78 patients (41 male and 37 female) with a revision total knee or hip arthroplasty were enrolled in this prospective study to evaluate the role of new laboratory markers in the diagnostic of deep implant infection. The average age at the time of surgery was 64 years. Based on intraoperative cultures, 21 patients had a septic and 57 patients had an aseptic revision total joint arthroplasty. White blood cell counts, erythrocyte sedimentation rate, C-reactive protein levels, interleukin-6, procalcito-nin and TNF-alpha were measured in preoperative blood samples. Diagnostic cut of values were determined by Receiver Operating Characteristic curve analysis. If patients with rheumatoid arthritis and other concomitant infections are excluded the C-reactive protein (> 3.2md/dl) and interleukin 6 (> 12 pg/ml) have the highest sensitivity (0.95). Interleukin 6 is less specific than the C-reactive protein (0.87 versus 0.96). Combining C-reactive protein and interleukin identifies all patients with deep implant infection. Procalcitonin (> 0.3 ng/ml) and TNF-alpha (> 40 ng/ml) are very specific (0.98 versus 0.94)) but have a low sensitivity (0.33 versus 0.43). The combination of C-reactive protein and interleu-kin 6 is an excellent screening tests for deep implant infection. Highly specific marker like procalcitoninn as well as preoperative joint aspiration might be useful to identify patients with true positive CRP and/or interleu-kin 6 levels

Aim

One of the most accurate and inexpensive tests in detection of prosthetic joint infection (PJI) is synovial fluid white blood cell (WBC) count and differential. Since leukocytes produce many different interleukins (IL) in situation of PJI, we hypothesized that ILs could be even more accurate in detection of PJI. The aim of the study was to test, if the synovial fluid IL-6 level is superior to WBC count and differential in detection of PJI.

Aims. Tert-butylhydroquinone (tBHQ) has been identified as an inhibitor of oxidative stress-induced injury and apoptosis in human neural stem cells. However, the role of tBHQ in osteoarthritis (OA) is unclear. This study was carried out to investigate the role of tBHQ in OA. Methods. OA animal model was induced by destabilization of the medial meniscus (DMM). Different concentrations of tBHQ (25 and 50 mg/kg) were intraperitoneally injected in ten-week-old female mice. Chondrocytes were isolated from articular cartilage of mice and treated with 5 ng/ml lipopolysaccharide (LPS) or 10 ng/ml interleukin 1 beta (IL-1β) for 24 hours, and then treated with different concentrations of tBHQ (10, 20, and 40 μM) for 12 hours. The expression levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in blood were measured. The expression levels of interleukin 6 (IL-6), IL-1β, and tumour necrosis factor alpha (TNF-α) leptin in plasma were measured using enzyme-linked immunoabsorbent assay (ELISA) kits. The expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signalling pathway proteins, and macrophage repolarization-related markers, were detected by western blot. Results. Tert-butylhydroquinone significantly attenuated cartilage destruction in DMM-induced mice in vivo. It demonstrated clear evidence of inhibiting IL-1β-induced chondrocyte apoptosis, inflammation, and differentiation defect in vitro. Meanwhile, tBHQ inhibited LPS-induced activation of NF-κB and MAPK signalling pathways, and also inhibited LPS-induced reactive oxygen species production and macrophages repolarization in vitro. Conclusion. Taken together, tBHQ might be a potential therapeutic strategy for protecting against OA development. Cite this article: Bone Joint Res 2021;10(11):704–713

Cite this article: Bone Joint Res 2023;12(3):199–201.

Aims

Osteoarthritis (OA) is a prevalent joint disorder with inflammatory response and cartilage deterioration as its main features. Dihydrocaffeic acid (DHCA), a bioactive component extracted from natural plant (gynura bicolor), has demonstrated anti-inflammatory properties in various diseases. We aimed to explore the chondroprotective effect of DHCA on OA and its potential mechanism.

Aims

This study aimed, through bioinformatics analysis, to identify the potential diagnostic markers of osteoarthritis, and analyze the role of immune infiltration in synovial tissue.

