Nirong Bao

Comparing Accuracy of Cervical Pedicle Screw Placement between a Guidance System and Manual Manipulation: A Cadaver Study.

Background The aim of this study was to compare the accuracy of cervical pedicle screw placement between a three-dimensional guidance system and manual manipulation. Material/Methods Eighteen adult cadavers were randomized into group A (n=9) and group B (n=9). Ninety pedicle screws were placed into the C3-C7 under the guidance of a three-dimensional locator in group A, and 90 screws were inserted by manual manipulation in group B. The cervical spines were scanned using computed tomography (CT). Parallel and angular offsets of the screws were compared between the two placement methods. Results In group A, 90% of the screws were within the pedicles and 10% breached the pedicle cortex. In group B, 55.6% were within the pedicle and 44.4% breached the pedicle cortex. Locator guidance showed significantly lower parallel and angular offsets in axial CT images (P<0.01), and significantly lower angular offset in sagittal CT images (P<0.01) than manual manipulation. Conclusions Locator guidance is superior to manual manipulation in accuracy of cervical screw placement. Locator guidance might provide better safety than manual manipulation in placing cervical screws.

Autophagy mediated CoCrMo particle-induced peri-implant osteolysis by promoting osteoblast apoptosis

Wear particle-induced osteolysis is the leading cause of aseptic loosening, which is the most common reason for THA (total hip arthroplasty) failure and revision surgery. Although existing studies suggest that osteoblast apoptosis induced by wear debris is involved in aseptic loosening, the underlying mechanism linking wear particles to osteoblast apoptosis remains almost totally unknown. In the present study, we investigated the effect of autophagy on osteoblast apoptosis induced by CoCrMo metal particles (CoPs) in vitro and in a calvarial resorption animal model. Our study demonstrated that CoPs stimulated autophagy in osteoblasts and PIO (particle-induced osteolysis) animal models. Both autophagy inhibitor 3-MA (3-methyladenine) and siRNA of Atg5 could dramatically reduce CoPs-induced apoptosis in osteoblasts. Further, inhibition of autophagy with 3-MA ameliorated the severity of osteolysis in PIO animal models. Moreover, 3-MA also prevented osteoblast apoptosis in an antiautophagic way when tested in PIO model. Collectively, these results suggest that autophagy plays a key role in CoPs-induced osteolysis and that targeting autophagy-related pathways may represent a potential therapeutic approach for treating particle-induced peri-implant osteolysis.

Design of cervical pedicle locator and three-dimensional location of cervical pedicle

Study Design. To develop a high-accuracy, easy-manipulated, and low-cost cervical pedicle three-dimensional locator for guiding cervical pedicle screw placement. Objectives. To improve the safety of cervical pedicle screw insertion, simplify its manipulation, and offer safety guarantees in clinical application. Summary of Background Data. Because of the complicacy of the anatomic structure of cervical pedicle, clinical application of cervical pedicle screw remained hard to popularize. And recent advances on cervical pedicle location did not simplify the manipulation of procedure significantly. Without aid of locator, distance and angle errors were difficult to control. So far, the only instrument for the location of pedicle “computer-assisted image-guided surgical system” is too expensive for clinical use. Furthermore, it has not yet been documented on location instrument for insertion of cervical pedicle screws. Methods. The high-accuracy three-dimensional locator, made of stainless steel was designed to aid cervical pedicle nail placement. The cadavers were inserted nails under guidance of the locator that has been input the corresponding parameters collected from CT images. Results were evaluated by CT scans. Results. A total of 90 nails were inserted into cervical pedicles, 90% of which were found right in the pedicles; 10% had pedicle cortex breaches. Parallel offset error of the locator in cross-sectional and lateral CT image that was 0.56 ± 0.70 and 1.04 ± 0.99; angular offset error was 1.69 ± 2.41 and 6.54 ± 7.08. Conclusion. Three-dimensional locator of cervical pedicle and its localization technique achieved good results for individuated screws insertion into cervical pedicles, having such advantages as easy manipulation, high accuracy, and low cost. The system presented safety guarantee to the application and advanced the prevalence of pedicle techniques. Its principium and design were demonstrated feasible.

SIRT1 protects osteoblasts against particle-induced inflammatory responses and apoptosis in aseptic prosthesis loosening

