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Repairing damaged articular cartilage is particularly challenging because of the limited ability of cartilage to perform self-repair. Intra-articular injections of N-acetylglucosamine (GlcNAc) comprise a method of repairing full-thickness articular cartilage defects in the rabbit knee joint model. To date, the effects of administration of GlcNAc and hyaluronic acid (HA) have been investigated only in the context of osteoarthritis treatment. Therefore, we evaluated the therapeutic effects of using cell-free porous poly lactic-co-glycolic acid (PLGA) graft implants and intra-articular injections of GlcNAc or HA in a rabbit model of osteochondral regeneration to investigate whether they have the potential for inducing osteochondral regeneration when used alone or simultaneously. Twenty-four rabbits were randomized into one of four groups: the scaffold-only group (PLGA), the scaffold with intra-articular injections of GlcNAc (PLGA+G) group, twice per week for four weeks; the scaffold with intra-articular injections of HA group (PLGA+HA) group, once per week for three weeks; and the scaffold with intra-articular injections of GlcNAc and HA (PLGA+G+HA) group, once per week for three weeks. Knees were evaluated at 4 and 12 weeks after surgery. At the end of testing, only the PLGA+G+HA group exhibited significant bone reconstruction, chondrocyte clustering, and good interactions with adjacent surfaces at 4 weeks. Additionally, the PLGA+G+HA group demonstrated essentially original hyaline cartilage structures that appeared to have sound chondrocyte orientation, considerable glycosaminoglycan levels, and reconstruction of the bone structure at 12 weeks. Moreover, the PLGA+G+HA group showed organized osteochondral integration and significantly higher bone volume per tissue volume and trabecular thickness. However, there were no significant differences between the PLGA+G and PLGA+HA groups except for gap formation on subchondral bone in the PLGA+G group. This study demonstrated that PLGA implantation combined with intra-articular injections of GlcNAc and HA allowed for cartilage and bone regeneration and significantly promoted osteochondral regeneration in rabbits without supplementation of exogenous growth factors. And the combination of this two supplements with PLGA scaffold could also prolong injection interval and better performance than either of them alone for the reconstruction of osteochondral tissue in the knee joints of rabbits. [ABSTRACT FROM AUTHOR]

Total knee arthroplasty (TKA) is a well-established modality for the treatment of advanced knee osteoarthritis (OA). However, the detrimental effects of intramedullary reaming used in conventional TKA for distal femur cutting are of concern. Avoiding intramedullary reaming with the use of computer-assisted navigation TKA can not only provide superior prosthetic alignment, but also mitigate perioperative blood loss and the dissipation of marrow emboli. We quantified local and systemic concentrations of inflammation markers for both techniques. Forty-four participants undergoing computer-assisted navigation and 53 receiving conventional TKA for advanced knee OA were recruited between 2013/02/08 and 2015/12/09. Blood samples were collected from all participants at baseline then again at 24 and 72 hours postoperatively and analyzed by ELISA for interleukin 6 (IL-6), IL-10, tumor necrosis factor alpha (TNF-α) and transforming growth factor beta 1 (TGF-β1); these markers were also measured in Hemovac drain fluid collected at 24 and 72 hours. Serum levels of IL-6, IL-10, TNF-α and TGF-β1(unit for all markers: pg/mL) were increased from baseline by smaller increments in the navigation TKA cohort compared with the conventional TKA group at 24 hours (17.06 vs 29.39, p = 0.02; 0.51 vs 0.83, p = 0.16; –0.04 vs 0.36, p < 0.01 and –48.18 vs 63.24, p< 0.01, respectively) and at 72 hours (12.27 vs 16.87, p = 0.01; –0.40 vs 0.48, p < 0.01; 0.58 vs 0.98, p = 0.07 and –55.16 vs 63.71, p < 0.01, respectively). IL-10 levels in drainage fluids collected 24 hours after TKA were also significantly lower in the navigation group versus the conventional TKA group (8.55 vs 12.32, p < 0.01). According to our evidence, the merits of computer-assisted navigation TKA are augmented by low levels of inflammation markers. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is manifested by synovial inflammation and cartilage destruction that is directly linked to synovitis, joint swelling and pain. In the light of the role of synovium in the pathogenesis and the symptoms of OA, synovium-targeted therapy is a promising strategy to mitigate the symptoms and progression of OA. Transforming growth factor beta 1 (TGF-β1), a secreted homodimeric protein, possesses unique and potent anti-inflammatory and immune-regulatory properties in many cell types. Heme oxygenase 1 (HO-1) is an inducible anti-inflammatory and stress responsive enzyme that has been proven to prevent injuries caused by many diseases. Despite the similar anti-inflammatory profile and their involvement in the pathogenesis of arthritic diseases, no studies have as yet explored the possibility of any association between the expression of TGF-β1 and HO-1. Methodology/Principal findings: TGF-β1-induced HO-1 expression was examined by HO-1 promoter assay, qPCR, and Western blotting. The siRNAs and enzyme inhibitors were utilized to determine the intermediate involved in the signal transduction pathway. We showed that TGF-β1 stimulated the synthesis of HO-1 in a concentration- and time-dependent manner, which can be mitigated by blockade of the phospholipase (PLC)γ/protein kinase C alpha (PKC)α pathway. We also showed that the expression of miRNA-519b, which blocks HO-1 transcription, is inhibited by TGF-β1, and the suppression of miRNA 519b could be reversed via blockade of the PLCγ/PKCα pathway. Conclusions/Significance: TGF-β1 stimulated the expression of HO-1 via activating the PLCγ/PKCα pathway and suppressing the downstream expression of miRNA-519b. These results may shed light on the pathogenesis and treatment of OA. [ABSTRACT FROM AUTHOR]

Background/Objective: Nicardipine is a calcium channel blocker that has been widely used to control blood pressure in severe hypertension following events such as ischemic stroke, traumatic brain injury, and intracerebral hemorrhage. However, accumulating evidence suggests that inflammatory processes in the central nervous system that are mediated by microglial activation play important roles in neurodegeneration, and the effect of nicardipine on microglial activation remains unresolved. Methodology/Principal Findings: In the present study, using murine BV-2 microglia, we demonstrated that nicardipine significantly inhibits microglia-related neuroinflammatory responses. Treatment with nicardipine inhibited microglial cell migration. Nicardipine also significantly inhibited LPS plus IFN-γ-induced release of nitric oxide (NO), and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, nicardipine also inhibited microglial activation by peptidoglycan, the major component of the Gram-positive bacterium cell wall. Notably, nicardipine also showed significant anti-neuroinflammatory effects on microglial activation in mice in vivo. Conclusion/Significance: The present study is the first to report a novel inhibitory role of nicardipine on neuroinflammation and provides a new candidate agent for the development of therapies for inflammation-related neurodegenerative diseases. [ABSTRACT FROM AUTHOR]