The role of inflammatory cells and their products in tendinopathy is not completely understood.
Objectives. Osteoarthritis (OA) is the most common form of arthritis, affecting approximately 15% of the human population. Recently, increased concentration of nitric oxide in serum and synovial fluid in patients with OA has been observed. However, the exact role of nitric oxide in the initiation of OA has not been elucidated. The aim of the present study was to investigate the role of nitric oxide in innate immune regulation during OA initiation in rats. Methods. Rat OA was induced by performing meniscectomy surgery while cartilage samples were collected 0, 7, and 14 days after surgery. Cartilage cytokine levels were determined by using enzyme-linked immunosorbent assay, while other proteins were assessed by using Western blot. Results. In the time course of the study, nitric oxide was increased seven and 14 days after OA induction.
This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation. In this study, 60 rats were included in a titanium rod implantation model and underwent subsequent guanylate cyclase treatment. Imaging, histology, and biomechanics were used to evaluate the osseointegration of rats in each group. First, the impact of VIT on bone integration in aged rats with iron overload was investigated. Subsequently, VIT was employed to modulate the differentiation of MC3T3-E1 cells and RAW264.7 cells under conditions of iron overload.Aims
Methods
The aim of this study was to investigate the role of miR-126 in the development of osteoarthritis, as well as the potential molecular mechanisms involved, in order to provide a theoretical basis for osteoarthritis treatment and a novel perspective for clinical therapy. Human chondrocyte cell line CHON-001 was administrated by different doses of interleukin (IL)-1β to simulate inflammation. Cell viability, migration, apoptosis, IL-6, IL-8, and tumour necrosis factor (TNF)-α expression, as well as expression of apoptosis-related factors, were measured to assess inflammation. miR-126 expression was measured by quantitative polymerase chain reaction (qPCR). Cells were then transfected with miR-126 inhibitor to assess the effect of miR-126 on IL-1β-injured CHON-001 cells. Expression of B-cell lymphoma 2 (Bcl-2) and the activity of mitogen-activated protein kinase (MAPK) / Jun N-terminal kinase (JNK) signaling pathway were measured by Western blot to explore the underlying mechanism through which miR-126 affects IL-1β-induced inflammation.Objectives
Methods
Platelet-rich plasma (PRP) is being used increasingly often in the clinical setting to treat tendon-related pathologies. Yet the optimal PRP preparations to promote tendon healing in different patient populations are poorly defined. Here, we sought to determine whether increasing the concentration of platelet-derived proteins within a derivative of PRP, platelet lysate (PL), enhances tenocyte proliferation and migration Concentrated PLs from both young (< 50 years) and aged (> 50 years) donors were prepared by exposing pooled PRP to a series of freeze-thaw cycles followed by dilution in plasma, and the levels of several platelet-derived proteins were measured using multiplex immunoassay technology. Human tenocytes were cultured with PLs to simulate a clinically relevant PRP treatment range, and cell growth and migration were assessed using DNA quantitation and gap closure assays, respectively.Objectives
Methods
Recently, high failure rates of metal-on-metal (MOM) hip implants have raised concerns of cobalt toxicity. Adverse reactions occur to cobalt nanoparticles (CoNPs) and cobalt ions (Co2+) during wear of MOM hip implants, but the toxic mechanism is not clear. To evaluate the protective effect of zinc ions (Zn2+), Balb/3T3 mouse fibroblast cells were pretreated with 50 μM Zn2+ for four hours. The cells were then exposed to different concentrations of CoNPs and Co2+ for four hours, 24 hours and 48 hours. The cell viabilities, reactive oxygen species (ROS) levels, and inflammatory cytokines were measured.Objectives
Methods
Rotator cuff tears are among the most frequent upper extremity injuries. Current treatment strategies do not address the poor quality of the muscle and tendon following chronic rotator cuff tears. Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcription factor that activates many genes that are important in skeletal muscle regeneration. HIF-1α is inhibited under normal physiological conditions by the HIF prolyl 4-hydroxylases (PHDs). In this study, we used a pharmacological PHD inhibitor, GSK1120360A, to enhance the activity of HIF-1α following the repair of a chronic cuff tear, and measured muscle fibre contractility, fibrosis, gene expression, and enthesis mechanics. Chronic supraspinatus tears were induced in adult rats, and repaired 28 days later. Rats received 0 mg/kg, 3 mg/kg, or 10 mg/kg GSK1120360A daily. Collagen content, contractility, fibre type distribution and size, the expression of genes involved in fibrosis, lipid accumulation, atrophy and inflammation, and the mechanical properties of the enthesis were then assessed two weeks following surgical repair.Objectives
