A5081859721- Bone Metabolism and Diseases
- Bone health and treatments
- Bone Tissue Engineering Materials
- Cannabis and Cannabinoid Research
- Tendon Structure and Treatment
- Cancer-related Molecular Pathways
- Biochemical effects in animals
- Dental Implant Techniques and Outcomes
- Periodontal Regeneration and Treatments
- Metabolism, Diabetes, and Cancer
- Shoulder Injury and Treatment
- NF-κB Signaling Pathways
- Sports injuries and prevention
- Nerve Injury and Rehabilitation
- Diet and metabolism studies
- Reconstructive Surgery and Microvascular Techniques
- Natural Compounds in Disease Treatment
- TGF-β signaling in diseases
- Cancer Treatment and Pharmacology
- Neuroscience and Neuropharmacology Research
- Osteoarthritis Treatment and Mechanisms
- Erythrocyte Function and Pathophysiology
- Bone health and osteoporosis research
- Protein Kinase Regulation and GTPase Signaling
- Pharmacological Effects and Toxicity Studies
Perron Institute for Neurological and Translational Science
2021-2024
The University of Western Australia
2012-2024
University of Liverpool
2017
University of Edinburgh
2008-2011
Western General Hospital
2008-2011
Institute of Genetics and Cancer
2009-2011
The endocannabinoid system has recently been shown to play a role in the regulation of bone metabolism. type 2 cannabinoid receptor (CB2) reported regulate mass, but conflicting results have with regard its effects on resorption and osteoclast function. Here we investigated that CB2 plays regulating mass function using combination pharmacological genetic approaches. CB2-selective antagonist/inverse agonist AM630 inhibited formation activity vitro, whereas agonists JWH133 HU308 stimulated...
Mutations of SQSTM1 occur in about10% patients with Paget's disease bone (PDB), but it is unclear whether they play a causal role or regulate susceptibility to an environmental trigger. Here we show that mice proline leucine mutation at codon 394 mouse sqstm1 (P394L), equivalent the P392L humans, develop disorder remarkable similarity PDB. The P394L mutant developed focal lesions increasing age and by 12 months, 14/18 (77%) heterozygotes 20/21 (95%) homozygotes had lesions, compared 0/18...
Identification of functional programmable mechanical stimulation (PMS) on tendon not only provides the insight homeostasis under physical/pathological condition, but also guides a better engineering strategy for regeneration. The aims study are to design bioreactor system with PMS mimic in vivo loading conditions, and define impact different cyclic tensile strain tendon. Rabbit Achilles tendons were loaded with/without (0.25 Hz 8 h/day, 0-9% 6 days). Tendons without lost its structure...
Abstract The NF-κB signaling pathway is known to play an important role in the regulation of osteoclastic bone resorption and cancer cell growth. Previous studies have shown that genetic inactivation IκB kinase (IKK), a key component signaling, inhibits osteoclastogenesis, but effects pharmacologic IKK inhibitors on osteolytic metastasis are unknown. Here, we studied celastrol, BMS-345541, parthenolide, wedelolactone proliferation migration W256 cells vitro destruction vivo. All compounds...
The type 2 cannabinoid receptor (CB2) has been reported to regulate bone mass and turnover but the mechanisms responsible are incompletely understood. In this study we investigated role that CB2 pathway plays in metabolism using a combination of genetic pharmacological approaches. Bone were normal young mice with targeted inactivation (CB2−/−), by 12 months age, they had developed high-turnover osteoporosis relative uncoupling resorption from formation. Primary osteoblasts CB2−/− reduced...
Micro-CT analysis has become the standard method for assessing bone volume and architecture in small animals. However, micro-CT does not allow assessment of turnover parameters such as formation rate osteoclast (OC) number surface. For these crucial variables histomorphometric is still an essential technique. Histomorphometry however, time consuming and, especially mouse bones, OCs can be difficult to detect. The main purpose this study was develop validate a relatively easy rapid measure...
Treatment of cortical bone defects is a clinical challenge. Guided regeneration (GBR), commonly used in oral and maxillofacial dental surgery, may show promise for orthopedic applications repair defects. However, limitation the use GBR lack an ideal scaffold that provides sufficient mechanical support to bridge with minimal interference process. We have developed new collagen membrane, CelGro™, GBR. report material characterization CelGro evaluate performance translational preclinical...
