1,25(OH)D ameliorates palmitate-induced lipotoxicity in human primary osteoblasts leading to improved viability and function.

Contributing to bone loss with aging is a progressive reduction in osteoblast number and function leading to decreased bone formation. In aging bone, mesenchymal stem cells decrease in number and their differentiation potential into osteoblasts is reduced. Instead, there is a shift towards adipogenic differentiation and increased lipid accumulation in the marrow of osteoporotic bones.

Picolinic Acid, a Catabolite of Tryptophan, Has an Anabolic Effect on Bone In Vivo.

Fractures attributable to osteoporosis have a severe impact on our older population. Reports of side effects with commonly prescribed osteoporosis drugs have led to the investigation of new and safer treatments with novel mechanisms of action. Picolinic acid (PIC), a catabolite of tryptophan, induces in vitro osteogenic differentiation of mesenchymal stem cells.

Rapamycin Affects Palmitate-Induced Lipotoxicity in Osteoblasts by Modulating Apoptosis and Autophagy.

Bone marrow fat infiltration is one of the hallmarks of aging and osteoporotic bones. Marrow adipocytes produce substantial amounts of palmitic acid (PA). PA is toxic to bone-forming osteoblasts in vitro, affecting their differentiation, function, and survival.

Mechanisms of palmitate-induced lipotoxicity in osteocytes.

Background: Lipotoxicity is defined as cellular toxicity observed in the presence of an abnormal accumulation of fat and adipocyte-derived factors in non-fat tissues. Palmitic acid (PA), an abundant fatty acid in the bone marrow and particularly in osteoporotic bones, affects osteoblastogenesis and osteoblast function, decreasing their survival through induction of apoptosis and dysfunctional autophagy. In this study, we hypothesized that PA also has a lipotoxic effect on osteocytes in vitro.

A comparative study of the effect of submicron porous and smooth ultrafine-grained Ti-20Mo surfaces on osteoblast responses.

The surface of an orthopaedic implant plays a crucial role in determining the adsorption of proteins and cell functions. A detailed comparative study has been made of the in vitro osteoblast responses to coarse-grained (grain size: 500 μm), ultrafine-grained (grain size: 100 nm), coarse-porous (pore size: 350 nm), and fine-porous (pore size: 155 nm) surfaces of Ti-20Mo alloy. The purpose was to provide essential experimental data for future design of orthopaedic titanium implants for rapid osseointegration.

Osteochondral repair using an acellular dermal matrix-pilot in vivo study in a rabbit osteochondral defect model.

Unlabelled: The aim of this pilot project was to introduce a novel use of acellular dermal matrix (ADM) in combination with infrapatellar fat pad mesenchymal stromal cells (IPFP-MSCs) to effect repair in a rabbit osteochondral defect model. ADM, in a range of surgical procedures, has been shown to promote remodelling of tissue at the site of implantation. Rabbit-derived ADM (rabADM) was prepared from the skin of donor rabbits.

Chondrogenesis of Human Infrapatellar Fat Pad Stem Cells on Acellular Dermal Matrix.

Acellular dermal matrix (ADM) has been in clinical use for decades in numerous surgical applications. The ability for ADM to promote cellular repopulation, revascularisation and tissue regeneration is well documented. Adipose stem cells have the ability to differentiate into mesenchymal tissue types, including bone and cartilage.

Applying Advanced Imaging Techniques to a Murine Model of Orthotopic Osteosarcoma.

Introduction: Reliable animal models are required to evaluate novel treatments for osteosarcoma. In this study, the aim was to implement advanced imaging techniques in a murine model of orthotopic osteosarcoma to improve disease modeling and the assessment of primary and metastatic disease.

Materials And Methods: Intra-tibial injection of luciferase-tagged OPGR80 murine osteosarcoma cells was performed in Balb/c nude mice.

Combination of agrin and laminin increase acetylcholine receptor clustering and enhance functional neuromuscular junction formation In vitro.

Clustering of acetylcholine receptors (AChR) at the postsynaptic membrane is a crucial step in the development of neuromuscular junctions (NMJ). During development and after denervation, aneural AChR clusters form on the sarcolemma. Recent studies suggest that these receptors are critical for guiding and initiating synaptogenesis.

Osteoclast formation elicited by interleukin-33 stimulation is dependent upon the type of osteoclast progenitor.

Osteoclasts are bone resorbing multinucleated cells (MNCs) derived from macrophage progenitors. IL-33 has been reported to drive osteoclastogenesis independently of receptor activator of NFκB ligand (RANKL) but this remains controversial as later studies did not confirm this. We found IL-33 clearly elicited functional dentine-resorbing osteoclast formation from human adult monocytes.

Bioactive coatings for orthopaedic implants-recent trends in development of implant coatings.

Joint replacement is a major orthopaedic procedure used to treat joint osteoarthritis. Aseptic loosening and infection are the two most significant causes of prosthetic implant failure. The ideal implant should be able to promote osteointegration, deter bacterial adhesion and minimize prosthetic infection.

Chondrogenesis of infrapatellar fat pad derived adipose stem cells in 3D printed chitosan scaffold.

Infrapatellar fat pad adipose stem cells (IPFP-ASCs) have been shown to harbor chondrogenic potential. When combined with 3D polymeric structures, the stem cells provide a source of stem cells to engineer 3D tissues for cartilage repair. In this study, we have shown human IPFP-ASCs seeded onto 3D printed chitosan scaffolds can undergo chondrogenesis using TGFβ3 and BMP6.

Recent advances in nerve tissue engineering.

Nerve injury secondary to trauma, neurological disease or tumor excision presents a challenge for surgical reconstruction. Current practice for nerve repair involves autologous nerve transplantation, which is associated with significant donor-site morbidity and other complications. Previously artificial nerve conduits made from polycaprolactone, polyglycolic acid and collagen were approved by the FDA (USA) for nerve repair.

