Surgical outcomes of robotic-assisted percutaneous fixation for thoracolumbar fractures in patients with ankylosing spondylitis.

BACKGROUND: Spinal fractures in patients with ankylosing spondylitis (AS) mainly present as instability, involving all three columns of the spine, and surgical intervention is often considered necessary. However, in AS patients, the significant alterations in bony structure and anatomy result in a lack of identifiable landmarks, which increases the difficulty of pedicle screw implantation. Therefore, we present the clinical outcomes of robotic-assisted percutaneous fixation for thoracolumbar fractures in patients with AS. METHODS: A retrospective review was conducted on a series of 12 patients diagnosed with AS. All patients sustained thoracolumbar fractures between October 2018 and October 2022 and underwent posterior robotic-assisted percutaneous fixation procedures. Outcomes of interest included operative time, intra-operative blood loss, complications, duration of hospital stay and fracture union. The clinical outcomes were assessed using the visual analogue scale (VAS) and Oswestry Disability Index (ODI). To investigate the achieved operative correction, pre- and postoperative radiographs in the lateral plane were analyzed by measuring the Cobb angle. RESULTS: The 12 patients had a mean age of 62.8 ± 13.0 years and a mean follow-up duration of 32.7 ± 18.9 months. Mean hospital stay duration was 15 ± 8.0 days. The mean operative time was 119.6 ± 32.2 min, and the median blood loss was 50 (50, 250) ml. The VAS value improved from 6.8 ± 0.9 preoperatively to 1.3 ± 1.0 at the final follow-up (P < 0.05). The ODI value improved from 83.6 ± 6.1% preoperatively to 11.8 ± 6.6% at the latest follow-up (P < 0.05). The average Cobb angle changed from 15.2 ± 11.0 pre-operatively to 8.3 ± 7.1 at final follow-up (P < 0.05). Bone healing was consistently achieved, with an average healing time of 6 (5.3, 7.0) months. Of the 108 screws implanted, 2 (1.9%) were improperly positioned. One patient experienced delayed nerve injury after the operation, but the nerve function returned to normal upon discharge. CONCLUSION: Posterior robotic-assisted percutaneous internal fixation can be used as an ideal surgical treatment for thoracolumbar fractures in AS patients. However, while robot-assisted pedicle screw placement can enhance the accuracy of pedicle screw insertion, it should not be relied upon solely.

Initial experience of 3-dimensional exoscope in decompression of massive lumbar disc herniation.

OBJECTIVES: To investigate the effect of a three-dimensional (3D) exoscope for decompression of single-segment massive lumbar disc herniation (LDH). METHODS: The study included 56 consecutive patients with single segment massive LDH who underwent decompression assisted by a 3D exoscope from October 2019 to October 2022 at a university hospital. The analysis was based on comparison of perioperative metrics including decompression time, estimated blood loss (EBL) during decompression and postoperative length of stay (PLS); clinical outcomes including assessment using the visual analogue scale (VAS) and the Oswestry disability index (ODI); and incidence of reoperation and complications. RESULTS: The mean decompression time was 28.35 ± 8.93 min (lumbar interbody fusion (LIF)) and 15.50 ± 5.84 min (fenestration discectomy (LOVE surgery)), the mean EBL during decompression was 42.65 ± 12.42 ml (LIF) and 24.32 ± 8.61 ml (LOVE surgery), and the mean PLS was 4.56 ± 0.82 days (LIF) and 2.00 ± 0.65 days (LOVE surgery). There were no complications such as cerebrospinal fluid leakage, nerve root injury and epidural hematoma. All patients who underwent decompression assisted by a 3D exoscope were followed up for 6 months. At the last follow-up, the VAS and ODI scores were significantly improved from the preoperative period to the last follow-up (P < 0.05). CONCLUSIONS: A 3D exoscope provides a visually detailed, deep and clear surgical field, which makes decompression safer and more effective and reduces short-term complications. A 3D exoscope may be a good assistance tool during decompression for single-segment massive LDH.

Mechanical Loading Improves Tendon-Bone Healing in a Rabbit Anterior Cruciate Ligament Reconstruction Model by Promoting Proliferation and Matrix Formation of Mesenchymal Stem Cells and Tendon Cells.

