Osteoarthritis (OA) is a common degenerative disease. PA28γ is a member of the 11S proteasome activator and is involved in the regulation of several important cellular processes, including cell proliferation, apoptosis, and inflammation. This study aimed to explore the role of PA28γ in the occurrence and development of OA and its potential mechanism. A total of 120 newborn male mice were employed for the isolation and culture of primary chondrocytes. OA-related indicators such as anabolism, catabolism, inflammation, and apoptosis were detected. Effects and related mechanisms of PA28γ in chondrocyte endoplasmic reticulum (ER) stress were studied using western blotting, real-time polymerase chain reaction (PCR), and immunofluorescence. The OA mouse model was established by destabilized medial meniscus (DMM) surgery, and adenovirus was injected into the knee cavity of 15 12-week-old male mice to reduce the expression of PA28γ. The degree of cartilage destruction was evaluated by haematoxylin and eosin (HE) staining, safranin O/fast green staining, toluidine blue staining, and immunohistochemistry.Aims
Methods
Rotator cuff muscle atrophy and fatty infiltration affect the clinical outcomes of rotator cuff tear patients. However, there is no effective treatment for fatty infiltration at this time. High-intensity interval training (HIIT) helps to activate beige adipose tissue. The goal of this study was to test the role of HIIT in improving muscle quality in a rotator cuff tear model via the β3 adrenergic receptor (β3AR). Three-month-old C57BL/6 J mice underwent a unilateral rotator cuff injury procedure. Mice were forced to run on a treadmill with the HIIT programme during the first to sixth weeks or seventh to 12th weeks after tendon tear surgery. To study the role of β3AR, SR59230A, a selective β3AR antagonist, was administered to mice ten minutes before each exercise through intraperitoneal injection. Supraspinatus muscle, interscapular brown fat, and inguinal subcutaneous white fat were harvested at the end of the 12th week after tendon tear and analyzed biomechanically, histologically, and biochemically.Aims
Methods
Residual tumor cells left in the bone defect after malignant bone tumor resection can result in local tumor recurrence and high mortality. Therefore, ideal bone filling materials should not only aid bone reconstruction or regeneration, but also exert local chemotherapeutic efficacy. However, common bone substitutes used in clinics are barely studied in research for local delivery of chemotherapeutic drugs. Here, we aimed to use facile manufacturing methods to render polymethylmethacrylate (PMMA) cement and ceramic granules suitable for local delivery of cisplatin to limit bone tumor recurrence. Porosity was introduced into PMMA cement by adding 1-4% carboxymethylcellulose (CMC) containing cisplatin, and chemotherapeutic activity was rendered to two types of granules via adsorption. Then, mechanical properties, porosity, morphology, drug release kinetics, The mechanical strengths of PMMA-based cements were sufficient for tibia reconstruction at CMC contents lower than 4% (≤3%). The concentrations of released cisplatin (12.1% and 16.6% from PMMA with 3% and 4% CMC, respectively) were sufficient for killing of osteosarcoma cells, and the fraction of dead cells increased to 91.3% within 7 days. Functionalized xenogeneic granules released 29.5% of cisplatin, but synthetic CaP granules only released 1.4% of cisplatin over 28 days. The immobilized and released cisplatin retained its anti-cancer efficacy and showed dose-dependent cytostatic effects on the viability of metastatic bone tumor cells. Bone substitutes can be rendered therapeutically active for anticancer efficacy by functionalization with cisplatin. As such, our data suggest that multi-functional PMMA-based cements and cisplatin-loaded granules represent viable treatment options for filling bone defects after bone tumor resection.