Introduction and Objective. Chronic tendinopathy is a multifactorial disease and a common problem in both, athletes and the general population. Mechanical overload and in addition old age, adiposity, and metabolic disorders are among the risk factors for chronic tendinopathy but their role in the pathogenesis is not yet unequivocally clarified. Materials and Methods. Achilles tendons of young (10 weeks) and old (100 weeks) female rats bred for high (HCR) and low (LCR) intrinsic aerobic exercise capacity were investigated. Both Achilles tendons of 28 rats were included and groups were young HCR, young LCR, old HCR, and old LCR (n = 7 tendons per group/method). In this rat model, genetically determined aerobic exercise capacity is associated with a certain phenotype as LCR show higher body weight and metabolic dysfunctions in comparison to HCR. Quantitative real-time PCR (qPCR) was used to evaluate alterations in gene expression. For histological analysis, semi-automated image analysis and histological scoring were performed. Results. Age-related downregulation of tenocyte marker genes (Tenomodulin), genes related to matrix modelling and remodeling (Collagen type 1, Collagen type 3, Elastin, Biglycan, Fibronectin, Tenascin C), and Transforming growth factor beta 3 (Tgfb3) were detected in tendons from HCR and LCR. Furthermore, inflammatory marker Cyclooxygenase 2 (Cox2) was downregulated, while Microsomal prostaglandin E synthase 2 (Ptges2) was upregulated in tendons from old HCR and old LCR. No significant alteration was seen in Interleukin 6 (Il6), Interleukin 1 beta (Il1b), and Tumor necrosis factor alpha (Tnfa). Histological analysis revealed that Achilles tendons of old rats had fewer and more elongated tenocyte nuclei compared to young rats, indicating a reduced metabolic activity. Even though higher content of glycosaminoglycans as a sign of degeneration was found in tendons of old HCR and LCR, no further signs of tendinopathy were detectable in histological evaluation. Conclusions. Overall, aging seems to play a prominent role in molecular and structural alterations of Achilles tendon tissue, while low intrinsic exercise capacity did not cause any changes. Even though tendinopathy was not present in any of the groups, some of the shown age-related changes correspond to single characteristics of chronic tendon disease. This study gives an insight into tendon aging and its contribution to molecular and cellular changes in Achilles tendon tissue

Background. About 85% of the patients with low back pain seeking medical care have nonspecific low back pain (NsLBP), implying that no definitive cause can be identified. Many pain conditions are linked with elevated serum levels of (pro-)inflammatory biomarkers. Purpose. To unravel the etiology and get better insight in the prognosis of NsLBP, the aim of this study was to assess the association between (pro-)inflammatory biomarkers and the presence and severity of NsLBP. Methods. A systematic literature search was made in Embase, Medline, Cinahl, Web-of-science, and Google scholar up to January 19th 2017. Included were studies reporting on patients >18 years with NsLBP, in which one or more pro-inflammatory biomarkers were measured in blood plasma. The methodological quality of the included studies was assessed using the Newcastle Ottawa Scale (NOS). A best-evidence synthesis was used to summarize the results from the individual studies. Results. Included were 10 studies which assessed 4 different (pro-)inflammatory biomarkers. For the association between the presence of NsLBP and C-reactive protein (CRP), interleukin 6 (IL-6) and tumor necrosis factor (TNF)-α limited, conflicting and moderate evidence, respectively, was found. For the association between the severity of NsLBP and CRP and IL-6, moderate evidence was found. For the association between the severity of NsLBP and TNF-α and RANTES conflicting and limited evidence, respectively, was found. Conclusions. This study found moderate evidence for i) a positive association between the (pro-)inflammatory biomarkers CRP and IL-6 and the severity of NsLBP, and ii) a positive association between TNF-α and the presence of NsLBP. No conflicts of interest. No funding obtained

