Adipokines regulate mesenchymal stem cell osteogenic differentiation.

Mesenchymal stem cells (MSCs) can differentiate into various tissue cell types including bone, adipose, cartilage, and muscle. Among those, osteogenic differentiation of MSCs has been widely explored in many bone tissue engineering studies. Moreover, the conditions and methods of inducing osteogenic differentiation of MSCs are continuously advancing. Recently, with the gradual recognition of adipokines, the research on their involvement in different pathophysiological processes of the body is also deepening including lipid metabolism, inflammation, immune regulation, energy disorders, and bone homeostasis. At the same time, the role of adipokines in the osteogenic differentiation of MSCs has been gradually described more completely. Therefore, this paper reviewed the evidence of the role of adipokines in the osteogenic differentiation of MSCs, emphasizing bone formation and bone regeneration.

Comparison of the Effectiveness of Simple Plate Fixation and Plate Combined with Local Fixation of Broken Ends in the Treatment of Oblique Fracture of Midshaft Clavicle.

OBJECTIVE: To compare the clinical efficacy of performing simple plate fixation with that using a plate combined with fracture end fixation to investigate the necessity of fracture end fixation outside the plate in cases of oblique fracture of the middle clavicle. METHODS: This was a retrospective follow-up study of patients with middle clavicle oblique fractures (Robinson types 2A1 and 2A2) between 2015 and 2020. Patients were divided into two groups according to their treatment options: the simple plate fixation (SPF) group (n = 79; 43 men and 36 women; average age, 46.37 ± 14.54 years) and the plate combined with fracture local fixation (PLFP) group (n = 81; 36 men and 45 women; average age, 48.42 ± 12.55 years). Intraoperative blood loss, operation time, postoperative fracture healing time, postoperative shoulder function score (Constant-Murley and disabilities of the arm, shoulder, and hand [DASH] scores), clinical complications, and postoperative subjective satisfaction were compared between the two groups. RESULTS: One hundred sixty patients with a sufficient follow-up period were included in the final analysis: 79 in the SPF group (follow-up time: 16.24 ± 3.94 months) and 81 in the PLFP group (follow-up time: 16.15 ± 3.43 months). Age, sex, body mass index, follow-up duration, fracture classification, and cause of injury were not significantly different between the two groups. There was no significant difference in blood loss, Constant-Murley and DASH scores, follow-up period, and postoperative subjective satisfaction between the two groups (P > 0.05). The fracture healing time was shorter in the PLFP group than in the SPF group (4.41 ± 0.99 vs. 4.87 ± 1.60 months, P < 0.05), but the operation duration was longer in the PLFP group than in the SPF group (65.48 ± 16.48 min, P < 0.05). There were seven (complication rate, 8.86%) and five (complication rate, 6.17%) cases that had complications in the SPF and PLFP groups, respectively. There was no significant difference in the complication rates between the two groups (P > 0.05). CONCLUSION: Although the healing time was shorter in the PLFP group than in the SPF group, the clinical efficiency of the two methods in the treatment of oblique fracture of the middle clavicle was similar.

Role of IL-17 gene polymorphisms in osteoarthritis: A meta-analysis based on observational studies.

BACKGROUND: Osteoarthritis (OA) is a chronic complex multifactorial joint disease, and a major degenerative form of arthritis. Existing studies on the association between polymorphisms of the IL-17 gene and the risk of OA in different populations have yielded conflicting findings. AIM: To investigate the association between polymorphisms of the IL-17 gene and the risk of OA. METHODS: We conducted a meta-analysis by systematically searching databases, including PubMed, EMBASE, MEDLINE, Cochrane Library, and Google Scholar to evaluate this association by calculating pooled odds ratios with 95% confidence intervals. Moreover, subgroup analyses stratified by ethnicity and OA type were also conducted. RESULTS: In a total of 6 citations involving 8 studies (2131 cases and 2299 controls), 4 single nucleotide polymorphisms were identified. Of these 4 polymorphisms, 2 (rs2275913, rs763780) were common in five case-control studies. Together, the pooled results revealed that the A allele and genotype AA/GA of the rs2275913 polymorphism, and the C allele and genotype CC of the rs763780 polymorphism in the IL-17 gene increased the risk of OA. Furthermore, stratification analyses by ethnicity and OA type showed that the rs2275913 polymorphism increased the risk of OA among Asians and in knee/hip OA, respectively. In addition, stratification analyses also revealed that the rs763780 polymorphism increased OA risk among both Asians and Caucasians in knee/hip OA. CONCLUSION: The rs763780 polymorphism of the IL-17F gene increased the risk of OA, whereas the rs2275913 polymorphism of the IL-17A gene increased the risk of OA only among Asians. Due to the limitations of this study, these findings should be validated in future studies.