Alveolar bone loss is a common problem that affects dental implant placement. A barrier between the substitute and gingiva can prevent fibro-tissue ingrowth, bacterial infection induce formation key factor in improving success of alveolar ridge reconstruction. This study aims to develop bioactive collagen material for guided regeneration, coupled with anti-bacterial anti-inflammatory properties. We have evaluated two silver coating methods found controllable precise achieved by sonication...
Abstract Osteoclasts are giant bone-digesting cells that harbor specialized lysosome-related organelles termed secretory lysosomes (SLs). SLs store cathepsin K and serve as a membrane precursor to the ruffled border, osteoclast’s ‘resorptive apparatus’. Yet, molecular composition spatiotemporal organization of remains incompletely understood. Here, using organelle-resolution proteomics, we identify member a2 solute carrier 37 family (Slc37a2) SL sugar transporter. We demonstrate in mice...
The parathyroid hormone 1 receptor (PTHR) is central to the process of bone formation and remodeling. PTHR signaling requires internalization into endosomes, which then terminated by recycling or degradation. Here we show that sorting nexin 27 (SNX27) functions as an adaptor couples retromer trafficking complex. SNX27 binds directly C-terminal PDZ-binding motif PTHR, wiring it for endosomal sorting. structure bound reveals a high-affinity interface involving conserved electrostatic...
Obesity is a well-recognised risk factor for osteoarthritis (OA). Our aim to characterise body mass index (BMI)-associated pathological changes in the osteochondral unit and determine if obesity major causal antecedent of early joint replacement patients with OA.We analysed correlation between BMI age at which undergo total knee (TKR) 41 023 from Australian Orthopaedic Association National Joint Replacement Registry. We then investigated effect on tibia plateau representative subset...
Abstract Tendinopathy is one of the most common musculoskeletal diseases, and mechanical overload considered its primary cause. However, underlying mechanism through which induces tendinopathy has not been determined. In this study, we identified for first time that tendon cells can release extracellular mitochondria (ExtraMito) particles, a subtype medium particles (mEPs), into environment process regulated by loading. RNA sequencing systematically revealed oxygen-related reactions,...
The NFκB pathway plays a critical role in the regulation of osteoclast activity, and activation is dependent on IκB kinase (IKK), which phosphorylates IκB, targeting it for proteasomal degradation. Pharmacological inhibitors IKK exhibit anti-inflammatory properties prevent bone erosions models inflammatory arthritis. However, effects these agents osteoblast function ovariectomy-induced loss remain unknown. Here we examined celastrol, BMS-345541, parthenolide cell vitro vivo. All three...
Guided bone regeneration is one of the most common surgical treatment modalities performed when an additional alveolar required to stabilize dental implants in partially and fully edentulous patients. The addition a barrier membrane prevents non-osteogenic tissue invasion into cavity, which key success guided regeneration. Barrier membranes can be broadly classified as non-resorbable or resorbable. In contrast membranes, resorbable do not require second procedure for removal. Commercially...
Rotator Cuff (RC) tendon tearing is a common clinical problem and there high incidence of revision surgery due to re-tearing. In an effort improve patient outcome reduce surgical revision, scaffolds have been widely used for augmentation RC repairs. However, little known about how support stem cell growth or facilitate regeneration. The purpose this study evaluate the structural biological properties bioactive collagen scaffold (BCS) with potential promote repair. Additionally, we conducted...
Botulinum toxin (Botox) injection is in widespread clinical use for the treatment of muscle spasms and tendinopathy but mechanism action poorly understood. We hypothesised that reduction patellar-tendon mechanical-loading following intra-muscular Botox results tendon atrophy at least part mediated by induction senescence tendon-derived stem cells (TDSCs). Controlled laboratory study METHODS: A total 36 mice were randomly divided into 2 groups (18 Botox-injected 18 vehicle-only control). Mice...
Abstract Background Epineurium acts as a barrier to protect nerves from injury and maintains its structural functional integrity. A device was developed mimic the native structure of epineurium. The aim this study evaluate biological characteristics clinical performance in reconstruction upper extremity peripheral nerves. Methods Scanning electron microscopy, transmission enhanced microcomputed tomography were used examine ultrastructural device. prospective case series with 2-year follow-up...