BACKGROUND/AIMS: This study investigated the effect of mechanical stress on tendon-bone healing in a rabbit anterior cruciate ligament (ACL) reconstruction model as well as cell proliferation and matrix formation in co-culture of bone-marrow mesenchymal stem cells (BMSCs) and tendon cells (TCs). METHODS: The effect of continuous passive motion (CPM) therapy on tendon-bone healing in a rabbit ACL reconstruction model was evaluated by histological analysis, biomechanical testing and gene expressions at the tendon-bone interface. Furthermore, the effect of mechanical stretch on cell proliferation and matrix synthesis in BMSC/TC co-culture was also examined. RESULTS: Postoperative CPM therapy significantly enhanced tendon-bone healing, as evidenced by increased amount of fibrocartilage, elevated ultimate load to failure levels, and up-regulated gene expressions of Collagen I, alkaline phosphatase, osteopontin, Tenascin C and tenomodulin at the tendon-bone junction. In addition, BMSC/TC co-culture treated with mechanical stretch showed a higher rate of cell proliferation and enhanced expressions of Collagen I, Collagen III, alkaline phosphatase, osteopontin, Tenascin C and tenomodulin than that of controls. CONCLUSION: These results demonstrated that proliferation and differentiation of local precursor cells could be enhanced by mechanical stimulation, which results in enhanced regenerative potential of BMSCs and TCs in tendon-bone healing.

Activation of α7 nicotinic acetylcholine receptors prevents monosodium iodoacetate-induced osteoarthritis in rats.

BACKGROUND/AIMS: Although some evidence suggests that the prevalence of osteoarthritis (OA) is lower in smokers compared to nonsmokers, the mechanisms of nicotine-induced protection remain unclear. Stimulation of the α7 nicotinic acetylcholine receptor (α7-nAChR) appears to be a critical mechanism underlying the anti-inflammatory potential of cholinergic agonists in immune cells. The inhibition of secreted inflammatory molecules and the subsequent inflammatory processes have been proposed as a novel strategy for the treatment of OA. The objective of the present study was to determine whether nicotine-induced protection in a monosodium iodoacetate (MIA) rat model of OA occurs via α7-nAChR-mediated inhibition of chondrocytes. METHODS: Both in vivo (MIA) and in vitro (MIA; Interleukin-1ß, IL-1ß) models of OA were used to investigate the roles and the possible mechanisms whereby α7-nAChRs protect against knee joint degradation. Multiple experimental approaches, including macroscopic, histological analysis, chondrocyte cell cultures, confocal microscopy, and western blotting, were employed to elucidate the mechanisms of α7-nAChR-mediated protection. RESULTS: Systemic administration of nicotine alleviated MIA-induced joint degradation. The protective effects of nicotine were abolished by administration of the α7-nAChR-selective antagonist methyllycaconitine (MLA). In primary cultured rat chondrocytes, pretreatment with nicotine suppressed both p38, extracellular regulated kinase (Erk) 1/2 and c-Jun-N-terminal kinase (JNK) mitogen-activated protein kinases (MAPK) phosphorylation and phosphorylated nuclear factor-kappa B (NF-κB) p65 activation induced by MIA- or IL-1ß, and these effects were also reversed by MLA. CONCLUSION: Taken together, our results suggest that activation α7-nAChRs is an important mechanism underlying the protective effects of nicotine.

Association between cytotoxic T lymphocyte antigen-4 +49A/G, -1722T/C, and -1661A/G polymorphisms and cancer risk: a meta-analysis.

