CHMP5 attenuates osteoarthritis via inhibiting chondrocyte apoptosis and extracellular matrix degradation: involvement of NF-κB pathway.

BACKGROUND: Osteoarthritis (OA), the most common joint disease, is linked with chondrocyte apoptosis and extracellular matrix (ECM) degradation. Charged multivesicular body protein 5 (CHMP5), a member of the multivesicular body, has been reported to serve as an anti-apoptotic protein to participate in leukemia development. However, the effects of CHMP5 on apoptosis and ECM degradation in OA remain unclear. METHODS: In this study, quantitative proteomics was performed to analyze differential proteins between normal and OA patient articular cartilages. The OA mouse model was constructed by the destabilization of the medial meniscus (DMM). In vitro, interleukin-1 beta (IL-1ß) was used to induce OA in human chondrocytes. CHMP5 overexpression and silencing vectors were created using an adenovirus system. The effects of CHMP5 on IL-1ß-induced chondrocyte apoptosis were investigated by CCK-8, flow cytometry, and western blot. The effects on ECM degradation were examined by western blot and immunofluorescence. The potential mechanism was explored by western blot and Co-IP assays. RESULTS: Downregulated CHMP5 was identified by proteomics in OA patient cartilages, which was verified in human and mouse articular cartilages. CHMP5 overexpression repressed cell apoptosis and ECM degradation in OA chondrocytes. However, silencing CHMP5 exacerbated OA chondrocyte apoptosis and ECM degradation. Furthermore, we found that the protective effect of CHMP5 against OA was involved in nuclear factor kappa B (NF-κB) signaling pathway. CONCLUSIONS: This study demonstrated that CHMP5 repressed IL-1ß-induced chondrocyte apoptosis and ECM degradation and blocked NF-κB activation. It was shown that CHMP5 might be a novel potential therapeutic target for OA in the future.

MSRB2 Ameliorates H2O2-induced Chondrocyte Oxidative Stress and Suppresses Apoptosis in Osteoarthritis.

BACKGROUND: Chondrocyte oxidative stress and apoptosis are critical factors contributing to the pathogenesis of osteoarthritis (OA). Methionine sulfoxide reductase B2 (MSRB2) is a mitochondrial protein that protects cells from oxidative stress and is involved in apoptosis. This study aimed to investigated the expression of MSRB2 in articular cartilage tissues and elucidated its effect on H2O2-stimulated chondrocytes. METHODS: Human chondrocytes were cultured in Dulbecco's modified Eagle's medium (DMEM)/F12. MSRB2 overexpression in chondrocytes was achieved by transfecting with an MSRB2 overexpression plasmid. Western blot, quantitative RT-PCR, Immunofluorescence staining, and TUNEL assay were employed in this study. RESULTS: MSRB2 expression was found to be reduced in OA patients. Furthermore, overexpression of MSRB2 in H2O2-induced chondrocytes mitigated apoptosis and enhanced cell viability. Elevated MSRB2 expression diminished chondrocyte ROS contents, decreased cytochrome C (Cyc) in the cytoplasm, and regulated mitochondrial membrane potential to maintain mitochondrial homeostasis. Interestingly, knockdown of charged multivesicular body protein 5 (CHMP5) led to a decreased inMSRB2 expression in chondrocytes. Additionally, protein levels of CHMP5 and MSRB2 were reduced in H2O2-stimulated chondrocytes, and silencing CHMP5 reduced MSRB2 expression. Knockdown of CHMP5 increased cleaved caspase-3 expression in H2O2-induced chondrocytes and elevated TUNEL-positive chondrocytes. CONCLUSION: MSRB2 decreased in OA, and overexpression of MSRB2 alleviated oxidative stress and apoptosis of chondrocyte.

BASP1 knockdown suppresses chondrocyte apoptosis and extracellular matrix degradation in vivo and in vitro: A possible therapeutic approach for osteoarthritis.

