Effect of ternary phosphate-based glass compositions on osteoblast and osteoblast-like prolferation, differentiation and death in vitro

There is currently a need to expand the range of graft materials available to orthopaedic surgeons. This study investigated the effect of ternary phosphate based glass (PBG) compositions on the behaviour of osteoblast and osteoblast-like cells. PBGs of the formula in mol% P2O5 (50)-CaO (50-X)-Na2O (X), where X was either 2, 4, 6, 8 or 10 were produced and their influence on the proliferation, differentiation and death in vitro of adult human bone marrow stromal cells (hBMSCs) and human fetal osteoblast 1.19 (HFOB 1.19) cells were assessed. Tissue culture plastic (TCP) and hydroxyapatite (HA) were used as controls. Exposure to PBGs in culture inhibited cell adhesion, proliferation and increased cell death in both cell types studied. There was no significant difference in %cell death between the PBGs which was significantly greater than the controls. However, compared to other PBGs, a greater number of cells was found on the 48 mol% CaO which may have been due to either increased adherence, proliferation or both. This composition was capable of supporting osteogenic proliferation and early differentiation and supports the notion that chemical modification of the glass could to lead to a more biologically compatible substrate with the potential to support osteogenic grafting. Realisation of this potential should lead to the development of novel grafting strategies for the treatment of problematic bone defects.

Review: formation and properties of amyloid-like fibrils derived from alpha-synuclein and related proteins.

Synucleins are small proteins that are highly expressed in brain tissue and are localised at presynaptic terminals in neurons. alpha-Synuclein has been identified as a component of intracellular fibrillar protein deposits in several neurodegenerative diseases, and two mutant forms of alpha-synuclein have been associated with autosomal-dominant Parkinson's Disease. A fragment of alpha-synuclein has also been identified as the non-Abeta component of Alzheimer's Disease amyloid. In this review we describe some structural properties of alpha-synuclein and the two mutant forms, as well as alpha-synuclein fragments, with particular emphasis on their ability to form beta-sheet on ageing and aggregate to form amyloid-like fibrils. Differences in the rates of aggregation and morphologies of the fibrils formed by alpha-synuclein and the two mutant proteins are highlighted. Interactions between alpha-synuclein and other proteins, especially those that are components of amyloid or Lewy bodies, are considered. The toxicity of alpha-synuclein and related peptides towards neurons is also discussing in relation to the aetiology of neurodegenerative diseases.