Cytotoxic T lymphocyte antigen-4 (CTLA-4), a key gene that contributes to the susceptibility and clinical course of cancer, is an important down-regulator of T cell activation and proliferation. The +49A/G polymorphism is commonly studied because of its association with cancer risks. However, other polymorphisms, such as -1722T/C and -1661A/G, have not been studied in detail. We performed a meta-analysis using 43 eligible case-control studies with a total of 19,089 patients and 21,388 controls to examine the association between CTLA-4 +49A/G, -1722T/C, and -1661A/G polymorphisms and cancer risk. We searched the PubMed and EMBASE databases for all articles published up to July 17, 2013. Individuals with the +49 A allele (AA/AG vs. GG, odds ratio (OR) = 1.21, 95% confidence interval (95% CI) = 1.16-1.27) and -1661 G allele (AG/GG vs. AA, OR = 1.52, 95% CI = 1.34-1.73) had increased cancer risk. However, no significant association between cancer risk and the -1722T/C polymorphism was found (CC/CT vs. TT, OR = 1.04, 95% CI = 0.92-1.16). In subgroup analysis for the +49A/G polymorphism, increased cancer risk remained in the subgroups of Asians (OR = 1.25, 95 % CI = 1.18-1.31), patients with breast cancer (OR = 1.28, 95% CI = 1.15-1.42), and patients with lung cancer (OR = 1.20, 95 % CI = 1.07-1.35). For the -1661A/G polymorphism, increased cancer risk remained in the subgroups of Asians (OR = 1.52, 95% CI = 1.34-1.73), patients with breast cancer (OR = 1.48, 95% CI = 1.07-2.03), and patients with oral cancer (OR = 3.16, 95% CI = 1.84-5.45). However, no significant increase in cancer risk was found in the subgroups for the -1722T/C polymorphism. In conclusion, the results suggest that +49A/G and -1661A/G polymorphisms in CTLA-4 are risk factors for cancers, whereas the -1722T/C polymorphism is not associated with an increased risk of cancer.

Reproductive toxicity in adult male rats following intra-articular injection of cobalt-chromium nanoparticles.

BACKGROUND: Recent studies have reported that metallic nanoparticles and ions from cobalt-chromium (CoCr) alloy prostheses had potential adverse effects. However, the biological effects of CoCr nanoparticles on male reproductive function remain unclear. The objective of this study is to investigate the reproductive toxicity in adult male rats following intra-articular injection of cobalt-chromium nanoparticles. METHODS: CoCr nanoparticles were generated by a spark discharge method. Adult male rats received intra-articular injections of CoCr nanoparticles once a week at a low (20 µg/kg b.w.), medium (100 µg/kg b.w.) or high dose (500 µg/kg b.w.) for 10 consecutive weeks. The control group received intra-articular injections of physiological saline. After the final injection, all rats were held for a 7-day post-exposure period. The effects on male reproductive function were observed, including the coefficient of testicular to body weight, the epididymal sperm parameters, the concentration of metal ions in serum and testis, the activity of antioxidase and the content of lipid peroxide in the testis, and histopathological examination. RESULTS: Compared with the control group, intra-articular injection of high dose CoCr nanoparticles could significantly reduce epididymal sperm motility, viability and concentration, increase abnormal sperm rate and levels of Co and Cr ions in serum and in the testis, and induce testicular damage and pathological changes via oxidative stress. CONCLUSIONS: Intra-articular injection of high dose CoCr nanoparticles from MOM articulation may have potential reproductive toxicity in adult male rats.

Periodic Mechanical Stress Inhibits the Development of Osteoarthritis via Regulating ATF3-Akt Axis.

Purpose: The development of osteoarthritis (OA) has been linked to mechanical factors. Studies suggest that periodic mechanical stress (PMS) may be a factor contributing to cartilage repair and the onset of OA. Therefore, this study was designed to explore the effects and underlying mechanisms of PMS on OA development. Patients and Methods: Firstly, surgery and interleukin (IL)-1ß were used for the establishment of rat/cell models of OA, respectively. Subsequently, activating transcription factor (ATF) 3 expression was knocked down in OA rats, and OA chondrocytes were treated with different heights (0, 1, 2, 4, 8 cm) of PMS or si-ATF. Safranin O staining was used to observe the histological changes in the rat knee joint, and enzyme-linked immunosorbent assay (ELISA) was performed to detect levels of tumor necrosis factor (TNF)-α, IL-6, and IL-8 in vivo and in vitro. Further, the expression of extracellular matrix (ECM) proteins in the rat knee joint was assessed immunohistochemistry. Flow cytometry was used to evaluate chondrocyte apoptosis. Lastly, Western blot was performed to detect the expression of related proteins of the protein kinase B (Akt) signaling pathway and ECM. Results: The OA rat model was successfully constructed. Further experiments indicated that the knockdown of ATF3 not only alleviated joint swelling, pain, inflammatory response and pathological damage, but also promoted ECM synthesis and the phosphorylation of Akt in OA rats. In vitro experiments showed that PMS (4 cm) effectively inhibited cell apoptosis, decreased the levels of TNF-α, IL-6 and IL-8, promoted ECM synthesis, and activated the Akt signaling pathway in osteoarthritic chondrocytes. However, ATF3 overexpression reversed the positive effects of PMS on osteoarthritic chondrocytes. Conclusion: PMS can effectively inhibit the development of OA, and its protective effects may be attributed to the down-regulation of ATF3 expression and activation of the Akt signaling pathway.

