Bone Abstracts

In bone marrow, bone marrow stromal cells (BMSCs) have the capacity to differentiate into osteoblasts and adipocytes. Onset of osteoporosis with age stems in part from the enhanced bone marrow adipogenesis that represses osteogenesis. In this study, we demonstrate that disruption of nuclear factor I-C (NFI-C) impairs osteoblast differentiation and bone formation, and increases bone marrow adipocytes. Interestingly, NFI-C controls postnatal bone formation but does not influence...

C-C chemokine receptor 5 (CCR5) is a co-receptor of macrophage-tropic viruses including HIV. Epidemiological and pathological findings have reported that functional changes in CCR5 correlate with HIV transmission bone destruction disease. However, the roles of CCR5 in bone pathophysiology have not been well documented.Ccr5-deficient osteoclasts showed decreased bone resorption activity accompanied with disorganized cellular architecture and impa...

Introduction: Activated protein C (APC) plays an important role in the cutaneous healing of chronic wounds arising from orthopaedic surgery and has cytoprotective and anti-inflammatory properties which may also assist bone repair. The aim of this study was to examine whether APC could directly influence osteoblasts and increase bone formation in a rodent model.Methods: Proliferation of MG-63 osteoblast-like cells was quantified by MTT assay and direct co...

RANKL induced osteoclastogenesis is mediated by several transcription factors such as NF-κB, AP-1 and Nfatc1. We have found that also cysteine proteinases are involved in the signaling pathway downstream RANK. Thus, cystatin C, Z-RLVG-CHN2 (the sequence of which is based upon one of the enzyme inhibitory domains in cystatin C) and the fungal molecule E-64 – inhibit RANKL induced mouse and human osteoclast formation in vitro (Strålberg et ...

Tyrosine kinase c-Src plays an important role in actin ring formation and bone resorption activity in osteoclasts. Therefore, c-Src has been targeted for the treatment of osteolytic disorders. In the present study, we investigated anti-resorptive effect of dibenzazepine (DBZ), one of the γ-secretase inhibitors (GSIs), on osteoclast-mediated excessive bone resorption. DBZ did not affect osteoclast differentiation, but disturbed actin ring formation and inhibited osteoclast...

Distal-less homeobox 5 (Dlx5) is a transcription factor that enhances osteogenic differentiation of mesenchymal stem cells via upregulating the expression of Runx2 and other osteoblast phenotypic genes. We have previously demonstrated that Dlx5 also downregulates adipogenic differentiation of mesenchymal stem cells and that insulin decreases expression levels of Dlx5 via increasing expression levels of miR-124, a microRNA targeting 3′UTR of Dlx5. However, the mechanism o...

High Bone Mass (HBM) osteogenesis imperfecta (OI) is caused by dominant mutations in the C-propeptide cleavage site of COL1A1 or COL1A2, characterized by bone hypermineralization. To elucidate the role of C-propeptide processing in bone mineralization and development, we generated heterozygous HBM mice with both residues (Ala-Asp) of the COL1A1 cleavage site substituted (Thr-Asn) to prevent processing by BMP1. Two, 6- and 12-month WT and HBM bones were examin...

Kit ligand/c-Kit receptor tyrosine kinase complex has been implicated as a target for bone remodeling process. Loss of function mutation in c-Kit causes low bone mass in KitW/W-v (W/Wv) mice. However, these mice are sterile and it is unclear whether the observed skeletal phenotype is secondary to sex hormone deficiency. To address this question, the skeletal phenotype of KitW...

Inflammatory processes play a role in osteoclastogenesis. C-reactive protein (CRP), an acute phase reactant that reflects different degree of inflammation. More recently, accumulating evidence suggest that CRP is not only an inflammatory marker but also direct cause of diseases. Therefore, we examined the direct effects of CRP on osteoclast formation using RAW 264.7 cells. CRP significantly inhibited RANKL-induced TRAP-positive multinucleated cell formation in RAW 264.7 cell c...

Biographical DetailsAmaka C Offiah is Senior Lecturer and Consultant Paediatric Radiologist at the University of Sheffield and Sheffield Children’s Hospital. She has a specialist interest in the musculoskeletal system. She has co-authored two books, seven book chapters, published 67 peer-reviewed articles and given over 100 invited national and international lectures. She is Convenor...