Given a constant IGF concentration, as the receptor density increases, so the total number of IGF-IR receptor complexes will clearly increase. There is also the possibility that cells may spatially vary their expression of cell surface receptors throughout the tissue, which adds another layer of complexity. This is an important area and will later on be investigated in a parametric study. Receptor behavior is complex. IGF-IR has significantly higher Mepiroxol binding preference for IGF-I and �CII compared to insulin, whereas IGF-IIR only preferentially binds IGF-II. In comparison to IGFBPs 1�C6, IGFBP-7 lacks the important ternary structure required for binding IGFs with high affinity, but has the capability of binding to insulin and subsequently inhibit insulin binding to the insulin receptor. Although IGFBP-7 has been identified in human biological fluid, its concentration is too small to detect in human cartilage, and so is not explicitly considered in our model. The insulin receptor primarily regulates cell metabolic functions. Both IGF-IR and insulin receptors are usually tyrosine kinase Ginsenoside-Ro homodimers, but IGF-IR-insulin heterodimers may form. Hybrid receptors formed by IGF-IR and IR bind to IGF-I with at least 50-folder higher affinity than insulin irrespective of the splice variant. Homoand hetero-dimerisation of receptors is not considered here. While much is known about the individual components making up the IGF system, it still remains unclear how these components 
act together as an integrated system within a tissue. Indeed, it is likely that a ‘systems approach’is required for the development of more efficacious drug therapies. Our previous studies of cartilage have been particularly focussed on the IGF-I mediated cartilage ECM biosynthesis via IGF-IR. In this study, to achieve a system level of understanding of how tissues regulate their exposure to growth factors and so maintain normal tissue homeostasis and biological functions, we have developed a computational model of IGF system in cartilage involving IGF-I, IGF-II, insulin, IGF-IR, IGF-IIR and IR. Our aim is to identify the critical model variables for potentially controlling IGF signaling homeostasis based on a sensitivity analysis for the system. It is expected that the cartilage model developed here could be generalized further and applied to a range of different tissues in health and disease. Recently, more newly established rES cells are derived from fertilized embryos. Parthenogenetically activated oocytes or embryos are subjected to artificial stimuli to initiate embryonic development without fertilization process or incorporation of sperm chromosomes. These parthenotes possess chromosomes entirely of the maternal origin and fail to develop to term due to a lack of paternal gene expressions or normal genomic imprinting. Similar to f-rES cells, parthenote-derived rES cells can continuously proliferate in vitro, retain self-renewal capacity without differentiation, and also differentiate into cell lineages of the three germ layers both in vitro and in vivo. With these properties, p-rES cells have been proposed and proved to be useful in ameliorating or completely eliminating the risk of immunological rejection after cell transplantation. Recently, proteomic analyses have been performed to monitor the global protein expression and post-translational modifications in mouse ES cells, and to determine the protein expression profiles in mouse, monkey, and human ES cells undergoing chemically induced differentiation. So far, no authentic germline transmissible rES cell lines were reported and the molecular mechanisms superimposing distinct characteristics onto the f-rES and p-rES cells are largely unknown.