Methods
Given the function of adiponectin (ADIPOQ) on the inflammatory condition of obesity and osteoarthritis (OA), we hypothesized that the ADIPOQ gene might be a candidate gene for a marker of susceptibility to OA. We systematically screened three tagging polymorphisms (rs182052, rs2082940 and rs6773957) in the ADIPOQ gene, and evaluated the association between the genetic variants and OA risk in a case-controlled study that included 196 OA patients and 442 controls in a northern Chinese population. Genotyping was performed using the Sequenom MassARRAY iPLEX platform.Objectives
Methods
We have undertaken a prospective study in patients with a fracture of the femoral shaft requiring intramedullary nailing to test the hypothesis that the femoral canal could be a potential source of the second hit phenomenon. We determined the local femoral intramedullary and peripheral release of interleukin-6 (IL-6) after fracture and subsequent intramedullary reaming. In all patients, the fracture caused a significant increase in the local femoral concentrations of IL-6 compared to a femoral control group. The concentration of IL-6 in the local femoral environment was significantly higher than in the patients own matched blood samples from their peripheral circulation. The magnitude of the local femoral release of IL-6 after femoral fracture was independent of the injury severity score and whether the fracture was closed or open. In patients who underwent intramedullary reaming of the femoral canal a further significant local release of IL-6 was demonstrated, providing evidence that intramedullary reaming can cause a significant local inflammatory reaction.
Rotator cuff tears are among the most common and debilitating
upper extremity injuries. Chronic cuff tears result in atrophy and
an infiltration of fat into the muscle, a condition commonly referred
to as ‘fatty degeneration’. While stem cell therapies hold promise
for the treatment of cuff tears, a suitable immunodeficient animal
model that could be used to study human or other xenograft-based
therapies for the treatment of rotator cuff injuries had not previously
been identified. A full-thickness, massive supraspinatus and infraspinatus tear
was induced in adult T-cell deficient rats. We hypothesised that,
compared with controls, 28 days after inducing a tear we would observe
a decrease in muscle force production, an accumulation of type IIB
fibres, and an upregulation in the expression of genes involved
with muscle atrophy, fibrosis and inflammation.Objectives
Methods
This systematic review aimed to assess the A systematic search was performed in Pubmed, followed by a two-step selection process. We included Objectives
Methods
Interleukin 18 (IL-18) is a regulatory cytokine that degrades the disc matrix. Bone morphogenetic protein-2 (BMP-2) stimulates synthesis of the disc extracellular matrix. However, the combined effects of BMP-2 and IL-18 on human intervertebral disc degeneration have not previously been reported. The aim of this study was to investigate the effects of the anabolic cytokine BMP-2 and the catabolic cytokine IL-18 on human nucleus pulposus (NP) and annulus fibrosus (AF) cells and, therefore, to identify potential therapeutic and clinical benefits of recombinant human (rh)BMP-2 in intervertebral disc degeneration. Levels of IL-18 were measured in the blood of patients with intervertebral disc degenerative disease and in control patients. Human NP and AF cells were cultured in a NP cell medium and treated with IL-18 or IL-18 plus BMP-2. mRNA levels of target genes were measured by real-time polymerase chain reaction, and protein levels of aggrecan, type II collagen, SOX6, and matrix metalloproteinase 13 (MMP13) were assessed by western blot analysis.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
