant association between cigarette smoking and HU in female subjects (P for trend was 0.739). This study indicated an inverse association between cigarette smoking and the prevalence of HU in the middle-aged and elderly male population, independent of some major confounding factors. The findings of this study expect further prospective studies to confirm the causal relationship.

Long noncoding RNAs in osteoarthritis.

Osteoarthritis (OA) is the most common form of arthritis that may affect all joint tissues. Unfortunately, the pathogenesis of OA is not fully understood yet and it cannot be cured totally. Long noncoding RNA (lncRNA) is a type of RNA molecule greater than 200 nucleotides, and deregulated expression of lncRNAs plays an important role in many types of inflammation-related diseases. In this review, we have focused on the association of lncRNAs in the development and progression of OA and the possibility of lncRNAs as a therapeutic agent for the treatment of OA. Some lncRNAs are up-regulated in OA cartilage, and plays a critical role in the degradation of chondrocyte extracellular matrix, consequently weakening the integrity of the articular cartilage. Therapeutic targeting of these lncRNAs has shown significant influence on controlling OA progression. More clinical studies are in focus for OA treatment strategy by targeting lncRNAs.

Associations of dietary and serum magnesium with serum high-sensitivity C-reactive protein in early radiographic knee osteoarthritis patients.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: The present study indicated that both dietary and serum Mg were inversely associated with serum hsCRP in early radiographic knee OA patients.

Single-dose intra-articular bupivacaine plus morphine versus bupivacaine alone after arthroscopic knee surgery: a meta-analysis of randomized controlled trials.

PURPOSE: The purpose of this meta-analysis was to compare the efficacy and safety of single-dose intra-articular bupivacaine plus morphine versus bupivacaine alone for pain management following arthroscopic knee surgery. METHOD: A comprehensive literature search was conducted to identify randomized controlled trials that used single-dose intra-articular bupivacaine plus morphine and bupivacaine alone for post-operative pain, using MEDLINE (1966-2014), Cochrane Library and EMBASE databases. The weighted mean difference (WMD), relative risk (RR) and their corresponding 95 % confidence intervals (CIs) were calculated using RevMan statistical software. RESULT: A total of twenty-nine trials (n = 1167) were included. The post-operative visual analog scale (VAS) pain score of the bupivacaine plus morphine group compared with the bupivacaine alone group was significantly lower (WMD -1.15, 95 % CI -1.67 to -0.63, p < 0.0001). As far as safety, there was no significant difference in side effects between the two groups (RR 1.10, 95 % CI 0.59-2.04, n.s.). Sensitivity analyses suggested that the results of these two primary outcomes were stable and reliable. However, the current evidence did not suggest a superior effect with respect to the time to first analgesic request (WMD 51.33, 95 % CI -110.99 to 213.65, n.s.) and the number of patients requiring supplementary analgesia (RR 1.13, 95 % CI 0.92-1.39, n.s.). CONCLUSIONS: On the basis of the currently available literature, this study is the first to suggest that single-dose intra-articular bupivacaine plus morphine was shown to be significantly better than bupivacaine alone at relieving post-operative pain after arthroscopic knee surgery without increasing the short-term side effects. Routine use of single-dose intra-articular bupivacaine plus morphine is an effective way for pain management after arthroscopic knee surgery. LEVEL OF EVIDENCE: II.

Analgesic effect and safety of single-dose intra-articular magnesium after arthroscopic surgery: a systematic review and meta-analysis.

To examine the analgesic effect and safety of single-dose intra-articular (IA) magnesium (Mg) after arthroscopic surgery. Pubmed, Embase and Cochrane library were searched through in January 2016. Eight RCTs and eight experimental studies were included. The IA Mg exhibited a significantly lower pain score when compared with placebo (MD, -0.41, 95% CI, -0.78 to -0.05, p = 0.03). There was no significant difference between Mg and bupivacaine in terms of pain relief and the time to first analgesic request. Furthermore, statistically significant differences both in pain score (MD, -0.62, 95% CI, -0.81 to -0.42, p < 0.00001) and time to first analgesic request (MD, 6.25, 95% CI, 5.22 to 7.29, p < 0.00001) were observed between Mg plus bupivacaine and bupivacaine alone. There was no statistically significant difference among the various groups with respect to adverse reactions. Most of the included in vitro studies reported the chondrocyte protective effect of Mg supplementation. There were also two in vivo studies showing the cartilage protective effect of IA Mg. The single-dose IA Mg following arthroscopic surgery was effective in pain relief without increasing adverse reactions, and it could also enhance the analgesic effect of bupivacaine. In addition, Mg seemed to possess the cartilage or chondrocyte protective effect based on experimental studies.

Phosphorylation of osteopontin has proapoptotic and proinflammatory effects on human knee osteoarthritis chondrocytes.

The aim of the present study was to investigate the effects of phosphorylated osteopontin (p-OPN) on apoptosis and pro-inflammatory cytokine expression in human knee osteoarthritis (OA) chondrocytes. Human knee OA chondrocytes obtained from patients who underwent total knee arthroplasty were treated with p-OPN, OPN or buffer. Reverse transcription quantitative-polymerase chain reaction (RT-qPCR) and western blot analysis were used to assess the expression levels of proinflammatory factors, including interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-6 and nuclear factor (NF)-κB. Apoptosis of human knee OA chondrocytes was detected by Annexin V-fluorescein isothiocyanate/propidium iodide flow cytometry. Compared with the controls, chondrocytes treated with OPN exhibited higher mRNA and protein expression levels of proinflammatory factors (IL-1ß, TNF-α, IL-6 and NF-κB), and a higher percentage of apoptotic chondrocytes. Furthermore, chondrocytes treated with p-OPN exhibited the highest mRNA and protein expression levels of proinflammatory factors (IL-1ß, TNF-α, IL-6, NF-κB) and the highest percentage of apoptotic chondrocytes. p-OPN induces chondrocyte apoptosis and proinflammatory factor release, which suggests that p-OPN may contribute to OA pathogenesis, and inhibition of p-OPN may provide a novel effective strategy to slow or halt OA progression.

Association among dietary magnesium, serum magnesium, and diabetes: a cross-sectional study in middle-aged and older adults.

BACKGROUND: A number of studies have reported the association between magnesium (Mg) and diabetes. However, the various conclusions were inconsistent and the data on the Chinese population was limited. The objective of this study was to evaluate the association among dietary Mg, serum Mg, and diabetes in Chinese adults. METHODS: A cross-sectional study that contained 2904 subjects was conducted. Biochemical test results and dietary intakes of subjects were collected for analysis. The adjusted odds ratios (ORs) and the corresponding 95 % confidence intervals (95 % CIs) were used to determine the relationship between Mg status and diabetes by logistic regression. RESULTS: The prevalence of diabetes of the investigated population was 10.1 %. Dietary Mg intake was not significantly correlated with diabetes (P > 0.05). The significant negative association between serum Mg and diabetes existed, and the multivariate adjusted OR was 0.34 (95 % CI 0.24, 0.49) in model 3 for the highest quartile of serum Mg compared with the lowest. The P values for trend were all less than 0.001 for the relationship between serum Mg and diabetes. Dietary Mg intake and serum Mg were not significantly correlated in the diabetes population (P = 0.936). CONCLUSIONS: Dietary Mg was not significantly correlated with diabetes, while serum Mg was inversely correlated with diabetes in the Chinese population. Meanwhile, dietary Mg intake and serum Mg were not significantly correlated in the diabetes population.