Integrin αVß3 Signaling in the Progression of Osteoarthritis Induced by Excessive Mechanical Stress.

Osteoarthritis (OA) is believed to be linked with cartilage degeneration, subchondral bone sclerosis, and synovial inflammation that lead to joint failure, and yet treatment that can effectively reverse the pathological process of the disease still not exists. Recent evidence suggests excessive mechanical stress (eMS) as an essential role in the pathogenesis of OA. Increased levels of integrin αVß3 have been detected in osteoarthritic cartilage and were previously implicated in OA pathogenesis. However, the role of integrin αVß3 in the process of eMS-induced OA remains unclear. Here, histologic and proteomic analyses of osteoarthritic cartilage in a rat destabilization of the medial meniscus model demonstrated elevated expression of integrin αVß3 as well as more serious cartilage degeneration in the medial weight-bearing area. Furthermore, results of in vitro study demonstrated that eMS led to a significant increase of integrin αVß3 expression and phosphorylation of downstream signaling molecules such as FAK and ERK, as well as upregulated expressions of inflammatory and degradative mediators. In addition, we found that inhibition of integrin αVß3 could alleviate chondrocyte inflammation triggered by eMS both in vivo and in vitro. Our findings suggest a central role for upregulation of integrin αVß3 signaling in OA pathogenesis and demonstrate that activation of integrin αVß3 signaling in cartilage contributes to inflammation and joint destruction in eMS-induced OA. Taken together, our data presented here provide a possibility for targeting integrin αVß3 signaling pathway as a disease-modifying therapy.

Prognostic and immunological significance of an M1 macrophage-related gene signature in osteosarcoma.

As the most abundant infiltrating immune cells in the tumor microenvironment (TME), tumor-associated macrophages (TAMs) are pivotal in tumor development and treatment. The present investigation endeavors to explore the potential of M1 macrophage-related genes (MRGs) as biomarkers for assessing risk in individuals with osteosarcoma. RNA-sequence data and clinical data were derived from TCGA and GEO databases. The CIBERSORT method was utilized to discern subtypes of tumor-infiltrating immune cells. Identification of MRGs was achieved through Pearson correlation analysis. A prognostic risk model for MRGs was developed using Cox and LASSO regression analyses. A tripartite gene signature comprising CD37, GABRD, and ARHGAP25 was an independent prognostic indicator and was employed to develop a risk score model. The internal and external validation cohort confirmed the results. The area under the ROC curve (AUC) was determined for survival periods of 1 year, three years, and five years, yielding values of 0.746, 0.839, and 0.850, respectively. The C-index of the risk score was found to be superior to clinicopathological factors. GO/KEGG enrichment showed that the differences between high- and low-risk groups were predominantly associated with immune response pathways. Immune-related analysis related to proportions of immune cells, immune function, and expression levels of immune checkpoint genes all showed differences between the high- and low-risk groups. The qRT-PCR and Western blotting results indicate that CD37 expression was markedly higher in MG63 and U2OS cell lines when compared to normal osteoblast hFOB1.19. In U2OS cell line, GABRD expression levels were significantly upregulated. ARHGAP25 expression levels were elevated in both 143B and U2OS cell lines. In summary, utilizing a macrophage genes signature demonstrates efficacy in predicting both the prognosis and therapy response of OS. Additionally, immune analysis confirms a correlation between the risk score and the tumor microenvironment. Our findings, therefore, provide a cogent account for the disparate prognoses observed among patients and furnish a justification for further inquiry into biomarkers and anti-tumor treatment strategies.