Rheumatoid arthritis (RA) is a common chronic immune disease. Berberine, as its main active ingredient, was also contained in a variety of medicinal plants such as Berberaceae, Buttercup, and Rutaceae, which are widely used in digestive system diseases in traditional Chinese medicine with anti-inflammatory and antibacterial effects. The aims of this article were to explore the therapeutic effect and mechanism of berberine on rheumatoid arthritis. Cell Counting Kit-8 was used to evaluate the effect of berberine on the proliferation of RA fibroblast-like synoviocyte (RA-FLS) cells. The effect of berberine on matrix metalloproteinase (MMP)-1, MMP-3, receptor activator of nuclear factor kappa-Β ligand (RANKL), tumour necrosis factor alpha (TNF-α), and other factors was determined by enzyme-linked immunoassay (ELISA) kit. Transcriptome technology was used to screen related pathways and the potential targets after berberine treatment, which were verified by reverse transcription-polymerase chain reaction (RT-qPCR) and Western blot (WB) technology.Aims
Methods
Pellino1 (Peli1) has been reported to regulate various inflammatory diseases. This study aims to explore the role of Peli1 in the occurrence and development of osteoarthritis (OA), so as to find new targets for the treatment of OA. After inhibiting Peli1 expression in chondrocytes with small interfering RNA (siRNA), interleukin (IL)-1β was used to simulate inflammation, and OA-related indicators such as synthesis, decomposition, inflammation, and apoptosis were detected. Toll-like receptor (TLR) and nuclear factor-kappa B (NF-κB) signalling pathway were detected. After inhibiting the expression of Peli1 in macrophages Raw 264.7 with siRNA and intervening with lipopolysaccharide (LPS), the polarization index of macrophages was detected, and the supernatant of macrophage medium was extracted as conditioned medium to act on chondrocytes and detect the apoptosis index. The OA model of mice was established by destabilized medial meniscus (DMM) surgery, and adenovirus was injected into the knee cavity to reduce the expression of Peli1. The degree of cartilage destruction and synovitis were evaluated by haematoxylin and eosin (H&E) staining, Safranin O/Fast Green staining, and immunohistochemistry.Aims
Methods
We have previously reported cryoablation-assisted joint-sparing surgery for osteosarcoma with epiphyseal involvement. However, it is not clear whether this is a comparable alternative to conventional joint arthroplasty in terms of oncological and functional outcomes. A total of 22 patients who had localized osteosarcoma with epiphyseal involvement around the knee and underwent limb salvage surgery were allocated to joint preservation (JP) group and joint arthroplasty (JA) group. Subjects were followed with radiographs, Musculoskeletal Tumor Society (MSTS) score, and clinical evaluations at one, three, and five years postoperatively.Aims
Methods
Rheumatoid arthritis (RA), which mainly results from fibroblast-like synoviocyte (FLS) dysfunction, is related to oxidative stress. Advanced oxidation protein products (AOPPs), which are proinflammatory mediators and a novel biomarker of oxidative stress, have been observed to accumulate significantly in the serum of RA patients. Here, we present the first investigation of the effects of AOPPs on RA-FLSs and the signalling pathway involved in AOPP-induced inflammatory responses and invasive behaviour. We used different concentrations of AOPPs (50 to 200 µg/ml) to treat RA-FLSs. Cell migration and invasion and the expression levels of tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), and MMP-13 were investigated. Western blot and immunofluorescence were used to analyze nuclear factor-κB (NF-κB) activation.Aims
Methods
Spinal metastases are seen in 10–30% of cancer patients. Twenty percent of these metastases occur in the lumbo-sacral spine. Lumbo-sacral spine has different mechanical properties and encloses the cauda equina. Few studies took interest in this spinal segment. The objective of this study is to evaluate prognostic factors of lumbo-sacral spinal metastasis treated in our center. We retrospectively reviewed 376 patients who were operated in our center from 2010 to 2018. Eighty-nine patients presented lumbo-sacral metastases and thus were included. Data collected included age, smoking, tumor histology, American spinal injury association (ASIA) score, modified Tokuhashi score, modified Bauer score, ambulation status and adjuvant treatment. The mean population age was 60.9 years old (35–85). The tumor histology was predominantly lung (19 patients, 21.3%), breast (13 patients, 14.6%), kidney (11 patients, 12.4%) and prostate (9 patients 10.1%). Twenty-two patients (24.7%) were unable to walk preoperatively. Seventy-nine patients (88.8%) underwent a posterior open approach with corpectomy in 65 patients (73%). Eighteen patients regained ambulation post-operatively (81.8%). The mean survival was 24.03 months (CI95% 17,38–30,67, Range 0–90) and the median of survival was 9 months (CI95% 4.38–13.62). Better preoperative ASIA score had a significant favorable effect (p=0.03) on survival. Patients who regained their ability to walk had better survival (25.1 months (CI95% 18.2–32) VS 0.5 months (CI95% 0–1.1). Postoperative radiotherapy had a benefic effect on survival (p=0.019): Survival Increased from 10.5 months (CI95% 2.4–18.7) to 27.6 months (CI95% 19.5–35.8). The modified Tokuhashi and the modified Bauer scores underestimated the survival of the patients with lumbosacral metastases. Lumbosacral spinal metastases has better survival than expected by Tokuhashi and Bauer score. Surgical procedure have an important impact on survival and the ability to walk.
