Ubiquitin E3 ligase-mediated protein degradation regulates osteoblast function. Itch, an E3 ligase, affects numerous cell functions by regulating ubiquitination and proteasomal degradation of related proteins. However, the Itch-related cellular and molecular mechanisms by which osteoblast differentiation and function are elevated during bone fracture repair are as yet unknown. We examined the expression levels of E3 ligases and NF-κB members in callus samples during bone fracture repair by quantitative polymerase chain reaction (qPCR) and the total amount of ubiquitinated proteins by Western blot analysis in wild-type (WT) mice. The expression levels of osteoblast-associated genes in fracture callus from Itch knockout (KO) mice and their WT littermates were examined by qPCR. The effect of NF-κB on Itch expression in C2C12 osteoblast cells was determined by a chromatin immunoprecipitation (ChIP) assay.Objectives
Methods
The objectives of this study were: 1) to examine osteophyte formation, subchondral bone advance, and bone marrow lesions (BMLs) in osteoarthritis (OA)-prone Hartley guinea pigs; and 2) to assess the disease-modifying activity of an orally administered phosphocitrate ‘analogue’, Carolinas Molecule-01 (CM-01). Young Hartley guinea pigs were divided into two groups. The first group (n = 12) had drinking water and the second group (n = 9) had drinking water containing CM-01. Three guinea pigs in each group were euthanized at age six, 12, and 18 months, respectively. Three guinea pigs in the first group were euthanized aged three months as baseline control. Radiological, histological, and immunochemical examinations were performed to assess cartilage degeneration, osteophyte formation, subchondral bone advance, BMLs, and the levels of matrix metalloproteinse-13 (MMP13) protein expression in the knee joints of hind limbs.Objectives
Methods
The aims of this study were to increase the diagnostic accuracy
of the analysis of synovial fluid in the differentiation of prosthetic
joint infection (PJI) by the addition of inexpensive biomarkers
such as the levels of C-reactive protein (CRP), adenosine deaminase
(ADA), alpha-2-macrogloblulin (α2M) and procalcitonin. Between January 2013 and December 2015, synovial fluid and removed
implants were requested from 143 revision total joint arthroplasties.
A total of 55 patients met inclusion criteria of the receipt of
sufficient synovial fluid, tissue samples and removed implants for
analysis. The diagnosis of PJI followed the definition from a recent International
Consensus Meeting to create two groups of patients; septic and aseptic.
Using receiver operating characteristic curves we determined the
cutoff values and diagnostic accuracy for each marker.Aims
Patients and Methods
Intermittently administered parathyroid hormone (PTH 1-34) has been shown to promote bone formation in both human and animal studies. The hormone and its analogues stimulate both bone formation and resorption, and as such at low doses are now in clinical use for the treatment of severe osteoporosis. By varying the duration of exposure, parathyroid hormone can modulate genes leading to increased bone formation within a so-called ‘anabolic window’. The osteogenic mechanisms involved are multiple, affecting the stimulation of osteoprogenitor cells, osteoblasts, osteocytes and the stem cell niche, and ultimately leading to increased osteoblast activation, reduced osteoblast apoptosis, upregulation of Wnt/β-catenin signalling, increased stem cell mobilisation, and mediation of the RANKL/OPG pathway. Ongoing investigation into their effect on bone formation through ‘coupled’ and ‘uncoupled’ mechanisms further underlines the impact of intermittent PTH on both cortical and cancellous bone. Given the principally catabolic actions of continuous PTH, this article reviews the skeletal actions of intermittent PTH 1-34 and the mechanisms underlying its effect.
The aim of this study was to examine the efficacy and safety
of multiple boluses of intravenous (IV) tranexamic acid (TXA) on
the hidden blood loss (HBL) and inflammatory response following
primary total hip arthroplasty (THA). A total of 150 patients were allocated randomly to receive a
single bolus of 20 mg/kg IV TXA before the incision (group A), a
single bolus followed by a second bolus of 1 g IV-TXA three hours
later (group B) or a single bolus followed by two boluses of 1 g
IV-TXA three and six hours later (group C). All patients were treated
using a standard peri-operative enhanced recovery protocol. Primary
outcomes were HBL and the level of haemoglobin (Hb) as well as the
levels of C-reactive protein (CRP) and interleukin-6 (IL-6) as markers
of inflammation. Secondary outcomes included the length of stay
in hospital and the incidence of venous thromboembolism (VTE).Aims
Patients 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
The aims of this study were to evaluate the clinical and radiological
outcomes of instrumented posterolateral fusion (PLF) performed in
patients with rheumatoid arthritis (RA). A total of 40 patients with RA and 134 patients without RA underwent
instrumented PLF for spinal stenosis between January 2003 and December
2011. The two groups were matched for age, gender, bone mineral
density, the history of smoking and diabetes, and number of fusion
segments. The clinical outcomes measures included the visual analogue scale
(VAS) and the Korean Oswestry Disability Index (KODI), scored before
surgery, one year and two years after surgery. Radiological outcomes
were evaluated for problems of fixation, nonunion, and adjacent
segment disease (ASD). The mean follow-up was 36.4 months in the RA
group and 39.1 months in the non-RA group.Aims
Methods
Abnormal wear of cobalt-containing metal-on-metal
joints is associated with inflammatory pseudotumours. Cobalt ions
activate human toll-like receptor 4 (TLR4), which normally responds
to bacterial lipopolysaccharide (LPS) in sepsis. Activation of TLR4
by LPS increases the expression of chemokines IL-8 and CXCL10, which
recruit leukocytes and activated T-cells, respectively. This study
was designed to determine whether cobalt induces a similar inflammatory
response to LPS by promoting the expression of IL-8 and CXCL10.
