Recent studies have shown that systemic injection of rapamycin can prevent the development of osteoarthritis (OA)-like changes in human chondrocytes and reduce the severity of experimental OA. However, the systemic injection of rapamycin leads to many side effects. The purpose of this study was to determine the effects of intra-articular injection of Torin 1, which as a specific inhibitor of mTOR which can cause induction of autophagy, is similar to rapamycin, on articular cartilage degeneration in a rabbit osteoarthritis model and to investigate the mechanism of Torin 1’s effects on experimental OA. Collagenase (type II) was injected twice into both knees of three-month-old rabbits to induce OA, combined with two intra–articular injections of Torin 1 (400 nM). Degeneration of articular cartilage was evaluated by histology using the Mankin scoring system at eight weeks after injection. Chondrocyte degeneration and autophagosomes were observed by transmission electron microscopy. Matrix metallopeptidase-13 (MMP-13) and vascular endothelial growth factor (VEGF) expression were analysed by quantitative RT-PCR (qPCR).Beclin-1 and light chain 3 (LC3) expression were examined by Western blotting.Objectives
Methods
Construction of a functional skeleton is accomplished
through co-ordination of the developmental processes of chondrogenesis,
osteogenesis, and synovial joint formation. Infants whose movement Cite this article:
To investigate the appropriate dose and interval for the administration
of triamcinolone acetonide (TA) in treating tendinopathy to avoid
adverse effects such as tendon degeneration and rupture. Human rotator cuff-derived cells were cultured using three media:
regular medium (control), regular medium with 0.1 mg/mL of TA (low
TA group), and with 1.0 mg/mL of TA (high TA group). The cell morphology,
apoptosis, and viability were assessed at designated time points.Objectives
Methods
The August 2014 Research Roundup360 looks at: Antibiotic loaded ceramic of use in osteomyelitis; fibronectin implicated in cartilage degeneration; Zinc Chloride accelerates fracture healing in rats; advertisements and false claims; Net Promoter Score: substance or rhetoric?; aspirin for venous thromboembolism prophylaxis and dissection, stress and the soul.
This animal study compares different methods
of performing an osteotomy, including using an Erbium-doped Yttrium
Aluminum Garnet laser, histologically, radiologically and biomechanically.
A total of 24 New Zealand rabbits were divided into four groups
(Group I: multihole-drilling; Group II: Gigli saw; Group III: electrical
saw blade and Group IV: laser). A proximal transverse diaphyseal
osteotomy was performed on the right tibias of the rabbits after the
application of a circular external fixator. The rabbits were killed
six weeks after the procedure, the operated tibias were resected
and radiographs taken. The specimens were tested biomechanically using three-point bending
forces, and four tibias from each group were examined histologically.
Outcome parameters were the biomechanical stability of the tibias
as assessed by the failure to load and radiographic and histological
examination of the osteotomy site. The osteotomies healed in all specimens both radiographically
and histologically. The differences in the mean radiographic (p
= 0.568) and histological (p = 0.71) scores, and in the mean failure
loads (p = 0.180) were not statistically significant between the
groups. Different methods of performing an osteotomy give similar quality
of union. The laser osteotomy, which is not widely used in orthopaedics
is an alternative to the current methods. Cite this article:
Fracture repair occurs by two broad mechanisms:
direct healing, and indirect healing with callus formation. The effects
of bisphosphonates on fracture repair have been assessed only in
models of indirect fracture healing. A rodent model of rigid compression plate fixation of a standardised
tibial osteotomy was used. Ten skeletally mature Sprague–Dawley
rats received daily subcutaneous injections of 1 µg/kg ibandronate
(IBAN) and ten control rats received saline (control). Three weeks
later a tibial osteotomy was rigidly fixed with compression plating.
Six weeks later the animals were killed. Fracture repair was assessed
with mechanical testing, radiographs and histology. The mean stress at failure in a four-point bending test was significantly
lower in the IBAN group compared with controls (8.69 Nmm-2 ( Bisphosphonate treatment in a therapeutic dose, as used for risk
reduction in fragility fractures, had an inhibitory effect on direct
fracture healing. We propose that bisphosphonate therapy not be
commenced until after the fracture has united if the fracture has
been rigidly fixed and is undergoing direct osteonal healing. Cite this article:
The biomembrane (induced membrane) formed around polymethylmethacrylate (PMMA) spacers has value in clinical applications for bone defect reconstruction. Few studies have evaluated its cellular, molecular or stem cell features. Our objective was to characterise induced membrane morphology, molecular features and osteogenic stem cell characteristics. Following Institutional Review Board approval, biomembrane specimens were obtained from 12 patient surgeries for management of segmental bony defects (mean patient age 40.7 years, standard deviation 14.4). Biomembranes from nine tibias and three femurs were processed for morphologic, molecular or stem cell analyses. Gene expression was determined using the Affymetrix GeneChip Operating Software (GCOS). Molecular analyses compared biomembrane gene expression patterns with a mineralising osteoblast culture, and gene expression in specimens with longer spacer duration (> 12 weeks) with specimens with shorter durations. Statistical analyses used the unpaired student Objectives
Methods
Electromagnetic fields (EMF) are widely used in musculoskeletal
disorders. There are indications that EMF might also be effective
in the treatment of osteoporosis. To justify clinical follow-up
experiments, we examined the effects of EMF on bone micro-architectural
changes in osteoporotic and healthy rats. Moreover, we tested the
effects of EMF on fracture healing. EMF (20 Gauss) was examined in rats (aged 20 weeks), which underwent
an ovariectomy (OVX; n = 8) or sham-ovariectomy (sham-OVX; n = 8).
