Kwan, Alvin - Cardiff University - School of Biosciences

研究领域

Bones grow and repair mainly via a complex developmental process known as endochondral ossification in which ossification occurs within a specialised hyaline cartilaginous matrix. In the long bones, this hyaline cartilage is known as the epiphyseal growth plate. Within the growth plate, chondrocytes undergo a stringently controlled developmental sequence leading to terminal chondrocyte differentiation (cell hypertrophy) prior to the transition from cartilage to bone. Chondrocyte differentiation is therefore an important prerequisite of normal bone formation. Current research activities in my laboratory have focussed mainly on two potential regulators of cell differentiation in the growth plate. Type X collagen – an extracellular matrix molecule which forms a mat-like network around differentiating chondrocytes in the hypertrophic cartilage matrix. Its expression is reinitiated in mature articular cartilage in osteoarthritis and is thought to be the consequence of tissue repair and osteophyte formation. We have identified several receptors for type X collagen on the surface of hypertrophic chondrocytes, these include the integrin a 2 b 1 and the collagen receptors DDR1 and DDR2. We are particularly interested in studying the mechanisms of interactions, the biological effects and signalling events following receptor-type X binding. Small Acidic Protein (SAP) – a 172 amino acid bHLH-like nuclear protein which is downregulated during chondrocyte hypertrophy and by cyclopamine, an inhibitor of the Hedgehog signalling pathway. We hypothesise that SAP is a novel transcription factor that attenuates chondrocyte differentiation in the epiphyseal growth plate. We are interested in investigating the roles of SAP in endochondral ossification and the characterization of the Hedgehog-responsive element(s) of the SAP gene. We also study the regulation of SAP expression in other disease models such as atherosclerosis.

近期论文

查看导师新发文章（温馨提示：请注意重名现象，建议点开原文通过作者单位确认）

Lee, P.et al. 2016. Should we treat soft tissue injuries with Actovegin. EC Orthopaedics 4(4), pp. 600-604. pdf Lee, P.et al. 2016. Actovegin eguals performance enhancing drug doping: fact or fiction. Journal of Tissue Science and Engineering 7(3), article number: 179. (10.4172/2157-7552.1000179) pdf Ashlin, T.et al. 2014. The anti-atherogenic cytokine interleukin-33 inhibits the expression of a disintegrin and metalloproteinase with thrombospondin motifs-1,-4 and-5 in human macrophages: Requirement of extracellular signal-regulated kinase, c-Jun N-terminal kinase and phosphoinositide 3-kinase signaling pathways. The International Journal of Biochemistry & Cell Biology 46, pp. 113-123. (10.1016/j.biocel.2013.11.008) pdf Ashlin, T. G., Kwan, A. P. L. and Ramji, D. P. 2013. Regulation of ADAMTS-1, -4 and -5 expression in human macrophages: differential regulation by key cytokines implicated in atherosclerosis and novel synergism between TL1A and IL-17. Cytokine 64(1), pp. 234-242. (10.1016/j.cyto.2013.06.315) pdf Salter, R.et al. 2011. The expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 in human macrophages is inhibited by the anti-atherogenic cytokine transforming growth factor-β and requires Smads, p38 mitogen-activated protein kinase and c-Jun. The International Journal of Biochemistry & Cell Biology 43(5), pp. 805-811. (10.1016/j.biocel.2011.02.005) Salter, R.et al. 2010. ADAMTS proteases: key roles in atherosclerosis?. Journal of Molecular Medicine 88(12), pp. 1203-1211. (10.1007/s00109-010-0654-x)