Mechanical Stress Regulates Osteogenesis and Adipogenesis of Rat Mesenchymal Stem Cells through PI3K/Akt/GSK-3ß/ß-Catenin Signaling Pathway.

Osteogenesis and adipogenesis of bone marrow mesenchymal stem cells (BMSCs) are regarded as being of great importance in the regulation of bone remodeling. In this study, rat BMSCs were exposed to different levels of cyclic mechanical stress generated by liquid drops and cultured in general medium or adipogenic medium. Markers of osteogenic (Runx2 and Collagen I) and adipogenic (C/EBPα, PPARγ, and lipid droplets) differentiation were detected using Western blot and histological staining. The protein levels of members of the phosphatidylinositol 3-kinase (PI3K)/Akt/glycogen synthase kinase 3ß (GSK-3ß)/ß-catenin signaling pathway were also examined. Results showed that small-magnitude stress significantly upregulated Runx2 and Collagen I and downregulated PPARγ and C/EBPα expression in BMSCs cultured in adipogenic medium, while large-magnitude stress reversed the effect when compared with unloading groups. The PI3K/Akt signaling pathway could be strongly activated by mechanical stimulation; however, large-magnitude stress led to decreased activation of the signaling pathway when compared with small-magnitude stress. Activation of ß-catenin with LiCl led to increased expression of Runx2 and Collagen I and reduction of C/EBPα and PPARγ expression in BMSCs. Inhibition of PI3K/Akt signaling partially blocked the expression of ß-catenin. Taken together, our results indicate that mechanical stress-regulated osteogenesis and adipogenesis of rat BMSCs are mediated, at least in part, by the PI3K/Akt/GSK-3ß/ß-catenin signaling pathway.

TRIM14 regulates cell proliferation and invasion in osteosarcoma via promotion of the AKT signaling pathway.

Recent studies have shown that some members of the tripartite motif-containing protein (TRIM) family serve as important regulators of tumorigenesis. However, the biological role of TRIM14 in osteosarcoma remains to be established. In this study, we showed that TRIM14 is upregulated in human osteosarcoma specimens and cell lines, and correlated with osteosarcoma progression and shorter patient survival times. Functional studies demonstrated that overexpression of TRIM14 enhances osteosarcoma cell proliferation, clone formation, cell cycle procession, migration and invasion in vitro and promotes tumor growth in vivo, and conversely, its silencing has the opposite effects. Furthermore, TRIM14 overexpression induced activation of the AKT pathway. Inhibition of AKT expression reversed the TRIM14-mediated promotory effects on cell growth and mobility, in addition to TRIM14-induced epithelial-to-mesenchymal transition (EMT) and cyclin D1 upregulation. Our findings collectively suggest that TRIM14 functions as an oncogene by upregulating the AKT signaling pathway in osteosarcoma cells, supporting its potential utility as a therapeutic target for this disease.

Cyclic Compressive Stress Regulates Apoptosis in Rat Osteoblasts: Involvement of PI3K/Akt and JNK MAPK Signaling Pathways.

It is widely accepted that physiological mechanical stimulation suppresses apoptosis and induces synthesis of extracellular matrix by osteoblasts; however, the effect of stress overloading on osteoblasts has not been fully illustrated. In the present study, we investigated the effect of cyclic compressive stress on rat osteoblasts apoptosis, using a novel liquid drop method to generate mechanical stress on osteoblast monolayers. After treatment with different levels of mechanical stress, apoptosis of osteoblasts and activations of mitogen-activated protein kinases (MAPKs) and PI3-kinase (PI3K)/Akt signaling pathways were investigated. Osteoblasts apoptosis was observed after treated with specific inhibitors prior to mechanical stimulation. Protein levels of Bax/Bcl-2/caspase-3 signaling were determined using western blot with or without inhibitors of PI3K/Akt and phosphorylation of c-jun N-terminal kinase (JNK) MAPK. Results showed that mechanical stimulation led to osteoblasts apoptosis in a dose-dependent manner and a remarkable activation of MAPKs and PI3K/Akt signaling pathways. Activation of PI3K/Akt protected against apoptosis, whereas JNK MAPK increased apoptosis via regulation of Bax/Bcl-2/caspase-3 activation. In summary, the PI3K/Akt and JNK MAPK signaling pathways played opposing roles in osteoblasts apoptosis, resulting in inhibition of apoptosis upon small-magnitude stress and increased apoptosis upon large-magnitude stress.

