Aims. The preoperative diagnosis of periprosthetic joint infection (PJI) remains a challenge due to a lack of biomarkers that are both sensitive and specific. We investigated the performance characteristics of polymerase chain reaction (PCR),
Synovial fluid white blood cell (WBC) count and percentage of polymorphonuclear cells (%PMN) are elevated at periprosthetic joint infection (PJI). Leucocytes produce different interleukins (IL), including IL-6, so we hypothesized that synovial fluid IL-6 could be a more accurate predictor of PJI than synovial fluid WBC count and %PMN. The main aim of our study was to compare the predictive performance of all three diagnostic tests in the detection of PJI. Patients undergoing total hip or knee revision surgery were included. In the perioperative assessment phase, synovial fluid WBC count, %PMN, and IL-6 concentration were measured. Patients were labeled as positive or negative according to the predefined cut-off values for IL-6 and WBC count with %PMN. Intraoperative samples for microbiological and histopathological analysis were obtained. PJI was defined as the presence of sinus tract, inflammation in histopathological samples, and growth of the same microorganism in a minimum of two or more samples out of at least four taken.Aims
Methods
This prospective study evaluates the role of new laboratory markers in the diagnosis of deep implant infection in 78 patients (41 men and 37 women) with a revision total knee or hip replacement. The mean age at the time of operation was 64.0 years (19 to 90). Intra-operative cultures showed that 21 patients had a septic and 57 an aseptic total joint replacement. The white blood cell count, the erythrocyte sedimentation rate and levels of C-reactive protein,
Confirming clinical evidence, we recently demonstrated in a rodent model that a severe trauma which induces an acute systemic inflammation considerably impairs fracture healing.
Background: Infection diagnosis in THA remains difficult in some cases. Intraoperative analysis of frozen sections is related to the high sensitivity, specificity, positive predictive value, negative predictive value and accuracy. However, it is a technically demanding procedure and is not a universally accepted method. In the present study, we compared
Purpose. Many studies have found associations between laboratory biomarkers and periprosthetic joint infection (PJI), but it remains unclear whether these biomarkers are clinically useful in ruling out PJI. This meta-analysis compared the performance of
Abstract. Cranial cruciate ligament (CrCL) disease/rupture is a highly prevalent orthopaedic disease in dogs and common cause of pain, lameness, and secondary joint osteoarthritis (OA). Previous experiments investigating the role of glutamate receptors (GluR) in arthritic degeneration and pain revealed that OA biomarkers assessing early bone turnover and inflammation, including osteoprotegerin (OPG) and the receptor activator of nuclear factor kappa-B ligand (RANKL) are more likely to be influenced by glutamate signalling. Moreover,
Aims. Tocilizumab, an
Introduction: Activated peri-prosthetic macrophages release pro-inflammatory cytokines, including
There is evidence that fractures heal more rapidly in patients with head injury. We measured the circulating level of
Aims. This study aimed to explore whether serum combined with synovial
Aims: Hormone replacement therapy (HRT) reverses the menopausal decline in bone mineral density (BMD).We investigate if part of this response is through modulation of
Senescent chondrocyte and subchondral osteoclast overburden aggravate inflammatory cytokine and pro-catabolic proteinase overproduction, accelerating extracellular matrix degradation and pain during osteoarthritis (OA). Fibronectin type III domain containing 5 (FNDC5) is found to promote tissue homeostasis and alleviate inflammation. This study aimed to characterize what role Fndc5 may play in chondrocyte aging and OA development. Serum and macroscopically healthy and osteoarthritic cartilage were biopsied from patients with knee OA who received total knee replacement. Murine chondrocytes were transfected with Fndc5 RNAi or