Bone Abstracts

Identifying novel approaches for enhancing osteoblast (OB) differentiation of human skeletal (mesenchymal) stem cells (hMSC) can lead to development of novel anabolic agents required for efficient bone formation. Transforming growth factor-βs (TGF-β1, 2, 3) are one of the most abundant growth factors in bone and play a key role in regulating bone remodeling. Canonical TGF-β signaling inhibits, whereas components of the non-canonical TGF-β signaling (e.g. Ak...

Background: Hypoxia induces mesenchymal stem cells (MSCs) proliferation but results in a population with impaired osteogenic differentiation potential. Bone healing of tibial lengthening is enhanced by hyperbaric oxygen therapy. However, little is known about the effects of HBO on the Wnt signaling pathway in MSCs.Materials and methods: MSCs were cultured in complete medium and the osteogenic groups were cultured in osteogenic induction medium. Control c...

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Identifying novel molecules that enhance human skeletal (mesenchymal) stem cells (hMSC) differentiation into osteoblastic bone forming cells (OB), may lead to development of new bone anabolic drugs. We have identified Kix, a small molecule kinase inhibitor that enhanced ex vivo OB differentiation and reduced apoptosis of hMSC. We found that Kix targeted undifferentiated hMSC populations and not their differentiated progeny. In addition, Kix increased in vivo ...

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The molecular mechanisms underlying telomere shortening and telomerase deficiency contributing to defective age-related bone formation are poorly studied. We have previously demonstrated the role of telomerase re-activation in enhancing osteoblast differentiation of BMSCs in vitro and in vivo. Here, we investigated further the signaling pathways underlying the regulatory function of telomerase in osteogenesis. Comparative microarray analysis of telomerase-ove...

Introduction: Children with chronic kidney disease (CKD) who suffer from growth retardation have usually normal circulating GH but low IGF1, suggesting GH resistance. We have previously shown in growth retarded CKD rats an increase in suppressor of cytokine signaling 2 (SOCS2) levels, a key negative regulator of GH signaling. SOCS2 spontaneously mutated (HG) mice show an exaggerated body growth and increased bone mass. We investigated growth and GH receptor (GHR) signaling in ...

Introduction: Insulin sensitising agents are reported to have a diverse range of effects on bone with metformin exerting positive effects and thiazolidinenediones (TZDs) exerting negative effects. 5’AMP-activated protein kinase (AMPK) plays a critical role in cellular energy homeostasis. It is widely expressed in the body and can be activated by metformin.Objective:: We investigated the role of AMPK pathway in mediating the effects of metformin on t...

Background and objective: High-resolution magnetic resonance imaging (hrMRI) can assess trabecular bone microarchitecture but the number of image slices required for reliable assessment is unclear.Methods: MRI was performed just below the growth plate of the proximal tibia from 20 healthy controls (all female; median age 21 years (range 18–35) and 10 cases (three mals: seven females; median age 19.5 years (range 16–48) with known bone abnormali...

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