Objectives. The molecular mechanism of rheumatoid arthritis (RA) remains elusive. We conducted a protein-protein interaction network-based integrative analysis of genome-wide association studies (GWAS) and gene expression profiles of RA. Methods. We first performed a dense search of RA-associated gene modules by integrating a large GWAS meta-analysis dataset (containing 5539 RA patients and 20 169 healthy controls), protein interaction network and gene expression profiles of RA
Adult mice lacking the transcription factor NFAT1 exhibit osteoarthritis (OA). The precise molecular mechanism for NFAT1 deficiency-induced osteoarthritic cartilage degradation remains to be clarified. This study aimed to investigate if NFAT1 protects articular cartilage (AC) against OA by directly regulating the transcription of specific catabolic and anabolic genes in articular chondrocytes. Through a combined approach of gene expression analysis and web-based searching of NFAT1 binding sequences, 25 candidate target genes that displayed aberrant expression in Objectives
Methods
This study aimed to examine the effects of SRT1720, a potent SIRT1 activator, on osteoarthritis (OA) progression using an experimental OA model. Osteoarthritis was surgically induced by destabilization of the medial meniscus in eight-week-old C57BL/6 male mice. SRT1720 was administered intraperitoneally twice a week after surgery. Osteoarthritis progression was evaluated histologically using the Osteoarthritis Research Society International (OARSI) score at four, eight, 12 and 16 weeks. The expression of SIRT1, matrix metalloproteinase 13 (MMP-13), a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), cleaved caspase-3, PARP p85, and acetylated nuclear factor (NF)-κB p65 in cartilage was examined by immunohistochemistry. Synovitis was also evaluated histologically. Primary mouse epiphyseal chondrocytes were treated with SRT1720 in the presence or absence of interleukin 1 beta (IL-1β), and gene expression changes were examined by real-time polymerase chain reaction (PCR).Objectives
Methods
Metabolic syndrome and low-grade systemic inflammation are associated with knee osteoarthritis (OA), but the relationships between these factors and OA in other synovial joints are unclear. The aim of this study was to determine if a high-fat/high-sucrose (HFS) diet results in OA-like joint damage in the shoulders, knees, and hips of rats after induction of obesity, and to identify potential joint-specific risks for OA-like changes. A total of 16 male Sprague-Dawley rats were allocated to either the diet-induced obesity group (DIO, 40% fat, 45% sucrose, n = 9) or a chow control diet (n = 7) for 12 weeks. At sacrifice, histological assessments of the shoulder, hip, and knee joints were performed. Serum inflammatory mediators and body composition were also evaluated. The total Mankin score for each animal was assessed by adding together the individual Modified Mankin scores across all three joints. Linear regression modelling was conducted to evaluate predictive relationships between serum mediators and total joint damage.Objectives
Methods
The role of mechanical stress and transforming growth factor beta 1 (TGF-β1) is important in the initiation and progression of osteoarthritis (OA). However, the underlying molecular mechanisms are not clearly known. In this study, TGF-β1 from osteoclasts and knee joints were analyzed using a co-cultured cell model and an OA rat model, respectively. Five patients with a femoral neck fracture (four female and one male, mean 73.4 years (68 to 79)) were recruited between January 2015 and December 2015. Results showed that TGF-β1 was significantly upregulated in osteoclasts by cyclic loading in a time- and dose-dependent mode. The osteoclasts were subjected to cyclic loading before being co-cultured with chondrocytes for 24 hours.Objectives
Methods
Sustained intra-articular delivery of pharmacological agents is an attractive modality but requires use of a safe carrier that would not induce cartilage damage or fibrosis. Collagen scaffolds are widely available and could be used intra-articularly, but no investigation has looked at the safety of collagen scaffolds within synovial joints. The aim of this study was to determine the safety of collagen scaffold implantation in a validated A total of 96 rabbits were randomly and equally assigned to four different groups: arthrotomy alone; arthrotomy and collagen scaffold placement; contracture surgery; and contracture surgery and collagen scaffold placement. Animals were killed in equal numbers at 72 hours, two weeks, eight weeks, and 24 weeks. Joint contracture was measured, and cartilage and synovial samples underwent histological analysis.Objectives
Materials and Methods
Triamcinolone acetonide (TA) is widely used for the treatment of rotator cuff injury because of its anti-inflammatory properties. However, TA can also produce deleterious effects such as tendon degeneration or rupture. These harmful effects could be prevented by the addition of platelet-rich plasma (PRP), however, the anti-inflammatory and anti-degenerative effects of the combined use of TA and PRP have not yet been made clear. The objective of this study was to determine how the combination of TA and PRP might influence the inflammation and degeneration of the rotator cuff by examining rotator cuff-derived cells induced by interleukin (IL)-1ß. Rotator cuff-derived cells were seeded under inflammatory stimulation conditions (with serum-free medium with 1 ng/ml IL-1ß for three hours), and then cultured in different media: serum-free (control group), serum-free + TA (0.1mg/ml) (TA group), serum-free + 10% PRP (PRP group), and serum-free + TA (0.1mg/ml) + 10% PRP (TA+PRP group). Cell morphology, cell viability, and expression of inflammatory and degenerative mediators were assessed.Objectives
Methods
Ligaments which heal spontaneously have a healing process that
is similar to skin wound healing. Menopause impairs skin wound healing
and may likewise impair ligament healing. Our purpose in this study
was to investigate the effect of surgical menopause on ligament
healing in a rabbit medial collateral ligament model. Surgical menopause was induced with ovariohysterectomy surgery
in adult female rabbits. Ligament injury was created by making a
surgical gap in the midsubstance of the medial collateral ligament.
Ligaments were allowed to heal for six or 14 weeks in the presence
or absence of oestrogen before being compared with uninjured ligaments. Molecular
assessment examined the messenger ribonucleic acid levels for collagens,
proteoglycans, proteinases, hormone receptors, growth factors and
inflammatory mediators. Mechanical assessments examined ligament
laxity, total creep strain and failure stress.Objectives
Methods
Osteoarthritis (OA) is an important cause of
pain, disability and economic loss in humans, and is similarly important in
the horse. Recent knowledge on post-traumatic OA has suggested opportunities
for early intervention, but it is difficult to identify the appropriate
time of these interventions. The horse provides two useful mechanisms
to answer these questions: 1) extensive experience with clinical
OA in horses; and 2) use of a consistently predictable model of
OA that can help study early pathobiological events, define targets
for therapeutic intervention and then test these putative therapies.
This paper summarises the syndromes of clinical OA in horses including
pathogenesis, diagnosis and treatment, and details controlled studies
of various treatment options using an equine model of clinical OA.
Excessive mechanical stress on synovial joints causes osteoarthritis
(OA) and results in the production of prostaglandin E2 (PGE2), a
key molecule in arthritis, by synovial fibroblasts. However, the
relationship between arthritis-related molecules and mechanical
stress is still unclear. The purpose of this study was to examine
the synovial fibroblast response to cyclic mechanical stress using
an Human synovial fibroblasts were cultured on collagen scaffolds
to produce three-dimensional constructs. A cyclic compressive loading
of 40 kPa at 0.5 Hz was applied to the constructs, with or without
the administration of a cyclooxygenase-2 (COX-2) selective inhibitor
or dexamethasone, and then the concentrations of PGE2, interleukin-1β (IL-1β),
tumour necrosis factor-α (TNF-α), IL-6, IL-8 and COX-2 were measured.Objective
Method