In parallel with clinical and epidemiological studies this work addresses three themes: developmental origins of bone health, skeletal differentiation and function; chondroepiphyseal growth and development, including basic mechanisms of osteoarthritis (OA); and musculoskeletal regeneration and mesenchymal stem cells.
Research into the developmental origins of bone health is funded through a 4 year programme (Richard Oreffo, Nick Clarke, Trudy Roach, Cyrus Cooper). The work has established (using rat/ovine models) that a low protein diet influences the osteogenic environment of offspring. Ex vivo models of skeletal differentiation from multipotent adult and fetal stem cells have been developed to inform this process. We were the first to report on epigenetic influences on the risk of osteoarthritis. The group has developed unique tools and protocols to isolate human mesenchymal populations allowing the use of a variety of approaches to modulate differentiation along stromal lineages for tissue regeneration of bone and cartilage. This work has permitted development of human fetal-derived mesenchymal stem cells as well as the use of innovative materials and mathematical modelling strategies to drive tissue regeneration. This research is an important contributor to the University's Life Sciences Interface, with the School of Engineering Sciences and Institute of Sound and Vibration Research.
Current studies include:
- Selection of bone-marrow derived stem cells
- Modulation of osteogenic and chondrogenic differentiation of human bone marrow-derived osteoprogenitor cells.
- Bone and cartilage tissue engineering
- Effects of epigenetic modifiers on differentiation pathways
- Basic cartilage biology
- Epigenetic changes in osteoarthritis
- Effects of inflammatory cytokines on gene expression and DNA methylation
- Developmental origins (fetal programming) of skeletal growth
Understanding these processes has tremendous therapeutic potential for many skeletal disorders, ranging from faulty hip development in children to osteoarthritis and osteoporosis in the elderly. Skeletal tissue engineering also holds the tremendous promise for replacing lost or damaged bone or cartilage.