We hypothesized that SIRT1 downregulation in osteoblasts induced by wear particles was one of the reasons for particle-induced osteolysis (PIO) in total joint arthroplasty failure. In the present study, the expression of SIRT1 was examined in osteoblasts treated with TiAl6V4 particles (TiPs) and CoCrMo particles (CoPs) from materials used in prosthetics and specimens from PIO animal models. To address whether SIRT1 downregulation triggers inflammatory responses and apoptosis in osteoblasts, the effect of a SIRT1 activator, resveratrol on the expression of inflammatory cytokines and apoptosis in particle-treated osteoblasts was tested. The results demonstrated that SIRT1 expression was significantly downregulated in particle-treated osteoblasts and PIO animal models. Both pharmacological activation and overexpression of SIRT1 dramatically reduced the particle-induced expression of inflammatory cytokines and osteoblast apoptosis through NF-κB and p53 signaling, respectively. Furthermore, in PIO animal models, resveratrol significantly reduced the severity of osteolysis. Collectively, the results of the present study indicated that SIRT1 plays a vital role in the pathogenesis of aseptic loosening, and further treatment targeted at SIRT1 possibly lead to novel approaches for prevention of aseptic prosthesis loosening. STATEMENT OF SIGNIFICANCE Aseptic loosening is the most common cause of total hip arthroplasty (THA) and total knee arthroplasty (TKA) failure and revision surgery. However, there is still no effective therapeutic target in the clinical treatment. Besides, the underlying mechanism of aseptic loosening is largely unknown. The result of our study indicated that SIRT1 has the ability to effectively regulate the wear particle-induced inflammatory responses, apoptosis, osteolysis in particle-stimulated osteoblasts and particle-induced osteolysis animal models. Our study provides a potential target for the prevention and treatment of aseptic loosening and further investigated the underlying mechanism of aseptic loosening, which may make contribution to decrease the incidence of THA and TKA failure in the clinical practice.

Free fatty acids are responsible for the hidden blood loss in total hip and knee arthroplasty

Hidden blood loss (HBL), commonly seen post total knee or hip arthroplasty, causes postoperative anemia even after reinfusion or blood transfusion based on the visible blood loss volume. The mechanism of HBL remains unclear although more than one theory had tried to explain it. Free fatty acids, metabolites of fatty emboli that are generated during TKA, THA and other surgery manipulating the medullary canal of femur, had been demonstrated to stimulate the neutrophils in producing reactive oxygen species such (ROS) as hydrogen peroxide and chlorous peroxide. Erythrocytes injury was also shown in parasitic infection, chronic renal disease and paroxysmal nocturnal hemoglobinuria in a mechanism of oxidation of membrane polyunsaturated fatty acids and cytosolic hemoglobin by ROS. Based on these results we hypothesize that free fatty acids generated from fatty emboli in blood circulation are responsible for the hidden blood loss through peroxidating injury of membrane molecules of RBC and hemoglobin. Antioxidants administered intra- or post-operatively are predicted to play a protective role in erythrocytes oxidation and potentially reduce the volume of hidden blood loss after arthroplasty.

ER Stress Mediates TiAl6V4 Particle-Induced Peri-Implant Osteolysis by Promoting RANKL Expression in Fibroblasts.

Wear particle-induced osteolysis is a major cause of aseptic loosening, which is one of the most common reasons for total hip arthroplasty (THA) failure. Previous studies have shown that the synovial fibroblasts present in the periprosthetic membrane are important targets of wear debris during osteolysis. However, the interaction mechanisms between the wear debris and fibroblasts remain largely unknown. In the present study, we investigated the effect of ER (endoplasmic reticulum) stress induced by TiAl6V4 particles (TiPs) in human synovial fibroblasts and calvarial resorption animal models. The expression of ER stress markers, including IRE1-α, GRP78/Bip and CHOP, were determined by western blot in fibroblasts that had been treated with TiPs for various times and concentration. To address whether ER stress was involved in the expression of RANKL, the effects of ER stress blockers (including 4-PBA and TUDCA) on the expression of RANKL in TiPs-treated fibroblasts were examined by real-time PCR, western blot and ELISA. Osteoclastogenesis was assessed by tartrate resistant acid phosphatase (TRAP) staining. Our study demonstrated that ER stress markers were markedly upregulated in TiPs-treated fibroblasts. Blocking ER stress significantly reduced the TiPs-induced expression of RANKL both in vitro and in vivo. Moreover, the inhibition of ER stress ameliorated wear particle-induced osteolysis in animal models. Taken together, these results suggested that the expression of RANKL induced by TiPs was mediated by ER stress in fibroblasts. Therefore, down regulating the ER stress of fibroblasts represents a potential therapeutic approach for wear particle-induced periprosthetic osteolysis.

Probiotics protect mice from CoCrMo particles-induced osteolysis

Wear particle-induced inflammatory osteolysis is the primary cause of aseptic loosening, which is the most common reason for total hip arthroplasty (THA) failure in the med- and long term. Recent studies have suggested an important role of gut microbiota (GM) in modulating the host metabolism and immune system, leading to alterations in bone mass. Probiotic bacteria administered in adequate amounts can alter the composition of GM and confer health benefits to the host. Given the inflammatory osteolysis that occurs in wear debris-induced prosthesis loosening, we examined whether the probiotic Lactobacillus casei could reduce osteolysis in a mouse calvarial resorption model. In this study, L. casei markedly protected mice from CoCrMo particles (CoPs)-induced osteolysis. Osteoclast gene markers and the number of osteoclasts were significantly decreased in L. casei-treated mice. Probiotic treatment decreased the M1-like macrophage phenotype indicated by downregulation of tumor necrosis factor α (TNF-α), interleukin (IL)-6 and inducible nitric oxide synthase (iNOS) and increased the M2-like macrophage phenotype indicated by upregulation of IL-4, IL-10 and arginase. Collectively, these results indicated that the L. casei treatment modulated the immune status and suppressed wear particle-induced osteolysis in vivo. Thus, probiotic treatment may represent a potential preventive and therapeutic approach to reduced wear debris-induced osteolysis.