cDNA. Mice overexpressing Fndc5 (Fndc5Tg) were operated to have destabilized medial meniscus mediated (DMM) joint injury as an experimental OA model. Cellular senescence was characterized using RT-PCR analysis of p16INK4A, p21CIP1, and p53 expression together with ß-galactosidase activity staining. Articular cartilage damage and synovitis were graded using OARSI scores. Osteophyte formation and mechanical allodynia were quantified using microCT imaging and von Frey filament, respectively. Osteoclast formation was examined using tartrate-resistant acid phosphatase staining. Senescent chondrocyte and subchondral osteoclast overburden together with decreased serum FNDC5 levels were present in human osteoarthritic cartilage. Fndc5 knockdown upregulated senescence program together with increased IL-6, MMP9 and Adamts5 expression, whereas Alcian blue-stained glycosaminoglycan production were inhibited. Forced Fndc5 expression repressed senescence, apoptosis and IL-6 expression, reversing proliferation and extracellular matrix production in inflamed chondrocytes. Fndc5Tg mice showed few OA signs, including articular cartilage erosion, synovitis, osteophyte formation, subchondral plate sclerosis and mechanical allodynia together with decreased IL-6 production and few senescent chondrocytes and subchondral osteoclast formation during DMM-induced joint injury. Mechanistically, Fndc5 reversed histone H3K27me3-mediated IL-6 transcription repression to reduce reactive oxygen species production. Fndc5 loss correlated with OA development. It was indispensable in chondrocyte growth and anabolism. This study sheds light onto the anti-ageing and anti-inflammatory actions of Fndc5 to chondrocytes; and highlights the chondroprotective function of Fndc5 to compromise OA.
The purpose of this study was to evaluate whether
the serum level of interleukin 6 (IL-6) could be used to identify the
persistence of infection after the first stage of a two-stage revision
for periprosthetic joint infection. Between 2010 and 2011, we prospectively studied 55 patients (23
men, 32 women; mean age 69.5 years; 36 to 86) with a periprosthetic
joint infection. Bacteria were identified in two intra-operative
tissue samples during re-implantation in 16 patients. These cases
were classified as representing persistent infection. To calculate a precise cut-off value which could be used in everyday
clinical practice, a 3 x 2 contingency table was constructed and
manually defined. We found that a serum IL-6 ≥ 13 pg/mL can be regarded as indicating
infection: its positive-predictive value is 90.9%. A serum IL-6 ≤ 8
pg/mL can be regarded as indicating an absence of infection: its
negative predictive value is 92.1%. The serum IL-6 level seems to be a reasonable marker for identifying
persistent infection after the first stage of a revision joint arthroplasty
and before attempting re-implantation. Cite this article:
Low bone mass and osteopenia have been described in the axial and peripheral skeleton of patients with adolescent idiopathic scoliosis (AIS). Recently, many studies have shown that gene polymorphism is related to osteoporosis. However, no studies have linked the association between IL6 gene polymorphism and bone mass in AIS. This study examined the association between bone mass and IL6 gene polymorphism in 198 girls with AIS. The polymorphisms of IL6-597 G→A, IL6-572 G→C and IL6-174 G→A and the bone mineral density in the lumbar spine and femoral neck were analysed and compared with their levels in healthy controls. The mean bone mineral density at both sites in patients with AIS was decreased compared with controls (p = 0.0022 and p = 0.0013, respectively). Comparison of genotype frequencies between AIS and healthy controls revealed a statistically significant difference in IL6-572 G→C polymorphism (p = 0.0305). There was a significant association between the IL6-572 G→C polymorphism and bone mineral density in the lumbar spine, with the CC genotype significantly higher with the GC (p = 0.0124) or GG (p = 0.0066) genotypes. These results suggest that the IL6-572 G→C polymorphism is associated with bone mineral density in the lumbar spine in Korean girls with AIS.
