2002; Gerstenfeld 2003b). They are referred to as positive acute-phase et al., proteins and are secreted by macrophages, inflammatory cells and also cells of mesenchymal origin that are found in the periosteum (Wang 2004). The et al., function of these cytokines is to promote chemotaxis, thereby attracting other inflammatory cells to the site of injury. This mechanism stimulates extracellular matrix synthesis, angiogenesis and the recruitment of endogenous fibrogenic cells to the affected area. There is peak concentration of these proteins within the first 24 hours of the fracture occurring, followed by a drop in levels during the period of cartilage formation. Cytokine quantities are later restored, and become markedly increased again during the remodelling phase (Gerstenfeld 2003a; et al., Wang 2004). et al., The formation and remodelling of endochondral bone is regulated by cytokines (Barnes 1999). For example, TNF- stimulates the migration of MSCs, et al., evoking apoptosis of hypertrophic chondrocytes and stimulating osteoclastic activity. Indeed, absence of TNF- causes delayed resorption of mineralised cartilage, thereby inhibiting bone formation. Levels of IL-1, IL-6 and TNF- are increased again during fracture callus reshaping in the later stages of fracture healing and remodelling (Tsiridis 2007). et al., Transforming Growth Factor Beta (TGF-) There are many members of the TGF- superfamily, consisting of numerous growth and differentiation factors. More than 30 TGF- superfamily members
2002; Gerstenfeld et al., 2003b). They are referred to as positive acute-phase proteins and are secreted by macrophages, inflammatory cells and also cells of mesenchymal origin that are found in the periosteum (Wang et al., 2004). The function of these cytokines is to promote chemotaxis, thereby attracting other inflammatory cells to the site of injury. This mechanism stimulates extracellular matrix synthesis, angiogenesis and the recruitment of endogenous fibrogenic cells to the affected area. There is peak concentration of these proteins within the first 24 hours of the fracture occurring, followed by a drop in levels during the period of cartilage formation. Cytokine quantities are later restored, and become markedly increased again during the remodelling phase (Gerstenfeld et al., 2003a; Wang et al., 2004). The formation and remodelling of endochondral bone is regulated by cytokines (Barnes et al., 1999). For example, TNF- stimulates the migration of MSCs, evoking apoptosis of hypertrophic chondrocytes and stimulating osteoclastic activity. Indeed, absence of TNF- causes delayed resorption of mineralised cartilage, thereby inhibiting bone formation. Levels of IL-1, IL-6 and TNF- are increased again during fracture callus reshaping in the later stages of fracture healing and remodelling (Tsiridis et al., 2007). Transforming Growth Factor Beta (TGF-) There are many members of the TGF- superfamily, consisting of numerous growth and differentiation factors. More than 30 TGF- superfamily members
PhDthesis_ANDREW_SLOAN.docx