Osteoarthritis(OA) is an age-related degenerative disease involving chondrocyte apoptosis and extracellular matrix(ECM) degradation.Brain acid soluble protein 1(BASP1) has been reported to induce apoptosis.Thus, we speculated that BASP1 might regulate OA progression by inducing apoptosis, which is also the purpose of this study.The cartilage of the knee joint was collected from OA patients who received the joint replacement.In OA cartilage tissue,we found BASP1 expression was highly expressed, which inferred that BASP1 might be involved in OA.To validate our hypothesis, destabilization of the medial meniscus (DMM) surgery-induced male C57BL/6mice and interleukin-1ß (IL-1ß)-treated human chondrocytes were used to mimic the OA environment.BASP1 knockdown in mice and chondrocytes was achieved by adenovirus carried with BASP1-specific shRNA.High expression of BASP1 was observed in OA mice, which was also verified in IL-1ß-treated chondrocytes.The potential mechanism of BASP1 in OA was further explored in vitro.BASP1 knockdown alleviated IL-1ß-induced apoptosis and ECM degradation, as reflected by the decreased number of apoptotic cells and matrix metalloproteases 13 expression,and the increased collagen II expression.Our findings indicated that BASP1 knockdown alleviated OA progression by inhibiting apoptosis and ECM degradation, suggesting that inhibiting BASP1 may be a potentially applicable method for preventing OA.

Erythropoietin alleviates astrocyte pyroptosis by targeting the miR-325-3p/Gsdmd axis in rat spinal cord injury.

BACKGROUND: Neuroinflammation plays an important role in spinal cord injury (SCI), and an increasing number of studies have focused on the role of astrocytes in neuroinflammation. Pyroptosis is an inflammation-related form of programmed cell death, and neuroinflammation induced by astrocytes in the form of pyroptosis has been widely reported in many central nervous system diseases. Recent studies have found that erythropoietin has significant anti-inflammatory and neuroprotective effects in SCI; however, it has not been reported whether erythropoietin can reduce neuroinflammation by inhibiting neural cell pyroptosis in SCI. METHODS: A GEO dataset (GSE153720) was used to analyse the expression of pyroptosis-related genes in sham astrocytes and astrocytes 7 days, 1 month and 3 months after SCI. TargetScan and miRDB databases were used to predict the miRNA that could bind to the 3'UTR of rat Gsdmd. Primary rat spinal astrocytes were used for in vitro experiments, and the modified version of Allen's method was used to establish the rat SCI model. Western blotting, quantitative real-time polymerase chain reaction, flow cytometry, immunofluorescence, lactate dehydrogenase release assay and propidium iodide staining were used to detect the pyroptosis phenotype. A dual luciferase reporter gene assay was used to verify that miR-325-3p can bind to the 3'UTR of Gsdmd. RESULTS: We found that pyroptosis-related genes mediated by the canonical NLRP3 inflammasome were highly expressed in astrocytes in an SCI animal model by bioinformatic analysis. We also observed that erythropoietin could reduce astrocyte pyroptosis in vivo and in vitro. In addition, we predicted miRNAs that regulate Gsdmd, the pyroptosis executor, and verified that erythropoietin inhibits astrocyte pyroptosis in SCI through the miR-325-3p/Gsdmd axis. CONCLUSIONS: We demonstrated that erythropoietin can inhibit astrocyte pyroptosis through the miR-325-3p/Gsdmd axis. This study is expected to provide a new mechanism for erythropoietin in the treatment of SCI and a more reliable theoretical basis for clinical research.

From cells to organs: progress and potential in cartilaginous organoids research.

While cartilage tissue engineering has significantly improved the speed and quality of cartilage regeneration, the underlying metabolic mechanisms are complex, making research in this area lengthy and challenging. In the past decade, organoids have evolved rapidly as valuable research tools. Methods to create these advanced human cell models range from simple tissue culture techniques to complex bioengineering approaches. Cartilaginous organoids in part mimic the microphysiology of human cartilage and fill a gap in high-fidelity cartilage disease models to a certain extent. They hold great promise to elucidate the pathogenic mechanism of a diversity of cartilage diseases and prove crucial in the development of new drugs. This review will focus on the research progress of cartilaginous organoids and propose strategies for cartilaginous organoid construction, study directions, and future perspectives.