Effects of mesenchymal stem cells on interleukin-1ß-treated chondrocytes and cartilage in a rat osteoarthritic model.

In the present study, the effects and mechanisms of mesenchymal stem cells (MSCs) on interleukin (IL)-1ß-stimulated rat chondrocytes, as well as cartilage from a rat model of osteoarthritis (OA) induced by anterior cruciate ligament transection and medial meniscectomy were investigated. Confluent rat chondrocytes were treated with IL-1ß (10 ng/ml), then cultured indirectly with or without MSCs at a ratio of 2:1. Total RNA and protein were collected at various time-points, and western blot and reverse transcription-quantitative polymerase chain reaction analyses were used to investigate the expression of type II collagen (Col2), aggrecan, matrix metalloproteinase-13 (MMP-13) and cyclooxygenase-2 (COX-2). The activation of extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), nuclear factor-κB (NF-κB) p65 and inhibitory-κ-B-α (IκBα) were also assessed by western blotting. In addition, the in vivo effects of MSCs in a rat OA model were assessed by histology and western blot analysis. The results indicated that in vitro, IL-1ß markedly upregulated the expression of MMP-13, COX-2, phosphorylated ERK1/2, JNK, p38 MAPK and NF-κB p65, and inhibited the expression of Col2, aggrecan and IκBα. Conversely, MSCs enhanced the expression of Col2, aggrecan and IκBα, and inhibited the expression of MMP-13 and NF-κB p65 in IL-1ß-stimulated rat chondrocytes. In vivo histological and western blot analyses revealed analogous results to the in vitro findings. The results of the present study demonstrated that MSCs suppressed the inflammatory response and extracellular matrix degradation in IL-1ß­induced rat chondrocytes, as well as cartilage in a osteoarthritic rat model, in part via the NF-κB signaling pathway.

Comparison of the efficacy of bone marrow mononuclear cells and bone mesenchymal stem cells in the treatment of osteoarthritis in a sheep model.

OBJECTIVE: To evaluate the therapeutic efficacy of uncultured bone marrow mononuclear cells (BMMCs) and bone mesenchymal stem cells in an osteoarthritis (OA) model of sheep. METHODS: Induction of sheep OA was performed surgically through anterior cruciate ligament transection and medial meniscectomy. After 12 weeks, concentrated BMMCs obtained from autologous bone marrow harvested from anterior iliac crest or a single dose of 10 million autologous bone mesenchymal stem cells (BMSCs) suspended in phosphate-buffered saline (PBS) was delivered to the injured knee via direct intra-articular injection. Animals of the PBS group received vehicle alone. The contra-lateral joints were selected randomly as the control group. Knees of the four groups were compared macroscopically and histologically, and glycosaminoglycan (GAG) contents normalized to cartilage wet weight were measured at lesions of cartilage from medial condyle of the femur head. Gene expression levels of type II collagen (Col2A1), Aggrecan and matrix metalloproteinase-13 (MMP-13) in cartilage were measured based on RT-PCR and prostaglandin E2 (PGE2), Tumor Necrosis Factor-α (TNF-α) and Transforming Growth Factor beta (TGF-ß) concentrations in synovial fluid were determined with ELISA assays at 8 weeks after injection. RESULTS: At 8 weeks post cell transplantation, partial cartilage repair was observed in the cell therapy, but not the PBS group (P<0.05). The BMSCs group showed higher regeneration of cartilage and lower proteoglycan loss than the BMMCs group (P<0.05). Concentrated BMMCs injection led to a weaker treatment effect, but also inhibited PGE2, TNF-α and TGF-ß levels in synovial fluid and promoted higher levels of Aggrecan and Col2A1 and downregulation of MMP-13 in sheep chondrocytes in a similar manner to BMSCs, compared with the PBS group. CONCLUSIONS: Bone marrow cells showed therapeutic efficacy in a sheep model of OA. Despite similar therapeutic potential, the easier and faster process of collection and isolation of BMMCs supports their utility as an effective alternative for OA treatment in the clinic.