25 research outputs found
Pharmacologic Inhibition of the TGF-β Type I Receptor Kinase Has Anabolic and Anti-Catabolic Effects on Bone
During development, growth factors and hormones cooperate to establish the unique sizes, shapes and material properties of individual bones. Among these, TGF-β has been shown to developmentally regulate bone mass and bone matrix properties. However, the mechanisms that control postnatal skeletal integrity in a dynamic biological and mechanical environment are distinct from those that regulate bone development. In addition, despite advances in understanding the roles of TGF-β signaling in osteoblasts and osteoclasts, the net effects of altered postnatal TGF-β signaling on bone remain unclear. To examine the role of TGF-β in the maintenance of the postnatal skeleton, we evaluated the effects of pharmacological inhibition of the TGF-β type I receptor (TβRI) kinase on bone mass, architecture and material properties. Inhibition of TβRI function increased bone mass and multiple aspects of bone quality, including trabecular bone architecture and macro-mechanical behavior of vertebral bone. TβRI inhibitors achieved these effects by increasing osteoblast differentiation and bone formation, while reducing osteoclast differentiation and bone resorption. Furthermore, they induced the expression of Runx2 and EphB4, which promote osteoblast differentiation, and ephrinB2, which antagonizes osteoclast differentiation. Through these anabolic and anti-catabolic effects, TβRI inhibitors coordinate changes in multiple bone parameters, including bone mass, architecture, matrix mineral concentration and material properties, that collectively increase bone fracture resistance. Therefore, TβRI inhibitors may be effective in treating conditions of skeletal fragility
The molecular logic of endocannabinoid signalling
The endocannabinoids are a family of lipid messengers that engage the cell surface receptors that are targeted by Δ9-tetrahydrocannabinol, the active principle in marijuana (Cannabis). They are made on demand through cleavage of membrane precursors and are involved in various short-range signalling processes. In the brain, they combine with CB1 cannabinoid receptors on axon terminals to regulate ion channel activity and neurotransmitter release. Their ability to modulate synaptic efficacy has a wide range of functional consequences and provides unique therapeutic possibilities. © 2003, Nature Publishing Group. All rights reserved
Childhood victimization and subsequent risk for promiscuity, prostitution, and teenage pregnancy: a prospective study.
A MBP-FAAH fusion protein as a tool to produce human and rat fatty acid amide hydrolase: expression and pharmacological comparison
Clinical pharmacist’s contribution to medication reconciliation on admission to hospital in Ireland
Performance in a GO/NOGO perceptual task reflects a balance between impulsive and instrumental components of behaviour
Effect of Au Addition on the Catalytic Performance of CuO/CeO2 Catalysts for CO2 Hydrogenation to Methanol
A comparative study of marshall score versus apache-II score in assessing severity of acute pancreatitis
Kratos universidad EAFIT: A new platform to live learning experiences
[No abstract available