SNIP1 reduces extracellular matrix degradation and inflammation via inhibiting the NF-κB signaling pathway in osteoarthritis.

Osteoarthritis (OA), the most common joint disease, is characterized by inflammation and cartilage degradation. Previous studies illustrated that Smad nuclear-interacting protein 1 (SNIP1) is an inhibitor of the TGF-ß signal transduction pathway and SNIP1 has been reported as an anti-inflammatory factor. This study aimed to explore the role of SNIP1 in OA progression. In this study, the SNIP1 expression was evaluated in OA human and OA mice tissue and interleukin-1 beta (IL-1ß)-induced chondrocytes. The Safranin-O (SO) staining and osteoarthritis research society international (OARSI) scoring system was used to evaluate cartilage injury. The gain- and loss-of-function studies for SNIP1 were performed in chondrocytes. The SNIP1 overexpression adenovirus was injected into mice by intra-articular injection. The SNIP1 expression was decreased in OA patients, OA mice, and IL-1ß-stimulated chondrocytes. The cartilage injury of medial meniscus-induced OA (DMM-OA) mice at 8 weeks showed more severe than that at 4 weeks. The expression of SNIP1 was lower at 8 weeks than that at 4 weeks. In IL-1ß-stimulated chondrocytes, SNIP1 overexpression reduced the expression of TNF-α and IL-6, alleviated ECM degradation, reduced the phosphorylation levels of p65 and IκBα, and decreased the p65 level in nuclear. Moreover, overexpression of SNIP1 alleviated cartilage injury in DMM-OA mice. In brief, our study suggested that SNIP1 alleviated OA and repressed inflammation by inhibiting the activation of NF-κB. This study might provide a new insight into OA treatment.

Identification of the CCL2 PI3K/Akt axis involved in autophagy and apoptosis after spinal cord injury.

Spinal cord injury (SCI) is a devastating neurological disease with no cure that usually results in irreversible loss of sensory and voluntary motor functions below the injury site. We conducted an in-depth bioinformatics analysis combining the gene expression omnibus spinal cord injury database and the autophagy database and found that the expression of the autophagy gene CCL2 was significantly upregulated and the PI3K/Akt/mTOR signaling pathway was activated after SCI. The results of the bioinformatics analysis were verified by constructing animal and cellular models of SCI. We then used small interfering RNA to inhibit the expression of CCL2 and PI3K to inhibit and activate the PI3K/Akt/mTOR signaling pathway; western blot, immunofluorescence, monodansylcadaverine, and cell flow techniques were used to detect the expression of key proteins involved in downstream autophagy and apoptosis. We found that when PI3K inhibitors were activated, apoptosis decreased, the levels of autophagy-positive proteins LC3-I/LC3-II and Bcl-1 increased, the levels of autophagy-negative protein P62 decreased, the levels of pro-apoptotic proteins Bax and caspase-3 decreased, the levels of the apoptosis-inhibiting protein Bcl-2 increased. In contrast, when a PI3K activator was used, autophagy was inhibited, and apoptosis was increased. This study revealed the effect of CCL2 on autophagy and apoptosis after SCI through the PI3K/Akt/mTOR signaling pathway. By blocking the expression of the autophagy-related gene CCL2, the autophagic protective response can be activated, and apoptosis can be inhibited, which may be a promising strategy for the treatment of SCI.

Circ-Ctnnb1 Regulates Neuronal Injury in Spinal Cord Injury through the Wnt/ß-Catenin Signaling Pathway.

