OSTEOARTHRITIC SUBCHONDRAL BONE MARROW HISTOLOGY. LESSONS FROM CHANGES IN ALKAPTONURIA

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Fragmenting densely mineralised acellular protrusions from articular calcified cartilage: a role in osteoarthritis?

Fragmenting densely mineralised acellular protrusions from articular calcified cartilage: a role in osteoarthritis? A. Boyde a, G.R. Davis a, D. Mills a, T. Zikmund a, V.L. Adams b, L.R. Ranganath b, N. Jeffery b, J.A. Gallagher b a Dental Physical Sciences, Oral Growth and Development, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK b Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK Objectives High density mineralised protrusions (HDMP) from the tidemark mineralising front into hyaline articular cartilage (HAC) were first discovered in Thoroughbred racehorse fetlock joints and later in Icelandic horse hock joints. If these fragment, they could make a significant contribution to joint destruction in osteoarthritis. We looked for them in human material. Methods Whole femoral heads removed at operation for joint replacement or from dissection room cadavers were studied by MRI DESS at 0.23mm resolution and 26 micron resolution high contrast x-ray microtomography (XMT), then sectioned and embedded in PMMA, and block faces polished and the blocks re-imaged with 6 micron resolution XMT. Tissue mineralisation density was imaged qualitatively by backscattered electron SEM (BSE SEM) at 20kV using uncoated samples at 50Pa chamber pressure to achieve charge neutralisation. HAC histology was studied by BSE SEM after staining block faces with ammonium triiodide solution. Block surfaces were sequentially repolished and restained. Results Figure: 3D rendering of 6 micron voxel resolution XMT data set showing HDMP complex projecting above subchondral bone plate. Human femoral head removed at arthroplasty. We found examples of HDMP in HAC in human hips. Their 3D shapes are complex and may show cutting blade forms. Their mineral content (a) exceeds that of articular calcified cartilage (ACC), otherwise the densest tissue in the joint and (b) is not uniform. The mineral phase morphology frequently shows the agglomeration of many fine particles into larger concretions. Cracks within them are frequent. Dense fragments may be found within damaged HAC. Conclusions HDMP arise via the extrusion of an uncharacterised matrix into clefts in HAC. Little evidence of their existence remains after tissue has been decalcified with usual histological protocols. Their formation may be an extension of a normal but poorly recognised crack self-healing mechanism found in bone and ACC. They are surrounded by HAC, are dense and brittle and show innumerable fault lines within them. We provide evidence that they break in vivo by being able to find matching fragments in HAC. We conclude that these hard and sharp particles contribute to the shredding destruction of HAC. The osteoarthritis research community should be aware of their existence so that the frequency and possible clinical significance can be assessed in the future. Larger HDMP can be detected with the best MRI imaging

Rarer insights from rarer microscopies in the study of the rare bone disease AKU.

Rarer insights from rarer microscopies in the study of the rare bone disease AKU. Thurs Oct 16th 2014 Rare bone diseases meeting Stockholm A. Boyde, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK L.R. Ranganath & J.A. Gallagher, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK [email protected] We have conducted 3D microscopic studies of surgical retrieval tissue from alkaptonuria (AKU) patients, who develop severe forms of osteoarthritis (OA). The methods used include serial sectioning of decalcified material, but more importantly, methods which avoid any risk of decacification or deformation by physical sectioning. We group these methods together under the heading block or block-face microscopy. These include BSE SEM, CSLM and dynamic aperture microscopy and x-ray microtomography. We discovered marked peculiarities in AKUbone and later looked to see if some of these were replicated in non-AKU OA - and they were. These include trabecular excrescences and hyperdense mineralised protrusions (HDMPs) from the tidemark mineralising front in articular calcified cartilage. Thus the rare disease AKU gives insights into disease mechanisms and consequences in a very common disease, OA. At QMUL, we are proud of the fact that the main medical school building at the old London Hospital Medical College of the new Barts' and The London School of Medicine and Dentistry was renamed after the man who put the genetic disease AKU on the map, Archibald Garrod