Proanthocyanidins Attenuation of H2O2-Induced Oxidative Damage in Tendon-Derived Stem Cells via Upregulating Nrf-2 Signaling Pathway

Proanthocyanidins (PCs) have shown inhibition of oxidative damage by improving Nrf-2 expression in many tissues. However, the cytoprotective effects of PCs on H2O2-induced tendon damage have not been verified. The current study was aimed at assessing the cytoprotection of PCs on the oxidative cellular toxicity of tendon-derived stem cells (TDSCs) induced by H2O2. The TDSCs were isolated from patellar tendons of Sprague Dawley (SD) rats, and the cells after third passage were used for subsequent experiments. The isolated cells were identified by flow cytometry assay and multidifferentiation potential assay. Cell Counting Kit-8 assay was performed to examine cell viability. Real-Time PCR and Western Blot were employed to, respectively, assess the mRNA and protein expressions of Nrf-2, GCLM, NQO-1, and HO-1. PCs significantly improved the cell viability of TDSCs. Furthermore, H2O2 upregulated Nrf-2, GCLM, NQO-1, and HO-1 without significant difference, while the proteins expressions were increased with significant difference in PCs group and PCs + H2O2 cotreated group. All the findings indicated that PCs could protect against the oxidative damage induced by H2O2 in TDSCs, and the cytoprotective effects might be due to the ability of PCs to activate the expressions of GCLM, HO-1, and NQO-1 via upregulating Nrf-2 signaling pathway.

Hydrogen treatment reduces tendon adhesion and inflammatory response: MENG et al.

A rat model of tendon repair was established to investigate the effects of hydrogen water on tendon adhesion reduction. Thirty‐six Sprague Dawley rats were randomly divided into a normal saline (NS) group and a hydrogen water (HS) group according to the processing reagents after a tendon repairing operation. Pre‐ and postoperative superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) in subjects’ serum were observed. Skin fibroblasts were grouped into an NS group, H2O2 group, H2 group, and H2O2 H2 group. Expressions of Nrf2, CATA, and γ‐GCS were also tested by Western blot analysis. 8‐OHdG, GSH, MDA, and SOD of the cells were analyzed by the enzyme‐linked immunosorbent assay method. The postoperative SOD activity and GSH contents were significantly reduced (P < 0.05), whereas the postoperative MDA level was significantly increased (P < 0.05). Similarly, the postoperative HS group showed significantly higher SOD activity and GSH contents (P < 0.05) but lower MDA (P < 0.05) compared with the postoperative NS group. MDA and 8‐OHdG were significantly decreased in hydrogen‐rich medium, while SOD and GSH were increased. The expression of Nrf2, CATA, and γ‐GCS in antioxidant system were reduced after H2O2 processing, which were restored after the application of hydrogen‐rich medium. Hydrogen water can reduce tendon adhesion after tendon repairing and prohibit excessive inflammatory response, which could be associated with the activation of the Nrf2 pathway.

miR-338-5p Regulates the Viability, Proliferation, Apoptosis and Migration of Rheumatoid Arthritis Fibroblast-Like Synoviocytes by Targeting NFAT5

Background/Aims: MicroRNAs (miRNAs) have been reported to be involved in Rheumatoid arthritis (RA) pathogenesis and prognosis. However, little is known about the disease mechanism in RA. Here, we aim to investigate the potential association between miR-338-5p and NFAT5 in RA. Methods: Aberrant expression of miR-338-5p in RA tissues and rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) compared to the normal were determined by RT-qPCR. Cell viability was determined using the CCK-8 assay, and cell apoptosis was analyzed via Annexin V-FITC/PI double staining and was detected using flow cytometry. The targeted relationship was determined by TargetScan database and dual luciferase reporter gene assay. Results: Upregulation of miR-338-5p facilitated the proliferation, migration, invasion and induced G0/G1 arrest of RAFLSs while miR-338-5p inhibitor functioned oppositely. Nuclear factor of activated T-cells 5 (NFAT5) was confirmed as a downstream target of miR-338-5p which expression was directly suppressed by miR-338-5p. Overexpression of NFAT5 attenuated the proliferation and metastasis of RAFLSs and those changes could be rescued by co-transfection of miR-338-5p. Conclusion: miR-338-5p promotes RAFLS’s viability and proliferation, migration by targeting NFAT5, suggesting a novel therapeutic strategy for RA.