STUDY DESIGN: Spinal cord injury (SCI) rat model and cell model were established for in vivo and in vitro experiments. Functional assays were utilized to explore the role of the circRNAs derived from catenin beta 1 (mmu_circ_0001859, circ-Ctnnb1 herein) in regulating neuronal cell viability and apoptosis. Bioinformatics analysis and mechanism experiments were conducted to assess the underlying molecular mechanism of circ-Ctnnb1. OBJECTIVE: We aimed to probe into the biological function of circ-Ctnnb1 in neuronal cells of SCI. METHODS: The rat model of SCI and hypoxia-induced cell model were constructed to examine circ-Ctnnb1 expression in SCI through quantitative reverse transcription real-time polymerase chain reaction. The Basso, Beattie, and Bresnahan score was utilized for evaluating the neurological function. Terminal-deoxynucleotidyl transferase mediated nick end labeling assays were performed to assess the apoptosis of neuronal cells. RNase R and actinomycin D were used to treat cells to evaluate the stability of circ-Ctnnb1. RESULTS: Circ-Ctnnb1 was highly expressed in SCI rat models and hypoxia-induced neuronal cells, and its deletion elevated the apoptosis rate of hypoxia-induced neuronal cells. Furthermore, circ-Ctnnb1 activated the Wnt/ß-catenin signaling pathway via sponging mircoRNA-205-5p (miR-205-5p) to upregulate Ctnnb1 and Wnt family member 2B (Wnt2b). CONCLUSION: Circ-Ctnnb1 promotes SCI through regulating Wnt/ß-catenin signaling via modulating the miR-205-5p/Ctnnb1/Wnt2b axis.

hsa_circ_0058122 knockdown prevents steroid-induced osteonecrosis of the femoral head by inhibiting human umbilical vein endothelial cells apoptosis via the miR-7974/IGFBP5 axis.

BACKGROUND: Steroid-induced osteonecrosis of femoral head (SONFH) is a serious complication of glucocorticoid overused. Recent evidence has demonstrated that circRNAs exert key pathophysiological roles in a variety of disease processes. However, the role of circRNA in SONFH remains largely unknown. The current study sought to evaluate how hsa_circ_0058122 affects SONFH in dexamethasone (DEX) treated human umbilical vein endothelial cells (HUVECs) model. METHODS: RT-PCR was used to demonstrate the hsa_circ_0058122 expression level in Dex-treated HUVECs cells. The effects of hsa_circ_0058122 on HUVECs apoptosis were evaluated via overexpression plasmid and siRNA. Using dual-luciferase and fluorescence in situ hybridization assays, we demonstrated that hsa_circ_0058122 binds to miR-7974 thereby facilitating HUVECs apoptosis. Bioinformatics analysis and western blot were performed to confirm target genes of hsa-miR-7974. RESULTS: In our previous work, we revealed the top 20 elevated circRNAs in SONFH patients were hsa_circ_0010027, hsa_circ_0058115, hsa_circ_0010026, hsa_circ_0058839, hsa_circ_0056886, hsa_circ_0056885, hsa_circ_0058146, hsa_circ_0058105, hsa_circ_0058112, hsa_circ_0058143, hsa_circ_0058102, hsa_circ_0058090, hsa_circ_0075353, hsa_circ_0058126, hsa_circ_0058130, hsa_circ_0058140, hsa_circ_0058122, hsa_circ_0058123, hsa_circ_0058103, and hsa_circ_0058121. Among these, hsa_circ_0058122 was finally selected for further investigation. We found hsa_circ_0058122 expression was markedly elevated in Dex-treated HUVECs cells, and the Dex-mediated HUVEC apoptosis was impaired in hsa_circ_0058122-silenced cells and increased in hsa_circ_0058122-overexpressing cells. hsa_circ_0058122 competitively binds to hsa-miR-7974, which in turn interacts with insulin-like growth factor binding protein 5 (IGFBP5). CONCLUSIONS: hsa_circ_0058122/miR-7974/IGFBP5 was proposed to be a key regulatory pathway for SONFH. DEX treatment upregulated hsa_circ_0058122 expression in HUVECs, which sponged miR-7974, thereby increasing IGFBP5 expression, the hsa_circ_0058122/miR-7974/IGFBP5 axis contributed to the Dex-mediated apoptosis. These findings may identify novel targets for SONFH molecular therapy.

MiR-145 inhibits the differentiation and proliferation of bone marrow stromal mesenchymal stem cells by GABARAPL1 in steroid-induced femoral head necrosis.