Evaluate the complications and outcomes of off-hours spinal metastasis surgery. Retrospective analysis of a prospective collected data. Preoperative, operative and post-operative data were collected as well as the complications and Frankel score at all time checkpoints. Off-hours surgery was defined as surgery starting between 17:00 and 8:00 the following day or surgery during the weekend. p < 0 .05 was defined as statistical significance threshold. 376 patients were included with an incidence of off-hours surgery of 32%. There was an increase of neurologic complication in the off hours group. This was associated with a higher ASA score and older population group. Oddly, there was decreased operative time with off-hours surgery with no difference in bleeding and number of fusion levels. Nonetheless, there was a higher percentage of neurologic improvement with off hours surgery compared to in-hours surgery. Finally, there were no effect on patients' survival in this patient population. To our knowledge, this is the first report of the effect of off-hours surgery on complications and outcomes of spinal metastasis. Greater neurological compromise and higher age and ASA scores were associated with higher incidence of off-hours surgery. It is associated with decreased surgical time with higher percentage of neurological improvement. Finally, there is no effect of surgical timing on survival rates.
Many biomechanical studies have shown that the weakest biomechanical point of a rotator cuff repair is the suture-tendon interface at the medial row. We developed a novel double rip-stop (DRS) technique to enhance the strength at the medial row for rotator cuff repair. The objective of this study was to evaluate the biomechanical properties of the DRS technique with the conventional suture-bridge (SB) technique and to evaluate the biomechanical performance of the DRS technique with medial row knots. A total of 24 fresh-frozen porcine shoulders were used. The infraspinatus tendons were sharply dissected and randomly repaired by one of three techniques: SB repair (SB group), DRS repair (DRS group), and DRS with medial row knots repair (DRSK group). Specimens were tested to failure. In addition, 3 mm gap formation was measured and ultimate failure load, stiffness, and failure modes were recorded.Aims
Methods
The use of frozen tumour-bearing autograft combined with a vascularized fibular graft (VFG) represents a new technique for biological reconstruction of massive bone defect. We have compared the clinical outcomes between this technique and Capanna reconstruction. From June 2011 to January 2016 a retrospective study was carried out of patients with primary osteosarcoma of lower limbs who underwent combined biological intercalary reconstruction. Patients were categorized into two groups based on the reconstructive technique: frozen tumour-bearing autograft combined with concurrent VFG (Group 1) and the Capanna method (Group 2). Demographics, operating procedures, oncological outcomes, graft union, limb function, and postoperative complications were compared.Aims
Methods
Core decompression (CD) is effective to relieve pain and delay the advent of total hip arthroplasty (THA) for osteonecrosis of the femoral head (ONFH). However, the influence of CD on the subsequent THA has not been determined yet. Literatures published up to and including November 2018 were searched in PubMed, Embase and the Cochrane library databases with predetermined terms. Comparative studies of the clinical outcomes between conversion to THA with prior CD (the Prior CD group) and primary THA (the Control group) for ONFH were included. Data was extracted systematically and a meta- analysis was performed.Background
Methods
Ubiquitin E3 ligase-mediated protein degradation regulates osteoblast function. Itch, an E3 ligase, affects numerous cell functions by regulating ubiquitination and proteasomal degradation of related proteins. However, the Itch-related cellular and molecular mechanisms by which osteoblast differentiation and function are elevated during bone fracture repair are as yet unknown. We examined the expression levels of E3 ligases and NF-κB members in callus samples during bone fracture repair by quantitative polymerase chain reaction (qPCR) and the total amount of ubiquitinated proteins by Western blot analysis in wild-type (WT) mice. The expression levels of osteoblast-associated genes in fracture callus from Itch knockout (KO) mice and their WT littermates were examined by qPCR. The effect of NF-κB on Itch expression in C2C12 osteoblast cells was determined by a chromatin immunoprecipitation (ChIP) assay.Objectives