Objective. Mortality rates reported by the National Joint Registry for England and Wales (NJR) were higher following cemented total knee replacement (TKR) compared with uncemented procedures. The aim of this study is to examine and compare the effects of cemented and uncemented TKR on the activation of selected markers of inflammation, endothelium, and coagulation, and on the activation of selected cytokines involved in the various aspects of the systemic response following surgery. Methods. This was a single centre, prospective, case-control study. Following enrolment, blood samples were taken pre-operatively, and further samples were collected at day one and day seven post-operatively. One patient in the cemented group developed a deep-vein thrombosis confirmed on ultrasonography and was excluded, leaving 19 patients in this cohort (mean age 67.4, (. sd. 10.62)), and one patient in the uncemented group developed a post-operative wound infection and was excluded, leaving 19 patients (mean age 66.5, (. sd. 7.82)). Results. Both groups had a similar response with regards to the levels of C-reactive protein (CRP), interleukin 6 (IL-6) and tumour necrosis factor-alpha (TNFα). CD40 levels rose significantly on the cemented group over day one to day seven compared with that of the uncemented group, which occurred over the first 24 hours. The CD14/42a levels demonstrated a statistically significant increase in the cemented group (p < 0.001 first 24 hours and p = 0.02 between days one and seven). . Conclusions. The uncemented and cemented groups demonstrated significant changes in the various parameters measured at various time points but apart from CD14/42a levels, there was no significant difference in the serum markers of inflammation, coagulation and endothelial dysfunction following cemented TKR. Cite this article: Bone Joint Res 2014;3:108–16

Cancer associated bone pain (CIBP) is a common event in patients with advanced disease with bone metastases (BM), significantly impairing their quality of life. Treatment options are limited and mainly based on the use of opioids with unacceptable side effects. Local acidosis is a well-known cause of pain since it directly stimulates nociceptors that express acid-sensing ion channels and densely innervate bone. In BM, local acidosis derives from osteoclast bone resorption activity and from the acidification by glycolytic tumor cells. Here we speculated that the pH lowering of intratumoral interstitial fluid also promotes nociceptors sensitization and hyperalgesia through the activation of cells of mesenchymal origin in BM microenvironment that might release inflammatory and nociceptive mediators. As a model of breast cancer that can metastatise to the bone we used MDA-MB-231 (MDA), and a subclone with a higher tendency to form osteolytic BM (bmMDA). We evaluated the basal expression of proton pumps/ion transporters by Real-Time PCR (Q-RT-PCR). To evaluate the effect of extracellular acidosis on mesenchymal tumor-associated stroma, we used human osteoblast primary cultures from healthy donors and cancer-associated fibroblasts isolated with specific immunobeads from the tumor biopsies of patient with BM. We exposed the cells to pH 6.8 medium at different time points (between 3 to 24 hours). After the short-term incubation with acidosis, for the expression of and acid-sensing ion channels, inflammatory cytokines and nociceptive mediators that can produce hyperalgesia, we used both a wide screening through a deep-sequencing approach and Q-RT-PCR, and ELISA. Xenograft for osteolytic BM induced by intratibial injection of bmMDA were treated with Omeprazole and monitored for CIBP through several cognitive tests. We found a significantly higher extracellular proton efflux and expression of proton pumps/ion transporters associated with the acid-base balance, the monocarboxylate transporter 4 (MCT4), the carbonic anhydrase (CA9), and the vacuolar ATPase (V-ATPase) V. 1. G. 1. subunit, and V. 0. c subunitin bmMDA, a subclone that is prone to form BM in respect to the parental cell line MDA-MB-231. In mesenchymal stromal cells, osteoblasts and cancer-associated fibroblasts, the incubation with pH 6.8 induced the expression of the achid-sensing ion channels AISC3/ACCN3 and AICS4/ACCN4, as well as of the nociceptive modulators nerve growth factor (NGF), Brain-derived neurotrophic factor (BDNF), and of the inflammatory cytokines interleukin 6 (IL6) and 8 (IL8), and Chemokine (C-C motif) ligand 5 (CCL5). Furthermore, the targeting of V0c subunit to inhibit intratumoral acidification significantly reduced CIBP in mice model of BM. In this study we demonstrated for the first time that, in addition to the direct acid-sensing neuronal stimulation, the acidic microenvironment of BM causes hyperalgesia through the activation of an inflammatory reaction in the tumor-associated mesenchymal stroma at the tumor site, thereby offering as a new target for palliative treatment in advanced cancer