Steroid-induced osteonecrosis of femoral head (SANFH) involves impaired differentiation of bone marrow mesenchymal stem cells (BMSC), the mechanism of which is regulated by multiple microRNAs. Studies have shown that miR-145 is a key regulatory molecule of BMSC cells, but its mechanism in steroid-induced femur head necrosis remains unclear. The present study mainly explored the specific mechanism of miR-145 involved in SANFH. In this study dexamethasone, a typical glucocorticoid, was used to induce osteogenic differentiation of BMSC cells. Western blot, qPCR, CCK8 and flow cytometry were used to investigate the effects of miR-145 on the proliferation and differentiation of BMSC. The relationship between miR-145 and GABA Type A Receptor Associated Protein Like 1(GABARAPL1) was identified using dual luciferase reports and the effects of the two molecules on BMSC were investigated in vitro. The results showed that miR-145 was up-regulated in SANFH patients, while GABARAPL1 was down-regulated. Inhibition of miR-145 can improve apoptosis and promote proliferation and activation of BMSC. GABARAPL1 is a downstream target gene of miR-145 and is negatively regulated by miR-145. In conclusion, miR-145 regulates the proliferation and differentiation of glucocorticoid-induced BMSC cells through GABARAPL1 and pharmacologically inhibit targeting miR-145 may provide new aspect for the treatment of SANFH.

Bioinformatics-based study to identify immune infiltration and inflammatory-related hub genes as biomarkers for the treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease whose principal pathological change is aggressive chronic synovial inflammation; however, the specific etiology and pathogenesis have not been fully elucidated. We downloaded the synovial tissue gene expression profiles of four human knees from the Gene Expression Omnibus database, analyzed the differentially expressed genes in the normal and RA groups, and assessed their enrichment in functions and pathways using bioinformatics methods and the STRING online database to establish protein-protein interaction networks. Cytoscape software was used to obtain 10 hub genes; receiver operating characteristic (ROC) curves were calculated for each hub gene and differential expression analysis of the two groups of hub genes. The CIBERSORT algorithm was used to impute immune infiltration. We identified the signaling pathways that play important roles in RA and 10 hub genes: Ccr1, Ccr2, Ccr5, Ccr7, Cxcl5, Cxcl6, Cxcl13, Ccl13, Adcy2, and Pnoc. The diagnostic value of these 10 hub genes for RA was confirmed using ROC curves and expression analysis. Adcy2, Cxcl13, and Ccr5 are strongly associated with RA development. The study also revealed that the differential infiltration profile of different inflammatory immune cells in the synovial tissue of RA is an extremely critical factor in RA progression. This study may contribute to the understanding of signaling pathways and biological processes associated with RA and the role of inflammatory immune infiltration in the pathogenesis of RA. In addition, this study shows that Adcy2, Cxcl13, and Ccr5 have the potential to be biomarkers for RA treatment.

Potential In Vitro Tissue-Engineered Anterior Cruciate Ligament by Copolymerization of Polyvinyl Alcohol and Collagen.

BACKGROUND AND PURPOSE: Suitable tissue-engineered scaffolds to replace human anterior cruciate ligament (ACL) are well developed clinically as the development of tissue engineering. As water-soluble polymer compound, polyvinyl alcohol (PVA) has been wildly used as the materials to replace ACL. The aim of this study was to explore the feasibility of constructing tissue-engineered ACL by the copolymerization of PVA and collagen (PVA/COL). METHODS: PVA and COL were copolymerized at a mass ratio of 3:1. The pore size and porosity of the scaffold were observed by electron microscope. The maximum tensile strength of the scaffold was determined by electronic tension machine. The cytotoxicity of the scaffold was evaluated by MTT assay. The morphology of ACL cells cultured on the surface of the scaffold was observed by inverted microscope. The degradation of the scaffold was recorded in the rabbit model. RESULTS: The average pore size of the polymer scaffold was 100 to 150 µm and the porosity was about 90%. The maximum tensile strength of the scaffold material was 8.10 ±â€Š0.28 MPa. PVA/COL could promote the proliferation ability of 3T3 cells. ACL cells were successfully cultured on the surface of PVA/COL scaffold, with natural growth rate, differentiation, and proliferation. Twenty-four weeks after the plantation of scaffold, obvious degradations were observed in vivo. CONCLUSION: The model of in-vitro tissue-engineered ACL was successfully established by PVA/COL scaffolds.