As a putative positive control, all rats received bilateral fibular
osteotomies to examine the effects on fracture healing. Treatment
was applied to one proximal lower leg (three hours a day, five days
a week); the lower leg was not treated and served as a control.
Bone architectural changes of the proximal tibia and bone formation
around the osteotomy were evaluated using Objectives
Methods
Extracorporeal irradiation of an excised tumour-bearing
segment of bone followed by its re-implantation is a technique used
in bone sarcoma surgery for limb salvage when the bone is of reasonable
quality. There is no agreement among previous studies about the
dose of irradiation to be given: up to 300 Gy have been used. We investigated the influence of extracorporeal irradiation on
the elastic and viscoelastic properties of bone. Bone was harvested
from mature cattle and subdivided into 13 groups: 12 were exposed
to increasing levels of irradiation: one was not and was used as
a control. The specimens, once irradiated, underwent mechanical
testing in saline at 37°C. The mechanical properties of each group, including Young’s modulus,
storage modulus and loss modulus, were determined experimentally
and compared with the control group. There were insignificant changes in all of these mechanical properties
with an increasing level of irradiation. We conclude that the overall mechanical effect of high levels
of extracorporeal irradiation (300 Gy) on bone is negligible. Consequently
the dose can be maximised to reduce the risk of local tumour recurrence. Cite this article:
Cartilage repair in terms of replacement, or
regeneration of damaged or diseased articular cartilage with functional tissue,
is the ‘holy grail’ of joint surgery. A wide spectrum of strategies
for cartilage repair currently exists and several of these techniques
have been reported to be associated with successful clinical outcomes
for appropriately selected indications. However, based on respective
advantages, disadvantages, and limitations, no single strategy, or
even combination of strategies, provides surgeons with viable options
for attaining successful long-term outcomes in the majority of patients.
As such, development of novel techniques and optimisation of current techniques
need to be, and are, the focus of a great deal of research from
the basic science level to clinical trials. Translational research
that bridges scientific discoveries to clinical application involves
the use of animal models in order to assess safety and efficacy
for regulatory approval for human use. This review article provides
an overview of animal models for cartilage repair. Cite this article:
The subject of central nervous system damage includes a wide variety of problems, from the slow selective ‘picking off’ of characteristic sub-populations of neurons typical of neurodegenerative diseases, to the wholesale destruction of areas of brain and spinal cord seen in traumatic injury and stroke. Experimental repair strategies are diverse and the type of pathology dictates which approach will be appropriate. Damage may be to grey matter (loss of neurons), white matter (cutting of axons, leaving neurons otherwise intact, at least initially) or both. This review will consider four possible forms of treatment for repair of the human central nervous system.
The April 2015 Research Roundup360 looks at: MCID in grip strength and distal radial fracture; Experiencing rehab in a trial setting; Electrical stimulation and nerve recovery; Molecular diagnosis of TB?; Acetabular orientation: component and arthritis; Analgesia after knee arthroplasty; Bisphosphonate-associated femoral fractures
Heterotopic ossification (HO) is perhaps the
single most significant obstacle to independence, functional mobility, and
return to duty for combat-injured veterans of Operation Enduring
Freedom and Operation Iraqi Freedom. Recent research into the cause(s)
of HO has been driven by a markedly higher prevalence seen in these
wounded warriors than encountered in previous wars or following
civilian trauma. To that end, research in both civilian and military
laboratories continues to shed light onto the complex mechanisms
behind HO formation, including systemic and wound specific factors,
cell lineage, and neurogenic inflammation. Of particular interest,
non-invasive
Injury to the anterior cruciate ligament (ACL)
is one of the most devastating and frequent injuries of the knee. Surgical
reconstruction is the current standard of care for treatment of
ACL injuries in active patients. The widespread adoption of ACL
reconstruction over primary repair was based on early perception
of the limited healing capacity of the ACL. Although the majority
of ACL reconstruction surgeries successfully restore gross joint stability,
post-traumatic osteoarthritis is commonplace following these injuries,
even with ACL reconstruction. The development of new techniques
to limit the long-term clinical sequelae associated with ACL reconstruction
has been the main focus of research over the past decades. The improved
knowledge of healing, along with recent advances in tissue engineering
and regenerative medicine, has resulted in the discovery of novel
biologically augmented ACL-repair techniques that have satisfactory
outcomes in preclinical studies. This instructional review provides
a summary of the latest advances made in ACL repair. Cite this article:
The June 2012 Research Roundup360 looks at: platelet-rich plasma; ageing, bone and mesenchymal stem cells; cytokines and the herniated intervertebral disc; ulcerative colitis, Crohn’s disease and anti-inflammatories; the effect of NSAIDs on bone healing; osteoporosis of the fractured hip; herbal medicine and recovery after acute muscle injury; and ultrasound and the time to fracture union.
