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The University of Southampton
Medicine

Bone and Joint Diseases

The aims of the bone and joint theme are firstly, to increase our understanding of the mechanisms which connect early development to later risk of osteoporosis and other musculoskeletal disorders, and secondly to develop intervention studies aimed at reducing the risk of these diseases of older age through interventions targeted at critical periods of development in early life.

Image of child
pQCT examination of a child

In this theme we address the developmental origins of osteoporotic fracture from molecule to population (see image above), using laboratory and clinical observational and interventional studies.

Basic science

Professor Richard Oreffo, Professor Cyrus CooperDr Christopher Edwards, Professor Nicholas Clarke, Mr Douglas Dunlop and Dr Stuart Lanham

The Bone and Joint Research Group led by Professor Richard Oreffo, has vast expertise in bone and stem cell biology and fracture repair. This expertise is being used to determine how, alterations in early development, affects bone and stem cells and how this may increase the likelihood of osteoporosis in later life. Located in the Institute of Developmental Sciences, the group is perfectly placed to link with other areas of developmental research across Life Sciences. 

The group has shown that:

  1. A maternal diet low in protein induces osteoporosis in old female offspring.
  2. A maternal high fat diet alters the bone structure of offspring.
  3. Removal of different hormones has different effects on developing bone structure. These experimental results are similar to those seen through epidemiological studies and the mechanism involved in these alterations are currently being examined at the molecular level.

MRC Lifecourse Epidemiology Unit:  Clinical and translational research

Professor Cyrus Cooper, Professor Elaine Dennison, Dr Nicholas Harvey, Professor Nigel Arden, Dr Kassim Javaid

The MRC Lifecourse Epidemiology Unit is an internationally-renowned institution, focusing on the clinical and translational approach to these research aims. Previous work has demonstrated:

  1. Poor early growth predicts an increased risk of osteoporotic fracture in older age; this may be mediated through altered bone geometry and biomechanical properties.
  2. Maternal vitamin D insufficiency during pregnancy is associated with reduced bone mass in the offspring.
  3. Confirmation that maternal lifestyle, body build and physical activity predict bone size and shape in the offspring.

Over the next five years, the international cohorts curated by the unit (including Hertfordshire Cohort Study, Helsinki Growth Study, and Southampton Women's Survey) will be used to further characterise the relationships between early growth and later bone size, geometry, density and fracture risk; the environmental factors in early life which influence long term skeletal development will also be elucidated. Outcomes measures available include DXA, pQCT, MRI and objectively measured physical activity.  Additionally, these cohort resources will contribute, as part of large international consortia, to the understanding of the genetic aspects of fracture risk through genome-wide screening. Informed by the epidemiological findings, a centrepiece of the programme will be the first randomised controlled trial to investigate whether supplementation of vitamin D during pregnancy serves to optimise skeletal development in the offspring (MAVIDOS).  The MAVIDOS study and observational cohorts provide valuable sources of tissue (umbilical cord, placenta, blood) and carefully characterised phenotypes in which to explore the epigenetic regulation of processes such as placental calcium transport, which might be key to these observations. In adult life, the efficacy of novel screening strategies for osteoporosis risk will be tested (MRC SCOOP study) and through collaboration with NIHR Biomedical Research Unit in Musculoskeletal Science, University of Oxford, a research programme addressing the lifecourse epidemiology of osteoarthritis and arthroplasty is under way. The eventual hope is to inform the development of novel public health strategies to improve skeletal health throughout the lifecourse, and reduce osteoporotic fractures and osteoarthritis in future generations. 


Bone and cartilage tissue engineering

Dr Janos Kanczler, Dr Nicholas Evans, Dr Ben MacArthur, Dr Bram Sengers, Dr Rahul Tare, Mr Douglas Dunlop, Professor Richard Oreffo

Bone fractures repair spontaneously with minimal treatment or scarring. However, in some clinical settings, large sections of bone samples are required to treat skeletal defects. Additionally, with an increasing aging population hip fracture repair procedures are set to increase placing an even greater demand for bone replacement products. Our research is centred on developing bone tissue engineering strategies using the elements of scaffold / biomaterial design (Fig. 1a-c) to provide biocompatible materials for orthopaedic replacement therapies.

In a number of collaborations we have created scaffold constructs to promote cell adhesion, growth (Fig. 1c) differentiation and cell-matrix interaction to promote osteogenesis and angiogenesis for bone repair strategies.