Long noncoding RNA ZBED3-AS1 induces the differentiation of mesenchymal stem cells and enhances bone regeneration by repressing IL-1ß via Wnt/ß-catenin signaling pathway.

Bone regeneration, as a physiological process of bone formation, is regulated by multiple cytokines. Long noncoding RNAs are involved in the progress of bone formation. The present study investigated role by which ZBED3-AS1 acts to control the differentiation of mesenchymal stem cells (MSCs) and bone regeneration. Bioinformatics prediction and dual luciferase reporter gene assay identified putative ZBED3-AS1 binding sites on the 3'-untranslated region of interleukin-1ß (IL-1ß). Then, RNA immunoprecipitation and chromatin immunoprecipitation assays confirmed that ZBED3-AS1 could regulate the expression of IL-1ß by binding to the transcription factor CREB. Notably, ZBED3-AS1 was shown to negatively regulate IL-1ß expression. After model establishment in rats simulating bone injury, MSCs were isolated and delivered with ZBED3-AS1, Si-ZBED3-AS1, Si-IL-1ß, or DKK (inhibitor of Wnt/ß-catenin signaling pathway) to identify their roles in osteogenic differentiation by evaluating MSC colony formation and proliferation. Then, number of mineralized nodules, alkaline phosphatase (ALP) activity and osteocalcin (OCN) expression, and expression of osteogenesis-related genes were determined. Overexpression of ZBED3-AS1 or silencing of IL-1ß was shown to accelerate ectopic osteogenesis, as reflected by increasing the number of mineralized nodules, ALP activity, and OCN expression, and promoting MSC colony formation and proliferation. Additionally, ZBED3-AS1 activated the Wnt/ß-catenin signaling pathway by negatively regulating IL-1ß. IL-1ß inhibited osteogenic differentiation by suppressing the Wnt/ß-catenin signaling pathway. Furthermore, the effect of ZBED3-AS1 and IL-1ß on osteogenic differentiation was confirmed in vivo. Taken together, upregulation of ZBED3-AS1 could restore differentiation of MSCs and enhance bone regeneration via activation of Wnt/ß-catenin signaling pathway by repressing IL-1ß.

Angiopoietin-like 2 upregulation promotes human chondrocyte injury via NF-κB and p38/MAPK signaling pathway.

Several cellular and molecular processes participate in the pathologic changes of osteoarthritis (OA). However, the core molecular regulators of these processes are unclear, and no effective treatment for OA disease has been developed so far. ANGPTL2 is well known for its tissue remolding and pro-inflammation properties. However, the role of ANGPTL2 in osteoarthritis (OA) still remains unclear. To explore the expression level of ANGPTL2 in human OA cartilage and investigate the function of ANGPTL2 in human chondrocytes injury, qRT-PCR, western blot and immunohistochemistry were employed to investigate the expression of ANGPTL2 between human OA and normal cartilage samples. Next, human primary chondrocytes were treated with IL-1ß to mimic OA progress in vitro, and the expression of ANGPTL2 were tested by qRT-PCR and western blot. Furthermore, the effect of ANGPTL2 in the expression of pro-inflammation cytokines (IL-1ß, IL-6), proteolytic enzymes (MMP-1, MMP-13) and component of the cartilage matrix (COL2A1 and aggrecan) in human primary chondrocyte were explored by gain-of-function and loss-of-function methods. Finally, the nuclear factor kappa B (NF-κB) and p38/MAPK signaling pathways were also tested by western blot analysis. In this study, firstly, the expression level of ANGPTL2 was elevated both in human OA cartilage samples and IL-1ß stimulated human chondrocytes. Secondly, ANGPTL2 upregulation promotes extracellular matrix (ECM) degradation and inflammation mediator production in human chondrocytes. Finally, ANGPTL2 activated the NF-κB and p38/MAPK signaling pathways via integrin α5ß1. This study, for the first time, highlights that ANGPTL2 secreted by human chondrocytes plays a negative role in the pathogenesis of osteoarthritis, and it may be a potential therapeutic target in OA.

Suprapatellar versus infrapatellar approaches in the treatment of tibia intramedullary nailing: a retrospective cohort study.

