Pengfei Lei

Antitumor effect of resveratrol on chondrosarcoma cells via phosphoinositide 3-kinase/AKT and p38 mitogen-activated protein kinase pathways

Chondrosarcoma is one of the most common types of primary bone cancer that develops in cartilage cells. Resveratrol (Res), a natural polyphenol compound isolated from various fruits, has a suppressive effect on various human malignancies. It has been shown that Res inhibits matrix metalloproteinase (MMP)-induced differentiation in chondrosarcoma cells. However, the effects of Res on cell proliferation, apoptosis and invasion of chondrosarcoma cells, as well as the underlying mechanisms, remain largely unknown. To the best of our knowledge, the present study showed for the first time that Res inhibited proliferation and induced apoptosis in chondrosarcoma cells in a dose-dependent manner. Furthermore, it was shown that Res also suppressed chondrosarcoma cell invasion in a dose-dependent manner, probably via the inhibition of MMP2 and MMP9 protein expression. Molecular mechanism investigations revealed that Res could inhibit the activity of phosphoinositide 3-kinase/AKT and p38 mitogen-activated protein kinase signaling pathways, which has been demonstrated to be important in the regulation of proliferation, apoptosis and invasion in various cancer cell types. In conclusion, this study suggests that Res may serve as a promising agent for the treatment of chondrosarcoma.

Greater Trochanter Osteotomy With Cementless THA for Crowe Type IV DDH

This study explored the surgical method and short-term clinical effect of a greater trochanter osteotomy along with cementless artificial total hip arthroplasty in the treatment of Crowe type IV developmental dysplasia of the hip. The authors conducted a retrospective analysis of 18 patients (22 hips) with Crowe type IV dysplasia who were seen between June 2008 and August 2010. After undergoing cementless artificial total hip arthroplasty using a posterolateral approach, a greater trochanter osteotomy was used to adjust the tension of the gluteal muscle, and an acetabular cup was placed. Average preoperative length shortening of the affected limb was 4.5 cm (range, 3.4-6 cm), and average postoperative length increase was 4.0 cm (range, 3.2-4.8 cm). Average postoperative Harris Hip Score was 87 (range, 79-91), which was higher than the average preoperative score of 38 (range, 32-51). Intraoperatively, 3 hips (3 patients) sustained a proximal femur fracture. Due to the stability of the femoral prosthesis, either no treatment or wire fixation only was given; by 2 months postoperatively, radiographs indicated that all fractures had healed. One patient had symptoms of sciatic nerve paralysis that resolved 3 months postoperatively. Performing a greater trochanter osteotomy after cementless artificial total hip arthroplasty is effective for the treatment of Crowe type IV dysplasia and can rebuild the complex biology and biomechanics of hip dysplasia without increasing the complication risk.

Expression of hypoxia-inducible factor-1α in synovial fluid and articular cartilage is associated with disease severity in knee osteoarthritis

The aim of the present study was to examine hypoxia-inducible factor 1α (HIF-1α) levels in the synovial fluid and articular cartilage of patients with primary knee osteoarthritis (OA) and to investigate their association with the severity of disease. A total of 36 patients with knee OA and ten healthy controls were enrolled. Anteroposterior knee radiographs and/or Mankin scores were assessed to determine the disease severity of the affected knee. Radiographic grading of OA in the knee was performed according to Kellgren-Lawrence criteria. HIF-1α levels in synovial fluid were measured using enzyme-linked immunosorbent assay, whereas HIF-1α levels in articular cartilage were assessed with immunohistochemical methods. Compared with healthy controls, OA patients exhibited an increased HIF-1α concentration in synovial fluid (218.17±25.12 vs. 156.66±7.74 pg/ml; P<0.001) and articular cartilage (P<0.05). Furthermore, synovial fluid HIF-1α levels demonstrated a positive correlation with articular cartilage HIF-1α levels (Pearsons P=0.815; P<0.001). Subsequent analysis showed that synovial fluid HIF-1α levels were significantly correlated with the severity of disease (Spearmans ρ=0.933; P<0.001). Furthermore, articular cartilage levels of HIF-1α also correlated with disease severity (Spearmans ρ=−0.967; P<0.001). The findings of the present study suggested that HIF-1α in synovial fluid and articular cartilage is associated with progressive joint damage and is likely to be a useful biomarker for determining disease severity and progression in knee OA.

A New Method for Xenogeneic Bone Graft Deproteinization: Comparative Study of Radius Defects in a Rabbit Model.