Efficacy and Safety of Tranexamic Acid in Intertrochanteric Fractures: A Single-Blind Randomized Controlled Trial.

OBJECTIVE: To investigate the efficacy and safety of tranexamic acid (TXA) in the reduction of bleeding and the need for transfusion in elderly intertrochanteric fracture patients. METHODS: A total of 100 patients with intertrochanteric fractures undergoing surgery were enrolled and randomly allocated to the TXA group in which patients (75.10 ± 8.27 years old) were treated with 1 g of TXA, or the control group (77.82 ± 6.42 years old) treated with a placebo. Surgery was performed by two senior orthopaedic surgeons from two institutions. The proximal femoral nail antirotation (PFNA) was conducted using the standard procedure. Three outcome measures, including blood loss, transfusion, and complications, were recorded. Blood loss and transfusion were investigated to assess TXA's effectiveness, while complications were investigated to assess TXA's safety. Statistical indicators for blood loss included total, intraoperative, postoperative, and hidden blood loss volumes, calculated by hemoglobin levels, hematocrit levels, and drainage volume. The number and amount of blood transfusions were recorded. Complications associated with surgery, including deep vein thrombosis, pulmonary embolism, wound hematoma, wound infection, cardiovascular and cerebrovascular accidents, and respiratory infections, were also recorded. RESULTS: All patients were followed up for 1 month after surgery. There were no significant differences in demographic and clinical characteristics between the two groups. The TXA group suffered significantly less total blood loss (563.37 ± 197.51 vs 819.25 ± 273.96 mL, 95% CI: -349.49 to -162.27, P < 0.01), intraoperative blood loss (140.3 ± 80.64 vs 230.5 ± 130.56 mL, 95% CI -132.74 to -47.66, P < 0.01), and hidden blood loss (410.42 ± 178.23 vs 571.19 ± 218.13 mL, 95% CI: -238.85 to -82.69, P < 0.01) than the control group. However, postoperative total blood loss was not significantly different (97.5 ± 20.93 vs 94.7 ± 35.78 mL; P = 0.63). A total of 5 patients from the TXA group and 27 from the control group received packed RBC for postoperative transfusion, but the mean number of transfusion units was not significantly different between groups. Complications including deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic cerebral infarction, hematoma, and infection were observed in both groups, but no significant differences were found. CONCLUSIONS: In intertrochanteric fracture surgery performed using PFNA, intravenous administration of TXA significantly reduced the risk of intraoperative, total and hidden blood loss, in addition to the need for allogeneic transfusion, without increasing the rate of complications.

Efficacy and safety of tranexamic acid in elderly patients with intertrochanteric fracture: An updated meta-analysis.