BACKGROUND: Tibial shaft fractures are routinely managed with intramedullary nailing (IMN). An increasingly accepted technique is the suprapatellar (SP) approach. The purpose of this study was to compare the clinical and functional outcomes of knee joint after tibia IMN through an suprapatellar (SP) or traditional infrapatellar (IP) approach. METHODS: Retrospective analysis was performed in patients with tibial shaft fractures that were treated with IMN through a SP or IP approach between 01/01/2014 and 31/12/2016. The clinical and functional outcomes of the knee were assessed with the Hospital for Special Surgery (HSS) Knee Score. Secondary outcomes included the operation time and intraoperative blood loss. RESULTS: A total of 50 patients/fractures (26 IP and 24 SP) with a minimum follow-up of 15 months were evaluated. All fractures were OTA 42. No significant differences were found between the two groups in age, gender, side of fractures, operation time, intra-operative blood loss, and follow-up time. No significant difference was seen in HSS score (P = 0.62) between them. Sub analysis of all the HSS components scores revealed no significant differences between pain (P = 0.57), the stand and walk (P = 0.54), the need for walking stick (P = 0.60) and extension lag (P = 0.60). The other HSS components showed full scores (IP 10 vs. SP 10) in both approaches, including muscle force, flexion deformity and stability components. The range of motion (ROM) component score was superior in the IP group (P = 0.04) suggesting a higher ROM. CONCLUSIONS: Both SP and IP approach results in equivalent overall HSS knee scores. However, for the HSS component, the IP approach was superior to SP approach regarding the ROM.

Parallel comparison of fibroblast-like synoviocytes from the surgically removed hyperplastic synovial tissues of rheumatoid arthritis and osteoarthritis patients.

BACKGROUND: Fibroblast-like synoviocytes (FLS) are essential cellular components in inflammatory joint diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA). Despite the growing use of FLS isolated from OA and RA patients, a detailed functional and parallel comparison of FLS from these two types of arthritis has not been performed. METHODS: In the present study, FLS were isolated from surgically removed synovial tissues from twenty-two patients with OA and RA to evaluate their basic cellular functions. RESULTS: Pure populations of FLS were isolated by a sorting strategy based on stringent marker expression (CD45-CD31-CD146-CD235a-CD90+PDPN+). OA FLS and RA FLS at the same passage (P2-P4) exhibited uniform fibroblast morphology. OA FLS and RA FLS expressed a similar profile of cell surface antigens, including the fibroblast markers VCAM1 and ICAM1. RA FLS showed a more sensitive inflammatory status than OA FLS with regard to proliferation, migration, apoptosis, inflammatory gene expression and pro-inflammatory cytokine secretion. In addition, the responses of OA FLS and RA FLS to both the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) and the anti-inflammatory drug methotrexate (MTX) were also evaluated here. CONCLUSION: The parallel comparison of OA FLS and RA FLS lays a foundation in preparation for when FLS are considered a potential therapeutic anti-inflammatory target for OA and RA.

Minimally invasive internal fixator for unstable pelvic ring injuries with a pedicle screw-rod system: a retrospective study of 23 patients after 13.5 months.

PURPOSE: Pelvic ring fractures are challenging injuries and require effective treatment due to the frequently compromised patient condition. The aim of this study was to evaluate the outcome of unstable pelvic ring injuries treated with a minimally invasive pedicle screw-rod system. METHODS: Retrospective analysis was performed for patients with an unstable pelvic ring injury that were treated with a minimally invasive anterior internal pelvic fixator (INFIX) with or without a posterior pedicle screw-rod fixator (6/2012-4/2015). The quality of reduction was evaluated by the Tornetta and Matta criteria and the clinical outcome was evaluated by the Majeed scores. Further evaluation included the operation time, intraoperative blood loss, and complication rate. RESULTS: A total of 23 patients (12 males and 11 females) with a mean age of 37.6 years (range 10-65 years) and a follow-up of 13.5 months (6-27 months) were evaluated. The Tile classification showed 13 type B (B1 = 6, B2 = 4, and B3 = 3) and 10 type C (C1 = 7 and C2 = 3) fractures. Mean operation time and intraoperative blood loss were 24.8 min (20-30 min) and 20.4 ml (16-29 ml) for an anterior INFIX (n = 13), and 60 min (45-70 min) and 150 ml (115-168 ml) when combined with a posterior pedicle screw-rod fixator (n = 10). Quality of reduction was excellent in 13, good in 6, and fair in 4 patients, with no signs of heterotopic ossification. Clinical results after 6 months were excellent in 14 patients, good in 6, fair in 2, and poor in 1. Unilateral thigh paresthesia was seen in 2 patients which resolved after implant removal. CONCLUSIONS: The INFIX appears to be a safe and minimally invasive surgical technique which can effectively be combined with posterior pedicle screw-rod fixation. It also can be applied for the definitive treatment of vertically and/or rotationally unstable pelvic ring injuries, especially in severely compromised patients with a high mortality risk.

