A5082454972- Bone Metabolism and Diseases
- Bone health and treatments
- Cannabis and Cannabinoid Research
- NF-κB Signaling Pathways
- Bone health and osteoporosis research
- Forensic Toxicology and Drug Analysis
- Neuroscience and Neuropharmacology Research
- Biochemical effects in animals
- Estrogen and related hormone effects
- Cytokine Signaling Pathways and Interactions
- Inflammatory mediators and NSAID effects
- Pharmacological Effects and Toxicity Studies
- Metabolism, Diabetes, and Cancer
- Cancer-related Molecular Pathways
- Bone and Joint Diseases
- Pharmacological Receptor Mechanisms and Effects
- Diet and metabolism studies
- Pancreatic function and diabetes
- Growth Hormone and Insulin-like Growth Factors
- Medical and Biological Sciences
- Spectroscopy Techniques in Biomedical and Chemical Research
- Cancer therapeutics and mechanisms
- Osteoarthritis Treatment and Mechanisms
- TGF-β signaling in diseases
- Cancer Treatment and Pharmacology
University of Sheffield
2014-2025
Edinburgh Cancer Research
2010-2021
Institute of Genetics and Cancer
2009-2021
Western General Hospital
2008-2020
University of Edinburgh
2006-2017
Western Hospital
2008
University of Aberdeen
2004-2007
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...
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...
The endocannabinoid system plays a key role in regulating variety of physiological processes such as appetite control and energy balance, pain perception, immune responses. Recent studies have implicated the regulation bone cell activity remodeling. These showed that endogenous cannabinoid ligands, receptors, enzymes responsible for ligand synthesis breakdown all play important roles mass disease. findings suggest pathway could be value therapeutic target prevention treatment diseases. Here,...
The endocannabinoid system plays a role in regulating bone mass and cell activity inactivation of the type 1 (Cnr1) or 2 (Cnr2) cannabinoid receptors influences peak age-related loss. As Cnr1 Cnr2 have limited homology are activated by different ligands, we evaluated effects combined deficiency (Cnr1/2-/- ) on development from birth to old age studied ovariectomy induced loss female mice. Cnr1/2-/- mice had accelerated accrual at when compared with wild littermates, 3 months age, they higher...
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...
Hydrogen sulphide (H(2)S) and prostaglandins are both involved in inflammation, cancer bone turnover, non-steroidal anti-inflammatory drugs (NSAIDs) H(2)S donors exhibit anti-tumour properties. H(2)S-releasing diclofenac (S-DCF) derivatives a novel class of NSAIDs combining the properties donor with those conventional NSAID.We studied effects S-DCF ACS15 ACS32 on osteoclast osteoblast differentiation activity vitro, human mouse breast cells support for formation signalling osteolysis ex...
The cannabinoid type 2 receptor (CB2) has previously been implicated as a regulator of tumor growth, bone remodeling, and pain. However, very little is known about the role skeletal CB2 in regulation osteoblasts osteoclasts changes associated with breast cancer. Here we found that CB2-selective agonists HU308 JWH133 reduced viability variety parental bone-tropic human mouse cancer cells at high micromolar concentrations. Under conditions which these ligands are used nanomolar range, enhanced...
Abstract NFκB plays an important role in inflammation and bone remodelling. Tumour necrosis factor receptor associated 2 (TRAF2), a key component of signalling, has been identified as oncogene, but its the regulation breast cancer osteolytic metastasis remains unknown. Here, we report that stable overexpression TRAF2 parental osteotropic sub-clones human MDA-MB-231 (MDA-231) cells increased cell growth motility vitro , whereas knockdown was inhibitory. In vivo MDA-231-P enhanced tumour after...
Abstract To test the hypothesis that genetic and pharmacological modulation of classical cannabinoid type 1 (CB ) 2 receptors attenuate cancer-induced bone pain, we searched Medline, Web Science Scopus for relevant skeletal non-skeletal cancer studies from inception to July 28, 2022. We identified 29 animal 35 human studies. In mice, a meta-analysis pooled showed treatment osteolysis-bearing males with endocannabinoids AEA 2-AG (mean difference [MD] − 24.83, 95% confidence interval [ CI]...