The aim of this study was to examine the effects of cement in total knee arthroplasty on markers of inflammation and endothelial dysfunction, as surrogate markers for enhanced risk of vascular disease or precipitation of acute vascular events post-operatively. A total of 36 patients were recruited, with 18 in each of the cemented and uncemented groups. Both groups were matched for age, sex and body mass index. Venous blood samples were taken pre-operatively, day 1 and day 7 post-operatively. Serum levels of interleukin 6 (IL6), tumour necrosis factor (TNF□?, e-selectin, Von willebrand factor (vWF), tissue plasminogen activator (tPA) and soluble CD40 ligand were analysed. Also, real time analysis of the expression of CD40 and CD14/CD42a aggregates on monocytes was carried out using flow cytometry. Patients were excluded from the study if there were signs of either superficial or deep infection. The only variable to demonstrate a significant difference between the two groups was the CD1442a count. There was a significant difference in the first 24 hours (p=0.00) and from day 1 to day 7 (p=0.02). Our study suggests that the use of bone cement causes a significant rise in CD1442a count which has been linked to atherothrombosis and acute coronary syndromes. These changes may explain the increased incidence of venous thrombosis and thromboembolism post-operatively. However more research required in this field to delineate the exact pathways involved

Aim. This study aimed to assess whether the severity of symptoms (assessed with the Oxford Hip Score (OHS)) can relate to the levels of mRNA expression of markers for muscle inflammation (tumour necrosis factor alpha (TNFα), interleukin 6 (IL-6)) in the proximal vastus lateralis (VL) of patients with severe OA undergoing THR. Methods. Following local research ethics approval and informed consent, 17 patients were prospectively recruited. Muscle biopsies were obtained from the proximal VL (accessed through the surgical wound) intraoperatively whilst the OHS questionnaire was administered preoperatively. mRNA expression for TNFα and IL-6 was assessed using the reverse transcriptase polymerase chain reaction (RT-PCR). The median OHS was used for stratification, with patients above the median classed as having moderate symptoms (MS) and those below classed as having severe symptoms (SS). The effect of SS on muscle inflammation was assessed with relative quotient (RQ) comparison of SS vs. MS mRNA expression. Results. Patients recruited were (mean (SD)) 65.3(8.8) years old in men (n=9) and 59.8 (13.3) years old in women (n=9). The median OHS was 24 (range 10–32) with SS < 24 (n=10) and MS ≥ 24 (n=7). In comparison to the MS group, the SS group had increased TNFα expression (+28% (RQ=1.28, p=0.35)) with reduced IL-6 expression (−44% (RQ=0.56, p=0.35), though neither of these reached statistical significance. Conclusions. Muscle inflammation is not clearly correlated to symptoms in this group. Preoperative subjective functional deficit appears independent of muscle inflammation in patients with hip osteoarthritis

Aims

Pellino1 (Peli1) has been reported to regulate various inflammatory diseases. This study aims to explore the role of Peli1 in the occurrence and development of osteoarthritis (OA), so as to find new targets for the treatment of OA.

Aim. To examine the effects of total knee arthroplasty on markers of inflammation and endothelial dysfunction, as surrogate markers for enhanced risk of vascular disease or precipitation of acute vascular events post-operatively. Methods. All patients undergoing an elective uncemented total knee arthroplasty at a district general hospital were approached at the pre-assessment clinic. The study was explained and the patients were enrolled into the study following written consent. Venous blood samples were taken pre-operatively, day 1 and day 7 post-operatively. Serum levels of interleukin 6 (IL6), tumour necrosis factor (TNF??, e-selectin, Von willebrand factor (vWF), tissue plasminogen activator (tPA) and soluble CD40 ligand were analysed. Also, real time analysis of the expression of CD40 and CD14/CD42a aggregates on monocytes was carried out using flow cytometry. Patients were excluded from the study if there were signs of either superficial or deep infection. Results. Significant rises were seen with vWF, tPA and sCD40L levels up to day 7 (p= 0.01, 0.00. 0.00 respectively). IL6, e-selectin and TNF? levels were also significantly raised up to day 7 (p= 0.017, 0.031, 0.00). Analysis of the flow cytometry data revealed significant rises in the expression of CD40 (p= 0.006) and CD14/CD42a (P= 0.013) on monocytes over the same time period. Conclusion. Our study strongly suggests that patients undergoing an uncemented total knee arthroplasty provokes the release of vasoactive substances within the vasculature. These changes may explain the increased incidence of venous thrombosis and thromboembolism post-operatively as well as a potential increased risk of arterial thrombosis and sequelae from atherosclerotic plaque rupture

