Secretion from adipose tissue of adipokines or adipocytokines, comprising of bioactive peptides or proteins, immune molecules and inflammatory mediators, exert critical roles in inflammatory ...arthritis and obesity. This review considers the evidence generated over the last decade regarding the effects of several adipokines including leptin, adiponectin, visfatin, resistin, chemerin and apelin, in cartilage and bone homeostasis in the pathogenesis of rheumatoid arthritis and osteoarthritis, which has important implications for obesity.
Resistin is a cysteine‐rich adipokine that promotes the release of inflammatory cytokines, particularly interleukin 1 beta (IL‐1β) and tumor necrosis factor alpha (TNF‐α), which are critical ...pro‐inflammatory mediators in osteoarthritis (OA) pathogenesis. We describe evidence of significantly higher levels of resistin, IL‐1β, and TNF‐α expression in OA knee synovial tissue compared with that from non‐OA knees. Resistin‐induced enhancement of IL‐1β and TNF‐α expression in human OA synovial fibroblasts (OASFs) were attenuated by MEK and ERK inhibitors, as well as their respective siRNAs. Our data reveal that resistin enhances the expression of TNF‐α and IL‐1β in OASFs by inhibiting miR‐149 expression via MEK and ERK signaling. Our findings elucidate the inter‐relationships between resistin and pro‐inflammatory mediators during OA pathogenesis and could help to facilitate the development of synovium‐targeted therapy in OA.
The current treatment of osteogenesis imperfecta (OI) is imperfect. Our study thus delves into the potential of using Dickkopf-1 antisense (DKK1-AS) to treat OI.
We analysed serum DKK1 levels and ...their correlation with lumbar spine and hip T-scores in OI patients. Comparative analyses were conducted involving bone marrow stromal cells (BMSCs) and bone tissues from wild-type mice, untreated OI mice, and OI mice treated with DKK1-ASor DKK1-sense (DKK1-S).
Significant inverse correlations were noted between serum DKK1 levels and lumbar spine (correlation coefficient = - 0.679, p = 0.043) as well as hip T-scores (correlation coefficient = - 0.689, p = 0.042) in OI patients. DKK1-AS improved bone mineral density (p = 0.002), trabecular bone volume/total volume fraction (p < 0.001), trabecular separation (p = 0.010), trabecular thickness (p = 0.001), trabecular number (p < 0.001), and cortical thickness (p < 0.001) in OI mice. DKK1-AS enhanced the transcription of collagen 1α1, osteocalcin, runx2, and osterix in BMSC from OI mice (all p < 0.001), resulting in a higher von Kossa-stained matrix area (p < 0.001) in ex vivo osteogenesis assays. DKK1-AS also reduced osteoclast numbers (p < 0.001), increased β-catenin and T-cell factor 4 immunostaining reactivity (both p < 0.001), enhanced mineral apposition rate and bone formation rate per bone surface (both p < 0.001), and decreased osteoclast area (p < 0.001) in OI mice. DKK1-AS upregulated osteoprotegerin and downregulated nuclear factor-kappa B ligand transcription (both p < 0.001). Bone tissues from OI mice treated with DKK1-AS exhibited significantly higher breaking force compared to untreated OI mice (p < 0.001).
Our study elucidates that DKK1-AS has the capability to enhance bone mechanical properties, restore the transcription of osteogenic genes, promote osteogenesis, and inhibit osteoclastogenesis in OI mice.
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.
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.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction: Human chondrosarcomas (CS; a malignant cartilage-forming bone tumor) respond poorly to chemotherapy and radiation treatment, resulting in high morbidity and mortality rates. Expanded ...treatment options are urgently needed.
Areas covered: This article updates our 2014 review, in which we evaluated the CS treatments available at that time and potential treatment options under investigation. Since then, advances in research findings, particularly from Chinese herbal medicines, may be bringing us closer to more effective therapies for CS. In particular, promising findings have been reported from research targeting platelet-derived growth factor receptor.
Expert opinion: Few treatment options exist for CS; chemotherapy is not even an option for unresectable disease, in which 5-year survival rates are just 2%. New information about the multitude of genes and signaling pathways that encourage CS growth, invasion and metastasis are clarifying how certain signaling pathways and plant-derived active compounds, especially molecularly-targeted therapies that inhibit the PDGF receptor, interfering with these biological processes. This review summarizes discoveries from the last 5 years and discusses how these findings are fueling ongoing work into effectively dealing with the disease process and improving the treatment of CS.
