Systems Biology of Bone

The Systems Biology of Bone team, headed by Vijay Yadav, uses mice as a model organism to identify the genes and their interactions that determine bone mass.

Vijay's team generates and studies animals with abnormal bone mass and investigates the gene networks that determine these changes. Their long-term aim is to identify key genes and gene networks in vertebrates that regulate bone cell functions.

[Patrick Siemer, Wikimedia Commons]


Bone remodelling, a homeostatic function, is regulated by two major bone cell types - osteoblasts and osteoclasts. Osteoblasts make new bone, while osteoclasts degrade the pre-existing mineralized matrix or the old bone. This process ensures that we have a normal bone mass throughout the majority of our adult lives.

An imbalance in the bone remodelling process results in a low bone density or osteoporosis, a major disease of the aging human population that affects millions of people throughout the world. The main problem in treating osteoporosis today is that although there are several therapies that stop degradation of bone there exists only one therapy - intermittent injection of Parathyroid hormone - to increase bone mass in humans. Therefore we need to advance our understanding of bone formation in order to provide alternative or better anabolic therapies for people with low bone density or osteoporosis.

The Systems Biology of Bone group uses disruption of genes in mouse, genomic, and proteomic approaches to unravel the factors that regulate bone remodelling. The bones in our body are like houses. A house is constantly deteriorating due to external factors, such as sunlight and rain, internal factors such as rusting or woodworm. In the same way our bones can deteriorate due to factors that originate within and outside the bone. For example, alterations in the levels and/or action of certain cytokines or hormones can lead to changes in bone mass. The best example of this phenomenon is the loss of oestrogen - an ovary-derived hormone - after menopause, which can result in increased bone remodelling and can lead ultimately to osteoporosis. This fact underscores that systemic influences or molecules originating in other organs are central to the regulation of bone mass. We aim to identify some of these factors that regulate bone remodelling through the use of high-throughput genomic and proteomic approaches.

Our primary aim is to develop new mouse models for bone diseases to allow the identification of key genes and/or pathways for a systematic analysis of the process of bone remodelling and the effect of factors originating in other organs. This may help to further the understanding of the biology of bone and ultimately identify new targets for therapeutic intervention.

Selected publications

  • Signaling through the M(3) muscarinic receptor favors bone mass accrual by decreasing sympathetic activity.

    Shi Y, Oury F, Yadav VK, Wess J, Liu XS, Guo XE, Murshed M and Karsenty G

    Cell metabolism 2010;11;3;231-8

  • Pharmacological inhibition of gut-derived serotonin synthesis is a potential bone anabolic treatment for osteoporosis.

    Yadav VK, Balaji S, Suresh PS, Liu XS, Lu X, Li Z, Guo XE, Mann JJ, Balapure AK, Gershon MD, Medhamurthy R, Vidal M, Karsenty G and Ducy P

    Nature medicine 2010;16;3;308-12

  • A serotonin-dependent mechanism explains the leptin regulation of bone mass, appetite, and energy expenditure.

    Yadav VK, Oury F, Suda N, Liu ZW, Gao XB, Confavreux C, Klemenhagen KC, Tanaka KF, Gingrich JA, Guo XE, Tecott LH, Mann JJ, Hen R, Horvath TL and Karsenty G

    Cell 2009;138;5;976-89

  • Dissociation of the neuronal regulation of bone mass and energy metabolism by leptin in vivo.

    Shi Y, Yadav VK, Suda N, Liu XS, Guo XE, Myers MG and Karsenty G

    Proceedings of the National Academy of Sciences of the United States of America 2008;105;51;20529-33

  • Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum.

    Yadav VK, Ryu JH, Suda N, Tanaka KF, Gingrich JA, Schütz G, Glorieux FH, Chiang CY, Zajac JD, Insogna KL, Mann JJ, Hen R, Ducy P and Karsenty G

    Cell 2008;135;5;825-37

  • Dynamic changes in mitogen-activated protein kinase (MAPK) activities in the corpus luteum of the bonnet monkey (Macaca radiata) during development, induced luteolysis, and simulated early pregnancy: a role for p38 MAPK in the regulation of luteal function.

    Yadav VK and Medhamurthy R

    Endocrinology 2006;147;4;2018-27

  • Prostaglandin F2alpha-mediated activation of apoptotic signaling cascades in the corpus luteum during apoptosis: involvement of caspase-activated DNase.

    Yadav VK, Lakshmi G and Medhamurthy R

    The Journal of biological chemistry 2005;280;11;10357-67

  • Identification of novel genes regulated by LH in the primate corpus luteum: insight into their regulation during the late luteal phase.

    Yadav VK, Muraly P and Medhamurthy R

    Molecular human reproduction 2004;10;9;629-39

  • Cloning of a buffalo (Bubalus bubalis) prostaglandin F(2alpha) receptor: changes in its expression and concentration in the buffalo cow corpus luteum.

    Verma-Kumar S, Srinivas SV, Muraly P, Yadav VK and Medhamurthy R

    Reproduction (Cambridge, England) 2004;127;6;705-15

  • Apoptosis during spontaneous and prostaglandin F(2alpha)-induced luteal regression in the buffalo cow (Bubalus bubalis): involvement of mitogen-activated protein kinases.

    Yadav VK, Sudhagar RR and Medhamurthy R

    Biology of reproduction 2002;67;3;752-9


No team members listed

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