BACKGROUND: Intertrochanteric fracture (ITF) is a common type of injury, and nearly 30% of ITF patients die in the first 12 mo, especially the elderly with limited activity. Tranexamic acid (TXA) has been widely used in reducing traumatic and surgical bleeding, however, the paucity of studies regarding its use in orthopedic trauma surgery has limited its integration into this field, which may benefit most from TXA. The safety of TXA in this group has not achieved a consensus. AIM: This meta-analysis was designed to investigate the efficacy and safety of TXA in elderly ITF patients undergoing surgery. METHODS: Databases, including Medline and PubMed, were searched for randomized controlled trials (RCTs) that were published before October 2018 and that addressed the efficacy and safety of TXA in patients who underwent ITF surgery. The Consolidated Standards of Reporting Trials 2010 Statement Checklist was used to assess the methodological quality of each study. Trials without and with heterogeneity were compared by fixed-effects analysis and random-effects analysis, respectively. For each study, odds ratio (OR) and 95%CI and mean differences and 95%CI were calculated for dichotomous and continuous outcomes, respectively. The Power and Sample Size Program software was used to calculate power and sample size. Stability of the results was assessed via sensitivity analysis. RESULTS: A total of 836 patients from eight RCTs were subjected to meta-analysis. TXA treatment compared with the control group significantly reduced postoperative blood loss (95%CI, -20.83 to -7.93 mL, P < 0.0001), hidden blood loss (95%CI, -213.67 to -64.43 mL, P = 0.0003), and total blood loss (95%CI, -332.49 to -23.18 mL, P = 0.02) by weighted mean differences of -14.38, -139.05, and -177.83 mL, respectively. However, no significant difference was observed between groups for analysis of intraoperative blood loss. The meta-analysis also proved that the usage of TXA in ITFs may not significantly increase the incidence of deep venous thrombosis. Allogeneic blood transfusion data showed that significantly fewer patients in the TXA group (42%) required transfusion than the control group (95%CI, 0.36 to 0.69; P < 0.0001). CONCLUSION: In ITF surgery, intravenous administration of TXA reduces the risk of hidden blood loss and the need for allogeneic transfusion, without increasing thrombotic risk.

Hinokitiol reduces matrix metalloproteinase expression by inhibiting Wnt/ß-Catenin signaling in vitro and in vivo.

OBJECTIVE: In this study, we investigated the effects of hinokitiol on matrix metalloproteinase (MMP)-1, -3, -13, collagen type II (Col2a1) and ß-catenin expressions in rat chondrocytes induced by interleukin-1ß and in an experimental rat model induced by intra-articular injection of mono-iodoacetate (MIA) into the knee. METHODS: Chondrocytes were cultured from the articular cartilage of 2-week-old rats. Passaged chondrocytes were pretreated with hinokitiol for 2h followed by co-incubation with IL-1ß for 24h. Quantitative real-time polymerase chain reaction and Western blotting were used to assess the expression of MMP-1, -3, -13, Col2a1 and ß-catenin. Chondrocytes were also treated with Licl, Dickkopf-1, and/or hinokitiol for 24h, the MMP-1, -3, -13 and ß-catenin protein levels determined by Western blotting. The in vivo effects of hinokitiol were assessed by morphological and histological analyses following MIA injection. RESULTS: Hinokitiol inhibited IL-1ß-stimulated MMP-1,-3 and -13 expressions and IL-1ß-induced activation of intracellular ß-catenin proteins in cultured chondrocytes. In vivo, morphological and histological examinations demonstrated that hinokitiol significantly ameliorated cartilage degeneration. CONCLUSIONS: Hinokitiol is an effective anti-inflammatory reagent that acts by inhibiting the Wnt/ß-catenin signaling pathway and could be a promising therapeutic agent for the prevention and treatment of osteoarthritis.

A possible mechanism in DHEA-mediated protection against osteoarthritis.

Dehydroepiandrosterone (DHEA) and its ester form, DHEA-S, are the most abundant steroids in human plasma. Our previous studies showed that DHEA protects against osteoarthritis (OA). The aim of this paper was to explore the possible mechanisms that underlie DHEA-mediated protection against OA. We tested the expression of ß-catenin, it was increased significantly in OA. Rabbit cartilage was treated with various concentrations of DHEA in both IL-1ß-induced rabbit chondrocytes and in rabbit cartilage from the anterior cruciate ligament transaction-induced OA model. We found DHEA decreased the expression of ß-catenin. Then we further activated Wnt/ß-catenin signaling by ß-catenin transfection and inactivated it by the inhibitor Dickkopf1 in chondrocytes to reveal its role in the pathogenesis of OA. It turns out the protective effect of DHEA was significantly decreased when Wnt/ß-catenin signaling was activated, while inactivating Wnt/ß-catenin signaling enhanced the effects of DHEA. Therefore, we hypothesize that DHEA probably exerted its chondroprotective effect by regulating Wnt/ß-catenin signaling. Our findings demonstrate the critical role of Wnt/ß-catenin signaling in DHEA-mediated protection against OA.

