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    Genes involved in bone mass regulation

    Osteoporosis is mainly down to how the body regulates bone mass, subtracting more bone than it adds as people get older. But what is known about the genes that play a role in osteoporosis? Well many genes have been identified that have an influence on the metabolism of calcium and in bone mass turnover regulation.

    Genes that may be involved in osteopenia related regulation

    There are a large number of genes known to be involved in processes that may have an impact on osteoporosis; These are split up into many categories depending upon their role.

    1.Osteoblast regulatory factors eg. Alox 12 and 15, Sclerostin, Lipoprotein-related receptors 5 and 6.
    2.Bone Matrix components and degradative enzymes eg. Alpha HS2 glycoprotein, osteocalcin.
    3.Cytokines and receptors eg. Interleukin-6, Tumor necrosis factor.
    4.Hormones and receptors eg. Ardrogen receptor, vitamin D receptor.
    5.Osteoclast related genes eg. cathepsin K, osteoprotegerin.
    6.Others eg. Apolipoprotein E, Klotho

    Although many many genes have been linked with a role in bone mass regulation, for the majority little is known about their roles in osteoporosis and if they play a part in bone mass deterioration at all. However some of these genes have been widely studied and their mechanisms better understood.

    Lipoprotein receptor-related proteins

    wnt signalling helps to regulate many biological development processes including those of osteoblast differentiation. The Lipoprotein receptor-related 5 and 6 genes code proteins that are able to act as receptors for canonical wnt signaling. The Lipoprotein receptor-related 5 protein forms a complex with other proteins. Scientific linkages studies on the human diseases, HBM syndrome and OPPS have shown that the Lipoprotein receptor-related 5 pathway is one of the key regulators of bone mass.

    Transforming Growth factor B1

    The TGFB1 gene encodes a protein that is abundant in bone and has been demonstrated to influence the in vitro function of osteoblast and osteoclast.

    Sclerostin

    The sclerostin gene encodes a knot-containing protein. It was identified as playing a role in bone mass reglation through studies on van Buchem disease and Sclerosteosis.

    In addition to the above many genes have been linked to bone mass regulation and may therefore play a role in osteoporosis. Much research is presently being carried out of the genetics that may influence the condition. It is thought that a better understanding of the mechanisms that underlie bone mass regulation may one day lead to better medical treatment of osteoporosis.

    References
    Ralston and Crombrrugghe. Genetic Regulation of Bone Mass and Susceptibility to Osteoporosis.
    Genes and development. 20;2492-2506 (2006)
    Liu et al. Molecular studies of identification of genes for osteoporosis. J. Endocrinol. 177; 147-196 (2003).