The cytotoxicity induced by cobalt ions (Co2+) and cobalt nanoparticles (Co-NPs) which released following the insertion of a total hip prosthesis, has been reported. However, little is known about the underlying mechanisms. In this study, we investigate the toxic effect of Co2+ and Co-NPs on liver cells, and explain further the potential mechanisms. Co-NPs were characterised for size, shape, elemental analysis, and hydrodynamic diameter, and were assessed by Transmission Electron Microscope, Scanning Electron Microscope, Energy Dispersive X-ray Spectroscopy and Dynamic Light Scattering. BRL-3A cells were used in this study. Cytotoxicity was evaluated by MTT and lactate dehydrogenase release assay. In order to clarify the potential mechanisms, reactive oxygen species, Bax/Bcl-2 mRNA expression, IL-8 mRNA expression and DNA damage were assessed on BRL-3A cells after Co2+ or Co-NPs treatment.Objectives
Methods
Post-traumatic arthritis is a frequent consequence of articular fracture. The mechanisms leading to its development after such injuries have not been clearly delineated. A potential contributing factor is decreased viability of the articular chondrocytes. The object of this study was to characterise the regional variation in the viability of chondrocytes following joint trauma. A total of 29 osteochondral fragments from traumatic injuries to joints that could not be used in articular reconstruction were analysed for cell viability using the fluorescence live/dead assay and for apoptosis employing the TUNEL assay, and compared with cadaver control fragments. Chondrocyte death and apoptosis were significantly greater along the edge of the fracture and in the superficial zone of the osteochondral fragments. The middle and deep zones demonstrated significantly higher viability of the chondrocytes. These findings indicate the presence of both necrotic and apoptotic chondrocytes after joint injury and may provide further insight into the role of chondrocyte death in post-traumatic arthritis.
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
The establishment of a suitable animal model of repair of the rotator cuff is difficult since the presence of a true rotator cuff anatomically appears to be restricted almost exclusively to advanced primates. Our observational study describes the healing process after repair of the cuff in a primate model. Lesions were prepared and repaired in eight ‘middle-aged’ baboons. Two each were killed at four, eight, 12 and 15 weeks post-operatively. The bone-tendon repair zones were assessed macroscopically and histologically. Healing of the baboon supraspinatus involved a sequence of stages resulting in the reestablishment of the bone-tendon junction. It was not uniform and occurred more rapidly at the sites of suture fixation than between them. Four weeks after repair the bone-tendon healing was immature. Whereas macroscopically the repair appeared to be healed at eight weeks, the Sharpey fibres holding the repair together did not appear in any considerable number before 12 weeks. By 15 weeks, the bone-tendon junction was almost, but not quite mature. Our results support the use of a post-operative rehabilitation programme in man which protects the surgical repair for at least 12 to 15 weeks in order to allow maturation of tendon-to-bone healing.
We stably transfected early passage chondrocytes with an anti-apoptotic Bcl-2 gene We conclude that NO-induced chondrocyte death involves a mechanism which appears to be subject to regulation by an anti-apoptotic Bcl-2 gene. Therefore, Bcl-2 gene therapy may prove to be of therapeutic value in protecting human articular chondrocytes.
We have evaluated the effect of the short-term administration of low therapeutic doses of modern COX-2 inhibitors on the healing of fractures. A total of 40 adult male New Zealand rabbits were divided into five groups. A mid-diaphyseal osteotomy of the right ulna was performed and either normal saline, prednisolone, indometacin, meloxicam or rofecoxib was administered for five days. Radiological, biomechanical and histomorphometric evaluation was performed at six weeks. In the group in which the highly selective anti-COX-2 agent, rofecoxib, was used the incidence of radiologically-incomplete union was similar to that in the control group. All the biomechanical parameters were statistically significantly lower in both the prednisolone and indometacin (p = 0.01) and in the meloxicam (p = 0.04) groups compared with the control group. Only the fracture load values were found to be statistically significantly lower (p = 0.05) in the rofecoxib group. Histomorphometric parameters were adversely affected in all groups with the specimens of the rofecoxib group showing the least negative effect. Our findings indicated that the short-term administration of low therapeutic doses of a highly selective COX-2 inhibitor had a minor negative effect on bone healing.