Methods
Soft tissue tension and intra-articular pressure distribution plays a crucial role in postoperative function and survivorship of TKA prosthesis. Although posterior stabilized (PS) and cruciate retaining (CR) knees have both been successful in relieving pain and restore function, it is reported that the joint gaps were significantly distinct between the two designs during flexion. The aim of this study is to find out what is the difference in intra-articular pressure distribution between PS and CR knees. We prospectively included 45 consecutive patients (50 knees) scheduled for total knee arthroplasty between August, 2013 and April, 2014 in our hospital. 23 patients (25 osteoarthritic knees) received a Genesis II CR TKA (Smith & Nephew, Memphis, USA), and the other 22 patients (25 osteoarthritic knees) received Genesis II PS TKA (Smith & Nephew, Memphis, USA). During operation, after the bone osteotomy and soft tissue balance were completed, we measured and compared the intra-articular pressure distribution at 0°, 30°, 45°, 60°, 90°, and 120° flexion with a previously validated “Wireless Force Measurement System (WFMS)”. Joint gaps were measured at extension and 90° flexion. The soft tissue was not considered balanced until the medial and lateral joint gap difference ≤ 2mm at extension and 90° flexion. There are no significant differences in age, gender, BMI, varus angle and flexion deformity, and preoperative range of motion between the two groups. The medial-lateral pressure distribution and total pressure were compared at different angles between CR and PS knees.Background
Methods
The data regarding the effects of noggin on bone morphogenetic protein (BMP)-induced osteogenesis of mesenchymal stem cells (MSCs) are controversial. Most studies performed in rodent cells/models indicated that noggin was a negative regulator of BMP-2-induced osteogenesis; however, one study conducted with human MSCs in culture showed that the addition of noggin induced osteogenesis in vitro. To clear the controversy, we designed this study to evaluate the effects of knocking down noggin gene expression on BMP-2-induced osteogenesis of human bone marrow-derived primary MSCs in vitro. MSCs were isolated from human tibial bone marrow by density gradient centrifugation. Two noggin small interfering RNAs (siRNAs) were used in this study to knockdown noggin gene expression. There were four study groups: MSCs with no transfection of siRNA (named as NT group), MSCs transfected with non-targeting negative control siRNA (named as control group), MSCs transfected with noggin siRNA1 (named as NOGsi1 group), and MSCs transfected with noggin siRNA2 (named as NOGsi2 group). After transfection, MSCs were induced to undergo osteogenic differentiation by incubating in basal medium containing 0.1 μg/ml BMP-2 for 35 days. The expression levels of osteoblastic marker genes were measured by real-time quantitative PCR on day 14. Also assessed was alkaline phosphatase (ALP) activity by a colorimetric kinetic assay and Fast Blue B staining on day 14. Calcium deposition was determined by the calcium assay on day 35.Purpose
Method
Retrospective review. To report the technique and results of vertebral column decancellation (VCD) for the management of sharp angular spinal deformity.Study Design
Objective
We developed a device for the treatment of Ficat and Arlet stage II and III osteonecrosis of the femoral head. This device, which we named the “super-elastic cage,” was designed to provide mechanical support for the necrotic weight-bearing area of the femoral head to prevent its collapse. The cage was used in combination with surgical removal of necrotic bone, insertion of vascularized pedical bone graft, or impacted autologous cancellous bone graft. A total of 93 hips in 62 patients at Ficat stage II to III were included in a 8-year study. Implantations were performed by 2 different approaches: Smith-Peterson approach and minimal invasive approach by the lateral side of great trochanter. The follow-up period was between 72 and 107 months. Of the femoral heads in this study, 82.7% survived. The superelastic cage implantation technique may offer an alternative treatment to the early and middle stages of osteonecrosis of the femoral head.