A human monocytic cell line, derived from acute monocytic leukaemia,
was treated with cobalt ions and expression of IL-8 and CXCL10 measured at
mRNA and protein levels. Cobalt-treated macrophages showed a 60-fold
increase in IL-8 mRNA, and an eightfold increase in production of
the mature chemokine (both p <
0.001); expression of the CXCL10
gene and protein was also significantly increased by cobalt (both
p <
0.001). Experiments were also performed in the presence of
CLI-095, a TLR4-specific antagonist which abrogated the cobalt-mediated
increase in IL-8 and CXCL10 expression. These findings suggest that cobalt ions induce inflammation similar
to that observed during sepsis by the simultaneous activation of
two TLR4-mediated signalling pathways. These pathways result in
increased production of IL-8 and CXCL10, and may be implicated in
pseudotumour formation following metal-on-metal replacement. Cite this article:
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
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
The purpose of this study was to evaluate the
expression of acid-sensing ion channels (ASICs) in the capsule and synovial
fluid of patients with frozen shoulder. Capsular tissue and synovial
fluid were obtained from 18 patients with idiopathic frozen shoulder
(FS group) and 18 patients with instability of the shoulder (control
group). The expressions of ASIC1, ASIC2, and ASIC3 in the capsule
were determined using the reverse transcriptase-polymerase chain
reaction, immunoblot analysis, and immunohistochemistry (IHC). The
concentrations in synovial fluid were evaluated using an enzyme-linked
immunosorbent assay. The mRNA expression of ASIC1, ASIC2 and ASIC3 in the capsule
were significantly increased in the FS group compared with the control
group. The protein levels of these three ASICs were also increased.
The increased expressions were confirmed by IHC. Of the ASICs, ASIC3
showed the greatest increase in both mRNA and levels of expression
compared with the control group. The levels of ASIC1 and ASIC3 in
synovial fluid were significantly increased in the FS group. This study suggests that ASICs may play a role as mediators of
inflammatory pain and be involved in the pathogenesis of frozen
shoulder. Cite this article:
The aim of this study was to investigate the effect of granulocyte-colony stimulating factor (G-CSF) on mesenchymal stem cell (MSC) proliferation MSCs from rabbits were cultured in a control medium and medium with G-CSF (low-dose: 4 μg, high-dose: 40 μg). At one, three, and five days after culturing, cells were counted. Differential potential of cultured cells were examined by stimulating them with a osteogenic, adipogenic and chondrogenic medium. A total of 30 rabbits were divided into three groups. The low-dose group (n = 10) received 10 μg/kg of G-CSF daily, the high-dose group (n = 10) received 50 μg/kg daily by subcutaneous injection for three days prior to creating cartilage defects. The control group (n = 10) was administered saline for three days. At 48 hours after the first injection, a 5.2 mm diameter cylindrical osteochondral defect was created in the femoral trochlea. At four and 12 weeks post-operatively, repaired tissue was evaluated macroscopically and microscopically.Objectives
Methods
The present study describes a novel technique for revitalising allogenic intrasynovial tendons by combining cell-based therapy and mechanical stimulation in an Specifically, canine flexor digitorum profundus tendons were used for this study and were divided into the following groups: (1) untreated, unprocessed normal tendon; (2) decellularised tendon; (3) bone marrow stromal cell (BMSC)-seeded tendon; and (4) BMSC-seeded and cyclically stretched tendon. Lateral slits were introduced on the tendon to facilitate cell seeding. Tendons from all four study groups were distracted by a servohydraulic testing machine. Tensile force and displacement data were continuously recorded at a sample rate of 20 Hz until 200 Newton of force was reached. Before testing, the cross-sectional dimensions of each tendon were measured with a digital caliper. Young’s modulus was calculated from the slope of the linear region of the stress-strain curve. The BMSCs were labeled for histological and cell viability evaluation on the decellularized tendon scaffold under a confocal microscope. Gene expression levels of selected extracellular matrix tendon growth factor genes were measured. Results were reported as mean ± SD and data was analyzed with one-way ANOVAs followed by Tukey’s post hoc multiple-comparison test.Objectives
Methods
The purpose of our study is to summarise the current scientific
findings regarding the impact of obesity on total hip arthroplasty
(THA); specifically the influence of obesity on the timing of THA,
incidence of complications, and effect on clinical and functional
outcomes. We performed a systematic review that was compliant with the
Preferred Reporting Items for Systematic Reviews and Meta-Analyses
guidelines to identify prospective studies from the PubMed/Medline,
Embase, and Cochrane Library databases that evaluated primary THA
in obese (body mass index (BMI) ≥ 30 kg/m2) patients.Aims
Materials and 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
We investigated the effects on fracture healing of two up-regulators of inducible nitric oxide synthase (iNOS) in a rat model of an open femoral osteotomy: tadalafil, a phosphodiesterase inhibitor, and the recently reported nutraceutical, COMB-4 (consisting of L-citrulline, Paullinia cupana, ginger and muira puama), given orally for either 14 or 42 days. Unilateral femoral osteotomies were created in 58 male rats and fixed with an intramedullary compression nail. Rats were treated daily either with vehicle, tadalafil or COMB-4. Biomechanical testing of the healed fracture was performed on day 42. The volume, mineral content and bone density of the callus were measured by quantitative CT on days 14 and 42. Expression of iNOS was measured by immunohistochemistry.Objectives
Materials and Methods