Background and Objectives Deproteinization is an indispensable process for the elimination of antigenicity in xenograft bones. However, the hydrogen peroxide (H2O2) deproteinized xenograft, which is commonly used to repair bone defect, exhibits limited osteoinduction activity. The present study was designed to develop a new method for deproteinization and compare the osteogenic capacities of new pepsin deproteinized xenograft bones with those of conventional H2O2 deproteinized ones. Methods Bones were deproteinized in H2O2 or pepsin for 8 hours. The morphologies were compared by HE staining. The content of protein and collagen I were measured by the Kjeldahl method and HPLC-MS, respectively. The physical properties were evaluated by SEM and mechanical tests. For in vivo study, X-ray, micro-CT and HE staining were employed to monitor the healing processes of radius defects in rabbit models transplanted with different graft materials. Results Compared with H2O2 deproteinized bones, no distinct morphological and physical changes were observed. However, pepsin deproteinized bones showed a lower protein content, and a higher collagen content were preserved. In vivo studies showed that pepsin deproteinized bones exhibited better osteogenic performance than H2O2 deproteinized bones, moreover, the quantity and quality of the newly formed bones were improved as indicated by micro-CT analysis. From the results of histological examination, the newly formed bones in the pepsin group were mature bones. Conclusions Pepsin deproteinized xenograft bones show advantages over conventional H2O2 deproteinized bones with respect to osteogenic capacity; this new method may hold potential clinical value in the development of new biomaterials for bone grafting.

Effect of posterior cruciate ligament rupture on the radial displacement of lateral meniscus

BACKGROUND The relationship between lateral meniscus tear and posterior cruciate ligament injury is not well understood. The present study aims to investigate and assess the effect of posterior cruciate ligament rupture on lateral meniscus radial displacement at different flexion angles under static loading conditions. METHODS Twelve fresh human cadaveric knee specimens were divided into four groups such as posterior cruciate ligament intact, anterolateral band rupture, posteromedial band rupture and posterior cruciate ligament complete rupture groups, according to the purpose and order of testing. Radial displacement of lateral meniscus was measured under different loads (200-1000N) at 0°, 30°, 60°, and 90° of knee flexion. FINDINGS Compared with posterior cruciate ligament intact group, the displacement values of lateral meniscus in anterolateral band rupture group increased at 0° flexion with 600N, 800N, and 1000N and at 30°, 60° and 90° flexion under all loading conditions. Posteromedial band rupture group exhibited higher displacement at 0° flexion under all loading conditions, at 30° and 60° flexion with 600, 800N and 1000N, and at 90° flexion with 400N, 600N, 800N, and 1000N than the posterior cruciate ligament intact group. The posterior cruciate ligament complete rupture group had a higher displacement value of lateral medial meniscus at 0°, 30°, 60° and 90° flexion under all loading conditions, as compared to the posterior cruciate ligament intact group. INTERPRETATION The study concludes that partial and complete rupture of the posterior cruciate ligament can trigger the increase of radial displacement on lateral meniscus.

Small interfering RNA-induced silencing of galectin-3 inhibits the malignant phenotypes of osteosarcoma in vitro

Osteosarcoma (OS) is the most common malignant tumor of bone. It has recently been demonstrated that galectin-3, a multifunctional β-galactoside-binding, is significantly upregulated in OS tissues, and is correlated with its progression and metastasis. However, the detailed role of galectin‑3 in the regulation of cellular biological processes in OS cells has remained to be elucidated. The present study reported that the mRNA and protein levels of galectin‑3 were significantly increased in OS tissues compared to those in their matched normal adjacent tissues. Furthermore, galectin‑3 was upregulated in three OS cell lines, Saos‑2, MG63 and U2OS, when compared with that in the human osteoblast cell line hFOB1.19. Knockdown of galectin‑3 by galectin‑3‑specific small interfering RNA markedly inhibited OS‑cell proliferation and induced cell apoptosis. Furthermore, silencing of galectin‑3 expression significantly inhibited OS cell migration and invasion, accompanied with a marked decrease in the protein expression of matrix metalloproteinase 2 and ‑9. Mechanistic investigation suggested that the mitogen‑activated protein kinase kinase/extracellular signal‑regulated protein kinase signaling pathway may be involved in the galectin‑3‑mediated OS cell invasion. In conclusion, the present study was the first to report that silencing of galectin‑3 inhibited the malignant phenotypes of osteosarcoma in vitro. Therefore, galectin-3 may serve as a potential therapeutic target for OS.

Knockdown of PREX2a inhibits the malignant phenotype of osteosarcoma cells.

Phosphatidylinositol‑3,4,5‑trisphosphate‑dependent Rac exchange factor 2a (PREX2a), which is a regulator of the small guanosine triphosphatase Rac, has recently been reported to have an oncogenic role via the suppression of phosphatase and tensin homolog deleted on chromosome ten (PTEN) activity, and the subsequent activation of phosphoinositide 3‑kinase (PI3K) signaling. However, the detailed role of PREX2a in osteosarcoma (OS) remains unclear. Reverse transcription quantitative polymerase chain reaction and western blotting was used to detect mRNA and protein levels. MTT assay was performed to examine cell proliferation and a Transwell assay and wound healing assay were conducted to examine cell invasion and migration. The present study demonstrated that PREX2a was markedly upregulated in OS cell lines, as compared with in normal osteoblast hFOB1.19 cells. In addition, knockdown of PREX2a expression significantly inhibited OS cell proliferation, whereas overexpression of PREX2a markedly promoted OS cell proliferation. Inhibition of PREX2a also markedly suppressed the invasion and migration of OS cells, at least partly by suppressing the protein expression of matrix metalloproteinase (MMP)2 and MMP9. Conversely, upregulation of PREX2a enhanced OS cell invasion and migration. In addition, PI3K signaling activity was significantly reduced following knockdown of PREX2a, and this was accompanied by an upregulation of PTEN activity. The results of the present study suggested that PREX2a may act as an oncogene in OS via the inhibition of PTEN activity and activation of PI3K signaling.