Growth and dislocation studies of β-HMX

Background: The defect structure of organic materials is important as it plays a major role in their crystal growth properties. It also can play a subcritical role in “hot-spot” detonation processes of energetics and one such energetic is cyclotetramethylene-tetranitramine, in the commonly used beta form (β-HMX). Results: The as-grown crystals grown by evaporation from acetone show prismatic, tabular and columnar habits, all with {011}, {110}, (010) and (101) faces. Etching on (010) surfaces revealed three different types of etch pits, two of which could be identified with either pure screw or pure edge dislocations, the third is shown to be an artifact of the twinning process that this material undergoes. Examination of the {011} and {110} surfaces show only one type of etch pit on each surface; however their natural asymmetry precludes the easy identification of their Burgers vector or dislocation type. Etching of cleaved {011} surfaces demonstrates that the etch pits can be associated with line dislocations. All dislocations appear randomly on the crystal surfaces and do not form alignments characteristic of mechanical deformation by dislocation slip. Conclusions: Crystals of β-HMX grown from acetone show good morphological agreement with that predicted by modelling, with three distinct crystal habits observed depending upon the supersaturation of the growth solution. Prismatic habit was favoured at low supersaturation, while tabular and columnar crystals were predominant at higher super saturations. The twin plane in β-HMX was identified as a (101) reflection plane. The low plasticity of β-HMX is shown by the lack of etch pit alignments corresponding to mechanically induced dislocation arrays. On untwinned {010} faces, two types of dislocations exist, pure edge dislocations with b = [010] and pure screw dislocations with b = [010]. On twinned (010) faces, a third dislocation type exists and it is proposed that these pits are associated with pure screw dislocations with b = [010]

An upper limit on the contribution of accreting white dwarfs to the type Ia supernova rate

There is wide agreement that Type Ia supernovae (used as standard candles for cosmology) are associated with the thermonuclear explosions of white dwarf stars. The nuclear runaway that leads to the explosion could start in a white dwarf gradually accumulating matter from a companion star until it reaches the Chandrasekhar limit, or could be triggered by the merger of two white dwarfs in a compact binary system. The X-ray signatures of these two possible paths are very different. Whereas no strong electromagnetic emission is expected in the merger scenario until shortly before the supernova, the white dwarf accreting material from the normal star becomes a source of copious X-rays for ~1e7 yr before the explosion. This offers a means of determining which path dominates. Here we report that the observed X-ray flux from six nearby elliptical galaxies and galaxy bulges is a factor of ~30-50 less than predicted in the accretion scenario, based upon an estimate of the supernova rate from their K-band luminosities. We conclude that no more than ~5 per cent of Type Ia supernovae in early type galaxies can be produced by white dwarfs in accreting binary systems, unless their progenitors are much younger than the bulk of the stellar population in these galaxies, or explosions of sub-Chandrasekhar white dwarfs make a significant contribution to the supernova rate.Comment: 10 pages, 1 tabl

Detection of Massive Forming Galaxies at Redshifts Greater than One

The complex problem of when and how galaxies formed has not until recently been susceptible of direct attack. It has been known for some time that the excessive number of blue galaxies counted at faint magnitudes implies that a considerable fraction of the massive star formation in the universe occurred at z < 3, but, surprisingly, spectroscopic studies of galaxies down to a B magnitude of 24 found little sign of the expected high-z progenitors of current massive galaxies, but rather, in large part, small blue galaxies at modest redshifts z \sim 0.3. This unexpected population has diverted attention from the possibility that early massive star-forming galaxies might also be found in the faint blue excess. From KECK spectroscopic observations deep enough to encompass a large population of z > 1 field galaxies, we can now show directly that in fact these forming galaxies are present in substantial numbers at B \sim 24, and that the era from redshifts 1 to 2 was clearly a major period of galaxy formation. These z > 1 galaxies have very unusual morphologies as seen in deep HST WFPC2 images.Comment: 10 pages LaTeX + 5 PostScript figures in uuencoded gzipped tar file; aasms4.sty, flushrt.sty, overcite.sty (the two aastex4.0 and overcite.sty macros are available from xxx.lanl.gov) Also available (along with style files) via anonymous ftp to ftp://hubble.ifa.hawaii.edu/pub/preprints . E-print version of paper adds citation cross-references to other archived e-prints, where available. To appear in Nature October 19, 199