Tetrandrine induces apoptosis and triggers a caspase cascade in U2-OS and MG-63 cells through the intrinsic and extrinsic pathways.

Although neoadjuvant chemotherapy has improved the survival rate of osteosarcoma patients, drug resistance remains a predominant obstacle to improving efficacy and necessitates the development of novel chemotherapeutical agents. The aim of this study was to investigate whether tetrandrine (TET) induces apoptosis in the U-2OS and MG-63 osteosarcoma cell lines and to further determine the underlying mechanism. This study investigated the effects of TET on osteosarcoma in vitro. To examine the antitumor effects of TET on osteosarcoma, the two osteosarcoma cell lines were treated with TET and subjected to apoptosis assays. The results revealed that TET induced the apoptosis of osteosarcoma cells in a time- and dose-dependent manner. Furthermore, the apoptosis of osteosarcoma cells was accompanied by increased cytochrome c (Cyto-C), apoptotic protease-activating factor (Apaf)-1, Bid and Bax activation and reduced Bcl-2 and Bcl-xl activation, demonstrating that the apoptosis may have occurred through the mitochondrial pathway. In conclusion, the results suggest that TET is a promising agent for osteosarcoma therapy.

Do we really need closed-suction drainage in total hip arthroplasty? A meta-analysis.

PURPOSE: The clinical use of closed-suction drainage, which aims to reduce postoperative wound haematomas and infection, is common. This study was performed to determine whether closed-suction drainage is safe and effective in promoting wound healing and reducing blood loss and other complications compared with no-drainage in total hip arthroplasty. METHODS: The literature search was based on PubMed, the Cochrane Library, MEDLINE, and EMBASE. The data were evaluated using the generic evaluation tool designed by the Cochrane Bone, Joint and Muscle Trauma Group, and then analysed using RevMan 5.0. Twenty randomised controlled trials involving 3,186 patients were included in our analysis. RESULTS: The results of our meta-analysis indicate that closed-suction drainage reduces the requirement for dressing reinforcement, but increases the rate of homologous blood transfusion. No significant difference was observed in the incidence of infection, blood loss, changes in haemoglobin and haematocrit, functional assessment, or other complications when the drainage group was compared with the no-drainage group. CONCLUSIONS: Our results of the comparison between closed-suction drainage and no drainage in THA have indicated that the routine use of closed-suction drainage for elective total hip arthroplasty may be of more harm than benefit.

Do we really need tranexamic acid in total hip arthroplasty? A meta-analysis of nineteen randomized controlled trials.

BACKGROUND: Studies have shown that tranexamic acid reduces blood loss and transfusion need in patients undergoing total hip arthroplasty. However, no to date, no study has been large enough to determine definitively whether the drug is safe and effective. We examined whether intravenous tranexamic acid, when compared with placebo, was safe and effective in total hip arthroplasty. METHODS: The literature search was conducted using the PubMed, Cochrane Library, MEDLINE, EMBASE, and China National Knowledge Infrastructure (CNKI) databases. Data were evaluated using the generic evaluation tool designed by the Cochrane Bone, Joint and Muscle Trauma Group. Ultimately, 19 randomized controlled trials involving 1,030 patients were included. RESULTS: The use of tranexamic acid significantly reduced total blood loss by a mean of 305.27 mL [95 % confidence interval (CI) -397.66 to -212.89, p < 0.001], intraoperative blood loss by a mean of 86.33 mL(95 % CI -152.29 to -20.37, p = 0.01), postoperative blood loss by a mean of 176.79 mL (95 % CI -236.78 to -116.39, p < 0.001), and "hidden" blood loss by a mean of 152.70 mL (95 % CI -187.98 to -117.42, p < 0.001), resulting in a meaningful reduction in the proportion of patients requiring blood transfusion (odds ratio 0.28, 95 % CI 0.19 to 0.42, p < 0.001). There was no significant difference in occurrence of deep vein thrombosis, pulmonary embolism, or other complications among the study groups, or cost or hospitalization duration. CONCLUSIONS: The data from this meta-analysis indicate that intravenous tranexamic acid may reduce blood loss and transfusion need in patients undergoing total hip arthroplasty without increasing the risk of complications. However, high-quality randomized controlled trials are required to validate the results.