A case-control study and meta-analysis reveal the association between COX-2 G-765C polymorphism and primary end-stage hip and knee osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a popular arthrosis featured as pain, limited joint activity, and deformity. Cyclooxygenase-2 (COX-2) has been reported to be up-regulated in arthritic tissues and is integral to the progression of osteoarthritis (OA). Previous studies showed the COX-2 promoter G-765C polymorphism could influence COX-2 expression. However, the relationship between the variant and OA risk is contrasting. METHODS: We conducted a case-control study with 196 primary end-stage hip and knee OA cases and 196 controls in a Chinese Han population. Subsequently, we integrated this case-control study in a meta-analysis to acquire greater statistical power. The results from our case-control study using MassARRAY genotyping technology and binary logistic regression statistical methods. RESULTS: The variant carriers in the Chinese Han population had a lower primary end-stage hip and knee OA susceptibility (C vs G: OR = 0.350, 95%CI: 0.154-0.797, P = .012; GC vs GG: adjusted OR = 0.282, 95%CI: 0.118-0.676, P = .005). Stratification studies indicated that a higher GC frequency in women decreased not only knee OA susceptibility but also unilateral knee OA risk. The meta-analysis showed that the variant exhibited a significantly decreased OA risk through comparisons involving allelic, homozygous, heterozygous, and dominant models. CONCLUSION: Our findings suggest that the COX-2 G-765C polymorphism exerts a protective effect against primary end-stage knee osteoarthritis in a female Chinese Han population.

Inhibition of the p38-MAPK signaling pathway suppresses the apoptosis and expression of proinflammatory cytokines in human osteoarthritis chondrocytes.

This study aims to investigate the effects of p38-MAPK signaling pathway on the apoptosis and expression of proinflammatory cytokines in human osteoarthritis (OA) chondrocytes. Human articular cartilage specimens were obtained from 57 OA patients and 31 patients with lower extremity traumatic amputations. The expressions of p38-MAPK pathway-related proteins in cartilage tissue were detected by immunochemistry. Cultured chondrocytes isolated from human OA cartilage were assigned into the blank group, the IL-1ß group, the PD (PD980959, ERK pathway inhibitors)+IL-1ß group, the SB (SB203580, p38 pathway inhibitors)+IL-1ß group, and the SP (SP600125, JNK signaling pathway inhibitors)+IL-1ß group. Cell proliferation and apoptosis were detected by MTT assay and flow cytometry. Western blotting was used to detect the expressions of MAPK pathway-related proteins. The mRNA expressions of IL-1, IL-6, and TNF-α were detected by qRT-PCR. The positive rates of p-p38, p-JNK and p-ERK in OA cartilage were higher than those in normal cartilage. Compared with the blank group, cell proliferation rate was decreased, cell apoptotic rate was increased, the mRNA expressions of IL-1, IL-6, TNF-α and the expressions of p-p38, p-JNK and p-ERK were increased in the IL-1ß group, while opposite trends were observed in the PD+IL-1ß, SB+IL-1ß, and SP+IL-1ß groups. Our study provides evidence that inhibition of the p38-MAPK signaling pathway could suppress the apoptosis and expression of proinflammatory cytokines in human OA chondrocytes.