Differentiation of stem cells from human infrapatellar fat pad: characterization of cells undergoing chondrogenesis.

Hyaline cartilage repair is a significant challenge in orthopedics and current techniques result in formation of fibrocartilage. Human infrapatellar fat pad (hIPFP)-derived mesenchymal stem cells (MSCs) are capable of differentiation into multiple tissue lineages, including cartilage and bone. Chondrogenesis is a crucial part of normal skeletal development but the molecular mechanisms are yet to be completely defined.

In vivo measurement of hippocampal GABAA/cBZR density with [18F]-flumazenil PET for the study of disease progression in an animal model of temporal lobe epilepsy.

Purpose: Imbalance of inhibitory GABAergic neurotransmission has been proposed to play a role in the pathogenesis of temporal lobe epilepsy (TLE). This study aimed to investigate whether [(18)F]-flumazenil ([(18)F]-FMZ) PET could be used to non-invasively characterise GABAA/central benzodiazepine receptor (GABAA/cBZR) density and affinity in vivo in the post-kainic acid status epilepticus (SE) model of TLE.

Methods: Dynamic [(18)F]-FMZ -PET scans using a multi-injection protocol were acquired in four male wistar rats for validation of the partial saturation model (PSM).

18F-flumazenil: a γ-aminobutyric acid A-specific PET radiotracer for the localization of drug-resistant temporal lobe epilepsy.

Unlabelled: Studies report that (11)C-flumazenil (FMZ) PET more specifically localizes the epileptogenic zone in patients with medically refractory focal epilepsy than (18)F-FDG PET. However, practical aspects of (11)C use limit clinical application. We report a phase I/IIa study assessing the clinical use of (18)F-FMZ PET for the localization of the epileptogenic zone in patients with drug-resistant temporal lobe epilepsy (TLE).

Can structural or functional changes following traumatic brain injury in the rat predict epileptic outcome?

Purpose: Posttraumatic epilepsy (PTE) occurs in a proportion of traumatic brain injury (TBI) cases, significantly compounding the disability, and risk of injury and death for sufferers. To date, predictive biomarkers for PTE have not been identified. This study used the lateral fluid percussion injury (LFPI) rat model of TBI to investigate whether structural, functional, and behavioral changes post-TBI relate to the later development of PTE.

Bioengineering of articular cartilage: past, present and future.

The treatment of cartilage defects poses a clinical challenge owing to the lack of intrinsic regenerative capacity of cartilage. The use of tissue engineering techniques to bioengineer articular cartilage is promising and may hold the key to the successful regeneration of cartilage tissue. Natural and synthetic biomaterials have been used to recreate the microarchitecture of articular cartilage through multilayered biomimetic scaffolds.

The osteochondral dilemma: review of current management and future trends.

The management of articular cartilage defects remains challenging and controversial. Hyaline cartilage has limited capacity for self-repair and post-injury cartilage is predominantly replaced by fibrocartilage through healing from the subchondral bone. Fibrocartilage lacks the key properties that characterize hyaline cartilage such as capacity for compression, hydrodynamic permeability and smoothness of the articular surface.

Confounding neurodegenerative effects of manganese for in vivo MR imaging in rat models of brain insults.

Purpose: To examine the long-term consequences of manganese exposure due to the use of manganese-enhanced magnetic resonance imaging (MEMRI) in a model of closed head injury, the fluid-percussion injury (FPI) model.

Materials And Methods: Two groups of adult male Wistar rats (n = 72) were studied with either MEMRI, whereby rats receive MnCl(2) (100 mg/kg intraperitoneally) 24 hours prior to scanning, or standard MRI (sMRI) with no contrast agent. Rats from both groups underwent FPI or sham injury and were longitudinally assessed for 6 months for neurological toxicity using behavioral tests, EEG recording, and MRI scanning.

The molecular pathogenesis of osteosarcoma: a review.

Osteosarcoma is the most common primary malignancy of bone. It arises in bone during periods of rapid growth and primarily affects adolescents and young adults. The 5-year survival rate for osteosarcoma is 60%-70%, with no significant improvements in prognosis since the advent of multiagent chemotherapy.

Quantitative comparison of preparation methodologies for X-ray fluorescence microscopy of brain tissue.

X-ray fluorescence microscopy (XFM) facilitates high-sensitivity quantitative imaging of trace metals at high spatial resolution over large sample areas and can be applied to a diverse range of biological samples. Accurate determination of elemental content from recorded spectra requires proper calibration of the XFM instrument under the relevant operating conditions. Here, we describe the manufacture, characterization, and utilization of multi-element thin-film reference foils for use in calibration of XFM measurements of biological and other specimens.

Therapeutic targeting of osteoclast function and pathways.

Introduction: Osteoclasts are responsible for bone resorption and underlie a number of pathological states in which osteolysis is a feature. Over recent decades our molecular understanding of osteoclast differentiation and activation has expanded significantly, and this has allowed for the development of a number of osteoclast-targeted therapies.

Areas Covered: This review seeks to present the underlying molecular mechanisms of osteoclast differentiation and activity as a basis for understanding our current treatment of osteoporosis and malignant tumors in bone.

Seizure-like thalamocortical rhythms initiate in the deep layers of the cortex in a co-culture model.

The oscillatory rhythms underlying many physiological and pathological states, including absence seizures, require both the thalamus and cortices for full expression. A co-culture preparation combining cortical and thalamic explants provides a unique model for investigating how such oscillations initiate and spread. Here we investigated the dynamics of synchronized thalamocortical activity by simultaneous measurement of field-potential recordings and rapid imaging of Ca(2+) transients by fluorescence methods.