We removed 23 Charité artificial discs in 19 patients due to severe back-and legpain and performed an anterior as well posterior fusion. Mean interval between insertion and retrieval is 8,4 years (3,0–16,0 years). The mean age at retrieval is 49,4 years (40–72 years). The cause of persistent or recurrent pain was one or more of several problems thought to be related to the pain: subsidence, migration, wear with or without breakage of the metal marker ring, facetjoint or adjacent degeneration. In all cases wear of the polyethylene core was seen in major or minor degree. The wear was related to posterior impingement possibly due to hyperlordosis and extension instability and was subsequently more pronounced in the peripheral rim than in the central dome. Also a relationship was noted to in vivo oxidation of the polyethylene, especially in the rim. In the periprosthetic tissue an inflammatory reaction was found, more in the severe wear cases. Polyethylene loaded macrophages were seen, also polyethylene particles lying freely in the tissue. The macrophages proved positive for Interleukin 6. The wear pattern and the inflammatory reaction resembles the pattern seen in total hips and knees. Probably a substantial number of patients will exhibit these wear changes some years after insertion. It is questionable whether changes in sterilization and packaging and better insertion and sizing techniques will prevent wear development in the future

Aims

To investigate the optimal thresholds and diagnostic efficacy of commonly used serological and synovial fluid detection indexes for diagnosing periprosthetic joint infection (PJI) in patients who have rheumatoid arthritis (RA).

Osteoarthritis of the hip exhibits progressive degeneration of articular cartilage frequently resulting in total hip arthroplasty (THA). Expression of cytokines such as tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL6) is increased in the synovium and articular cartilage of these patients. Furthermore, these cytokines have been shown to have a negative regulatory effect on chondrocyte proliferation and articular cartilage metabolism. We investigated the frequency of a G/C polymorphism at position −174 of the promoter region of the IL-6 gene and a G/A polymorphism at position −308 of the TNF alpha gene, both of which cause increased expression of these cytokines. We observed that the G variant of the IL6 gene was significantly higher in patients who had undergone revision THA compared to controls (P=0.05). It was also elevated in primary THA patients compared to controls. The G/A polymorphism in TNF alpha was not significantly associated with THA; however, this may reflect the lower incidence of this polymorphism in the population. These results suggest that an alteration in cytokine expression produced by the IL6 −174G/C mutation may have a role in the aetiology of osteoarthritis and the outcome of total hip arthroplasty

Aims

Staphylococcus aureus is a major cause of septic arthritis, and in vitro studies suggest α haemolysin (Hla) is responsible for chondrocyte death. We used an in vivo murine joint model to compare inoculation with wild type S. aureus 8325-4 with a Hla-deficient strain DU1090 on chondrocyte viability, tissue histology, and joint biomechanics. The aim was to compare the actions of S. aureus Hla alone with those of the animal’s immune response to infection.

Aims: To examine the relationship between the Interleukin 6 (IL-6) −174 G> C promoter polymorphism and exercise-induced femoral cortical bone resorption. Methods: The skeletal response to exercise was assessed in 130 male Caucasian army recruits. Five cross-sectional magnetic resonance images of the right femur were obtained before and after a 10 week period of basic physical training, and changes in cross-sectional cortical area calculated. Recruits were genotyped for the −174 G> C IL-6 promoter polymorphism. Results: Genotype frequencies (GG 36%, GC 47%, CC 22 17%) were in Hardy-Weinberg Equilibrium. The mean percentage change in proximal femoral cross sectional cortical area was strongly IL-6 genotype-dependent, with GG homozygotes losing 6.8 ± 3.82% in cortical area, GC gaining +5.5 ± 4.88%, and CC gaining +17.3 ± 9.46% (p=0.007 for linear trend). These changes persisted throughout the right femur and were significant in the femur as a whole (p=0.03). Conclusion: This study demonstrates a linear relationship between a functional polymorphism in the IL-6 gene and femoral cortical remodelling during strenuous physical exercise. Previous studies have suggested an important role for IL-6 in the regulation of bone mass in postmenopausal women, and in the invasion of bone by metastatic tumour deposits. These data extend these observations to the regulation of bone mass in healthy males, supporting a fundamental role for IL-6 in the regulation of bone mass and bone remodelling in humans