Growth factors such as Bone Morphogenic Protein-2 (BMP-2) and Vascular Endothelial Growth Factor (VEGF) have been engineered to be released in an active form to stimulate cell growth and differentiation to repair bone in a critical sized defect model (Fig. 2).

Key for bone tissue engineering is developing a blood supply to the newly implanted construct. We are developing ways to enhance the angiogenic response to coincide with the bone repair sequences in the critical size defects (Fig. 3).

Osteoarthritis is a degenerative joint disorder where the cartilage and bone have eroded away. We are currently applying tissue enginerering strategies to develop cartilage engineered constructs for application in repair and replacement therapies for this debilatating skeletal disease (Fig. 4).

Awards and Prizes

2008
Awarded to Andrew Jones
Gauvain Society Annual Conference 2008 prize for oral presentation.

2009
Awarded to Alexander Aarvold
University of Southampton Translation Research Conference November 2009 Poster Presentation, 2nd Prize
NHS Education South Central (NESC) Travelling Fellowship visit to Rizzoli Orthopaedic Institute, Bologna, Italy October 2009

Awarded to Andrew Jones
Selected for the Best of the Best section, BOA 2009. Best of the Best abstract.  

2010
Awarded to Alexander Aarvold
Gauvain 2010, 3rd Prize
Winner, Grand Prix: “The Engineer” Technology & Innovation Awards 2010; “Development of a Novel Orthopaedic Stem Cell Concentrator”
Winner, Medical & Healthcare Category: “The Engineer” Technology & Innovation Awards 2010; “Development of a Novel Orthopaedic Stem Cell Concentrator”
No.1 invention, “Top Ten of 2010” Medical Device Developments, Orthopaedic Stem Cell Concentrator

Awarded to Andrew Jones
Medical/Healthcare section winner. The Engineer Awards 2010
Grand Prix award for overall winner. The Engineer Awards 2010
Awarded top medical device of 2010. Orthopaedic Stem cell concentrator developed in conjunction with Smith & Nephew. Top Ten of 1010.

2011
Awarded to Alexander Aarvold
Gauvain 2011, 2nd Prize
Pfizer Award, Best Clinical Translation Poster, UK National Stem Cells Network , Annual Conference York, March 2011

Awarded to Andrew Jones
Postgraduate Research Conference, Southampton 2011. 1st Prize

Awarded to Edward Tayton
Conference attended award (University of Southampton) November 2011
BORS Cambridge 2011, 1st Prize

2012
Awarded to Edward Tayton
Gauvain 2012, 1st Prize
Translational Clinical Research Conference 2012 (University of Southampton 1st Prize

2013

At the Postgraduate Research Showcase held on Thursday 2nd May at Highfield Marco Peca from the Bone and Joint group was awarded Highly Commended for his poster display.  Please click here for more information.

Dr David Gothard wins Biomedical Imaging Unit Micrograph 2013.  Please click here for more information.

2014

We are pleased to announce that Medicine has been awarded a Diamond Jubilee International Visiting Fellowship. Professor Richard Oreffo will be hosting Professor Kenneth Lee (Chinese University of Hong Kong).

And now the good news…

Honours

Southampton audiology lecturer receives prestigious international award
Dr Daniel Rowan
has been awarded the prestigious Denzil Brooks Trophy from the British Society of Audiology (BSA). Find out more here

Award for innovative research on cartilage engineering
Postgraduate research student Siwei Li has won the New Investigator award for his work on cartilage engineering at the 4th Joint Meeting of the Bone Research Society and the British Orthopaedic Research Society in Oxford. Find out more here

ISVR student Matthew Reynolds has won two Acoustics award
Matthew Reynolds
, was recently awarded two acoustics awards for his research in acoustic metamaterials. Find out more

James O Smith, Edward R Tayton, Ferdous Khan, Alexander Aarvold, Richard B Cook, Allen Goodship, Mark Bradley, Richard OC Oreffo. Large animal in vivo evaluation of binary blend polymer scaffold for skeletal tissue. Gauvain Society Annual Scientific Meeting, Southampton. Second prize for podium presentation 2014.

Laponite - synthetic clay gel (a); PLA (b); PLA + HBMSC (c)
Fig 1
Alginate/PLA (A); Alginate-VEGF/PLA-BMP-2 + HBMSC (B)
Fig 2
3D image of perfused contrast vascular dye (red) depicting the blood vessels in a critical sized bone defect
Fig 3
Broken bones
Fig 4
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