Efficacy and safety of tranexamic acid in total hip replacement: A PRISMA-compliant meta-analysis of 25 randomized controlled trials

Background: Hip osteoarthritis is one of the most prevalent musculoskeletal degenerative diseases in elderly. Total hip arthroplasty (THA) is the most effective surgical treatment for end stage hip osteoarthritis. Tranexamic acid (TA) is a potent drug to reduce surgical blood loss in surgery, therefore, as a potential drug for application in THA. Objectives: To identify the combined efficacy of TA administration in THA. A meta-analysis including 25 randomized controlled trials was conducted for generating synthesized effects. Methods: This meta-analysis followed the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines for reporting systematic reviews and meta-analysis. A total of 25 Randomized controlled trials (RCTs) were included for meta-analysis. Results: The pooled results illustrated that total blood loss, intraoperative blood loss, postoperative blood loss, hemoglobin drop, transfusion rate, and average hospital stay were significantly lower than controls (standardized mean difference or odds ratio (OR) (95%CI): −0.87, (−1.13,−0.61), −0.68, (−0.96,−0.39), −1.41, (−2.24,−0.59), −1.11, (−1.63,−0.58), 0.28, (0.20,−0.38), −0.17, (−0.49,0.14), P < .05, respectively). Moreover, TA acts efficiently without increasing risk of thromboembolic events with OR = 1.14, 95%CI = 0.50–2.62, P = .75. Subgroup analysis indicated no statistically significant differences between a higher dose of topical TA (≥2 g or 15 mg/kg) or a lower dose (<2 g or 15 mg/kg). Conclusion: The findings indicated that TA is clinically effective and safe in patients receiving total hip arthroplasty.

Prognosis of Advanced Tenosynovial Giant Cell Tumor of the Knee Diagnosed During Total Knee Arthroplasty

BACKGROUND Tenosynovial giant cell tumor (TGCT) is a relatively rare disease often misdiagnosed as osteoarthritis. Synovectomy or arthroplasty is the recommended treatment option, but recurrence is common after surgery. This study aimed to determine the prognosis of patients with advanced TGCT that was diagnosed incidentally during total knee arthroplasty (TKA) for osteoarthritis and treated by synovectomy. METHODS From January 2008 to July 2011, TGCT was diagnosed incidentally in 10 patients (a total of 11 individual knees) undergoing posterior-stabilized TKA for an initial diagnosis of osteoarthritis. TGCT was confirmed by histopathology of biopsy specimens. Partial synovectomy was performed for localized-type TGCT (3 knees, 3 patients) and total synovectomy for diffuse-type TGCT (8 knees, 7 patients). RESULTS All patients were female with a mean age of 61.7 ± 6.6 (range 50-70) years. No postoperative infection, nerve injury, or deep venous thrombosis occurred. All patients were followed up for a mean period of 60.9 ± 6.6 (39-83) months, and no recurrence of TGCT occurred. X-ray imaging showed no apparent radiolucent lines around the prosthesis, and no prosthetic loosening, subsidence, or osteolysis. The joints were stable, with a significantly improved range of motion following surgery (109.5° ± 8.8° vs 80.5° ± 16.8°, P < .01). The Knee Society scores for knee joint (90.0 ± 4.1 vs 40.5 ± 8.1) and knee function (81.8 ± 7.5 vs 35.0 ± 13.8) were both significantly improved after surgery (P < .01). CONCLUSION Inactive TGCT could not be diagnosed preoperatively. TKA combined with synovectomy is effective in the treatment of advanced TGCT with degenerative lesions.

Role of RANK and Akt1 activation in human osteosarcoma progression: A clinicopathological study

The receptor activator of nuclear factor κB (RANK) axis is the fundamental signaling pathway in bone formation as well as bone tumor pathophysiology. The aim of the present study was to evaluate the impact of the expression of RANK and its downstream signaling molecule Akt1 on tumor progression in patients with osteosarcoma. Expression of RANK and Akt1 was examined in 78 human osteosarcoma samples by immunohistochemistry using formalin-fixed samples. Following this, each graded immunohistochemistry result was correlated with clinicopathological parameters and patient survival. In total, 60 osteosarcomas (76.9%) expressed RANK and 58 cases (74.4%) showed expression of Akt1. In addition, expression of RANK was negatively correlated with disease-free survival by Kaplan-Meier analysis. A resistance was observed to chemotherapy in RANK-expressing cases, which was statistically significant (P<0.05). In addition, chemotherapy and staging of the tumor were found to independent factors that have an effect on patient survival (P<0.05). Thus, RANK was identified as a negative prognostic factor of osteosarcoma survival.