birth. This was consistent with a low bone mass, osteopenia and abnormal osteoblastic function. Humans with NOG mutations can present frank skeletal and joint impairment, whilst NOG knockout mice die shortly after birth and have dense, deformed long bones, implicating the mediatory role of noggin (Brunet et 1998; Devlin 2003a). The rare genetic bone disease Fibrodysplasia al., et al., Ossificans Progressiva (FOP) is characterised by abnormal hallux development and progressive heterotopic endochondral ossification of the muscles. This disorder is due to a lack of expression of the NOG gene (Fontaine 2005). et al., Chordin The antagonist chordin (Chd) binds with BMP-2, BMP-4 and BMP-7 in a similar way to noggin, thereby antagonising the actions of BMP by blocking the binding action to its receptors. Chordin also has a role in embryonic development, especially in skeletogenesis, as high levels are expressed in cartilage and in the epiphyseal regions of developing long bones (Bostrom, 1998; Balemans and Van Hul, 2002; Marshall 2004). Expression of Chd has been found to be et al., in vitro inversely related to chondrocyte maturation and differentiation due to BMP inhibition and is considered to be a negative regulator of endochondral ossification. The secreted protein (TSG) is a cofactor that twisted gastrulation attaches to Chd, thus facilitating the inhibition of BMPs by sensitising binding. Twisted gastrulation can also act as an independent inhibitor, and levels are highest in the early stages of osteoblast differentiation (the preosteoblast stage) (Oelgeschlager 2003; Petryk 2005). et al., et al.,
birth. This was consistent with a low bone mass, osteopenia and abnormal osteoblastic function. Humans with NOG mutations can present frank skeletal and joint impairment, whilst NOG knockout mice die shortly after birth and have dense, deformed long bones, implicating the mediatory role of noggin (Brunet et al., 1998; Devlin et al., 2003a). The rare genetic bone disease Fibrodysplasia Ossificans Progressiva (FOP) is characterised by abnormal hallux development and progressive heterotopic endochondral ossification of the muscles. This disorder is due to a lack of expression of the NOG gene (Fontaine et al., 2005). Chordin The antagonist chordin (Chd) binds with BMP-2, BMP-4 and BMP-7 in a similar way to noggin, thereby antagonising the actions of BMP by blocking the binding action to its receptors. Chordin also has a role in embryonic development, especially in skeletogenesis, as high levels are expressed in cartilage and in the epiphyseal regions of developing long bones (Bostrom, 1998; Balemans and Van Hul, 2002; Marshall et al., 2004). Expression of Chd in vitro has been found to be inversely related to chondrocyte maturation and differentiation due to BMP inhibition and is considered to be a negative regulator of endochondral ossification. The secreted protein twisted gastrulation (TSG) is a cofactor that attaches to Chd, thus facilitating the inhibition of BMPs by sensitising binding. Twisted gastrulation can also act as an independent inhibitor, and levels are highest in the early stages of osteoblast differentiation (the preosteoblast stage) (Oelgeschlager et al., 2003; Petryk et al., 2005).
PhDthesis_ANDREW_SLOAN.docx