This study aimed to evaluate the systemic impact of periodontitis, previously considered a local disease, on cancer occurrence. We enrolled 683,854 participants, comparing cancer incidence among ...those with and without periodontitis and assessing the impact of periodontal treatment on cancer risk. Regardless of gender, age, Charlson comorbidity index, or the use of non-steroidal anti-inflammatory drugs, periodontitis patients had a lower overall cancer risk than controls. However, men with periodontitis had a higher risk of prostate cancer (adjusted hazard ratio aHR = 1.22; 95% confidence interval CI = 1.10-1.35), and both men and women had a higher risk of thyroid cancer (women: aHR = 1.20, 95%CI = 1.04-1.38; men: aHR = 1.51, 95% CI = 1.15-1.99). Patients with periodontitis who received treatment showed a reduced cancer risk (aHR = 0.41; 95% CI = 0.38-0.44) compared to untreated patients. Proper treatment for periodontitis may lower an individual's cancer risk more than if they did not have the disease at all, suggesting that periodontitis is a modifiable risk factor for cancer.
Micro-ribonucleic acids (miRNAs) are involved in osteoarthritis (OA) pathogenesis and clock-controlled genes (CCGs) regulation. However, the interaction between miRNAs and CCGs remains unclear.
Human ...OA samples were used to assess CCGs expression. Cartilage-specific miR-128a knockout mouse model was established to investigate miR-128a′s role in OA pathogenesis. Destabilization of the medial meniscus (DMM) model was employed to simulate OA.
Transcription levels of nuclear receptor subfamily 1 group D member 2 (NR1D2) were lower in both human OA samples and wild-type mice undergoing DMM compared to non-OA counterparts. MiR-128a knockout mice showed reduced disturbances in micro-computed tomographic and kinematic parameters following DMM, as well as less severe histologic cartilage loss. Immunohistochemistry staining revealed a lesser decrease in NR1D2-positive chondrocytes after DMM in miR-128a knockout mice than in wild-type mice. NR1D2 agonist rescued the suppressed expression of cartilage anabolic factors and extracellular matrix deposition caused by miR-128a precursor.
Cartilage-specific miR-128a knockout mice exhibited reduced severity, less disrupted kinematic parameters, and suppressed NR1D2 expression after DMM. NR1D2 enhanced the expression of cartilage anabolic factors and extracellular matrix deposition. These findings highlight the potential of employing miR-128a and CCG-targeted therapy for knee OA.
Aim. We wish to investigate the therapeutic potential of a single-session high-energy extracorporeal shock wave therapy (ESWT) on the rotator cuff lesions with shoulder stiffness. Patients and ...Methods. Thirty-seven patients afflicted with rotator cuff lesions with shoulder stiffness were randomized to receive either shockwave or sham treatment based on statistical randomization. In the shockwave group, we used Orthospec™ Extracorporeal Shock Wave Therapy 3000 impulse 24 kV (0.32 mJ/mm2) focused at two points as one session. The sham intervention entailed the use of the device in which the silicone pad was removed from the stand-off device. The visual analogue scale (VAS), muscle power of the shoulder, Constant and Murley score (CMS), and range of motion (ROM) of the shoulder were assessed for all patients. Ten milliliters of peripheral venous blood was obtained from every participant for the measurements of markers for inflammation, tissue regeneration, angiogenesis, and substance P before and at 1 week and 4 weeks after intervention. Results. The ESWT group has significantly better VAS, muscle power, CMS, and ROM at 6 and 12 months after intervention. No between-group differences were observed before as well as 1 and 4 weeks after intervention in the selected biomarkers. Conclusion. ESWT may be a good adjuvant for the treatment of rotator cuff lesions with shoulder stiffness.
Living donor liver transplantation (LDLT) is lifesaving, but can lead to osteoporosis and fractures. In our 3-year study of 25 LDLT recipients, we observed significant reductions in lumbar spine and ...femoral neck T scores, along with bone resorption marker reductions and liver regeneration marker increases. Serum calcium levels increased, while osteoprotegerin (OPG) decreased and Dickkopf-related protein 1 (DKK-1) increased. Patients who suffered fractures within 3 years of LDLT had higher serum OPG, lower serum nuclear factor kappa B ligand (RANKL), a higher OPG/RANKL ratio and higher serum DKK-1 levels. OPG, RANKL, OPG/RANKL ratio and DKK-1 levels before LDLT predicted hip or spine fractures within three years after LDLT. Further research is necessary to determine the optimal level of osteoclastic activity for preventing fracture onset.
PDF