The treatment of osteochondral lesions and osteoarthritis
remains an ongoing clinical challenge in orthopaedics. This review
examines the current research in the fields of cartilage regeneration,
osteochondral defect treatment, and biological joint resurfacing, and
reports on the results of clinical and pre-clinical studies. We
also report on novel treatment strategies and discuss their potential
promise or pitfalls. Current focus involves the use of a scaffold
providing mechanical support with the addition of chondrocytes or mesenchymal
stem cells (MSCs), or the use of cell homing to differentiate the
organism’s own endogenous cell sources into cartilage. This method
is usually performed with scaffolds that have been coated with a
chemotactic agent or with structures that support the sustained
release of growth factors or other chondroinductive agents. We also
discuss unique methods and designs for cell homing and scaffold
production, and improvements in biological joint resurfacing. There
have been a number of exciting new studies and techniques developed
that aim to repair or restore osteochondral lesions and to treat
larger defects or the entire articular surface. The concept of a
biological total joint replacement appears to have much potential. Cite this article:
This paper reviews the current literature concerning the main clinical factors which can impair the healing of fractures and makes recommendations on avoiding or minimising these in order to optimise the outcome for patients. The clinical implications are described.
Peri-tendinous injection of local anaesthetic,
both alone and in combination with corticosteroids, is commonly performed
in the treatment of tendinopathies. Previous studies have shown
that local anaesthetics and corticosteroids are chondrotoxic, but
their effect on tenocytes remains unknown. We compared the effects
of lidocaine and ropivacaine, alone or combined with dexamethasone,
on the viability of cultured bovine tenocytes. Tenocytes were exposed
to ten different conditions: 1) normal saline; 2) 1% lidocaine;
3) 2% lidocaine; 4) 0.2% ropivacaine; 5) 0.5% ropivacaine; 6) dexamethasone
(dex); 7) 1% lidocaine+dex; 8) 2% lidocaine+dex; 9) 0.2% ropivacaine+dex;
and 10) 0.5% ropivacaine+dex, for 30 minutes. After a 24-hour recovery
period, the viability of the tenocytes was quantified using the
CellTiter-Glo viability assay and fluorescence-activated cell sorting
(FACS) for live/dead cell counts. A 30-minute exposure to lidocaine
alone was significantly toxic to the tenocytes in a dose-dependent
manner, but a 30-minute exposure to ropivacaine or dexamethasone
alone was not significantly toxic. Dexamethasone potentiated ropivacaine tenocyte toxicity at higher
doses of ropivacaine, but did not potentiate lidocaine tenocyte
toxicity. As seen in other cell types, lidocaine has a dose-dependent
toxicity to tenocytes but ropivacaine is not significantly toxic.
Although dexamethasone alone is not toxic, its combination with
0.5% ropivacaine significantly increased its toxicity to tenocytes.
These findings might be relevant to clinical practice and warrant
further investigation.
The December 2014 Spine Roundup360 looks at: surgeon outcomes; complications and scoliosis surgery; is sequestrectomy enough in lumbar disc prolapse?; predicting outcomes in lumbar disc herniation; sympathectomy has a direct effect on the dorsal root ganglion; and distal extensions of fusion in adolescent idiopathic scoliosis.
In order to clarify the role of cytokines in the remodelling of the grafted tendon for ligament reconstruction we compared the responses to interleukin (IL)-1β, platelet-derived growth factor (PDGF)-BB and transforming growth factor (TGF)-β1 of extrinsic fibroblasts infiltrating the frozen-thawed patellar tendon in rats with that of the normal tendon fibroblasts, in regard to the gene expression of matrix metalloproteinase (MMP)-13, using Northern blot analysis. We also examined, immunohistologically, the local expression of IL-1β, PDGF-BB, and TGF-β1 in fibroblasts infiltrating the frozen-thawed patellar tendon. Northern blot analysis showed that fibroblasts derived from the patellar tendon six weeks after the freeze-thaw procedure