Although IL-6 mRNA expression in rat is restricted to the first day post-fracture, the inflammatory phase, the protein has been observed later in the healing process, indicating additional roles. The importance of IL-6 was demonstrated by delayed healing in knockout mice through diminished osteoclast numbers, formation thereof being stimulated by IL-6. The aim of our study was to investigate with which cells this cytokine is associated and when during fracture healing. A closed fracture of the lower right limb was created in rats. The tibia was obtained from six animals at each of 1, 3, 7, 14 and 28 days post-fracture, decalcified and prepared for standard immunohistochemistry with an IL-6-specific polyclonal antibody. The number and types of cells positively stained for IL-6 along the whole length of the periosteal callus on one surface and in the fracture was evaluated. Mostly inflammatory cells were initially stained, becoming virtually absent by day 7 when this phase has normally ended. Within the immediate vicinity of the fracture where endochondrial ossification occurred, staining of chondrocytes was significant (69%) by day 7 when this cell was laying down cartilaginous tissue that was also calcified. Distally to the fracture where direct bone formation occurred through intra-membranous ossification by osteoblasts, staining of these cells was observed, peaking at day 14 (56%). As this bone started to take on the appearance of cortex and surviving embedded osteoblasts differentiated to osteocytes, the latter cells were stained, suggesting a role in remodelling. At the fracture as bone replaced the cartilaginous tissue and union occurred, staining of chondrocytes decreased, whereas local osteoblasts were positive. IL-6 appears to play a role throughout fracture healing, in endochondrial and intra-membranous ossification. The level of staining of each cell type reflected the degree of their activity with respect to production of related tissue.
The study aimed to determine whether the microRNA miR21-5p (MiR21) mediates temporomandibular joint osteoarthritis (TMJ-OA) by targeting growth differentiation factor 5 (Gdf5). TMJ-OA was induced in MiR21 knockout (KO) mice and wild-type (WT) mice by a unilateral anterior crossbite (UAC) procedure. Mouse tissues exhibited histopathological changes, as assessed by: Safranin O, toluidine blue, and immunohistochemistry staining; western blotting (WB); and quantitative real-time polymerase chain reaction (RT-qPCR). Mouse condylar chondrocytes were transfected with a series of MiR21 mimic, MiR21 inhibitor, Gdf5 siRNA (si-GDF5), and flag-GDF5 constructs. The effects of MiR-21 and Gdf5 on the expression of OA related molecules were evaluated by immunofluorescence, alcian blue staining, WB, and RT-qPCR.Aims
Methods
A balanced inflammatory response is important for successful fracture healing. The response of osteoporotic fracture healing is deranged and an altered inflammatory response can be one underlying cause. The objectives of this review were to compare the inflammatory responses between normal and osteoporotic fractures and to examine the potential effects on different healing outcomes. A systematic literature search was conducted with relevant keywords in PubMed, Embase, and Web of Science independently. Original preclinical studies and clinical studies involving the investigation of inflammatory response in fracture healing in ovariectomized (OVX) animals or osteoporotic/elderly patients with available full text and written in English were included. In total, 14 articles were selected. Various inflammatory factors were reported; of those tumour necrosis factor-α (TNF-α) and interleukin (IL)-6 are two commonly studied markers. Preclinical studies showed that OVX animals generally demonstrated higher systemic inflammatory response and poorer healing outcomes compared to normal controls (SHAM). However, it is inconclusive if the local inflammatory response is higher or lower in OVX animals. As for clinical studies, they mainly examine the temporal changes of the inflammatory stage or perform comparison between osteoporotic/fragility fracture patients and normal subjects without fracture. Our review of these studies emphasizes the lack of understanding that inflammation plays in the altered fracture healing response of osteoporotic/elderly patients. Taken together, it is clear that additional studies, preclinical and clinical, are required to dissect the regulatory role of inflammatory response in osteoporotic fracture healing. Cite this article:
Aims. Rheumatoid arthritis (RA), which mainly results from fibroblast-like synoviocyte (FLS) dysfunction, is related to oxidative stress. Advanced oxidation protein products (AOPPs), which are proinflammatory mediators and a novel biomarker of oxidative stress, have been observed to accumulate significantly in the serum of RA patients. Here, we present the first investigation of the effects of AOPPs on RA-FLSs and the signalling pathway involved in AOPP-induced inflammatory responses and invasive behaviour. Methods. We used different concentrations of AOPPs (50 to 200 µg/ml) to treat RA-FLSs. Cell migration and invasion and the expression levels of tumour necrosis factor-alpha (TNF-α),