ESPE Abstracts (2014) 82 WG1.1

Unravelling GH Actions on the Growth Plate and its Promotion of Linear Growth

Colin Farquharson

University of Edinburgh, Edinburgh, UK

The functional activities of growth plate chondrocytes are tightly controled to regulate the pace of linear growth. Simplistically, growth rate is determined by the number of cells within the proliferative zone which is regulated by their rate of proliferation and also their rate of differentiation into the hypertrophic phenotype. In turn, a strong positive correlation exists between the final hypertrophic cell volume and the rate of growth. Interruption and/or deregulation of this highly ordered sequence of events results in impaired bone growth and short stature which, in a significant number of children, is not rectified by catch-up growth. Inhibitors of growth can act both exogenously (e.g. physical trauma and pharmacological agents) or endogenously (e.g. altered autocrine/paracrine and systemic control). Examples of the latter include alterations to the GH/IGF1 axis which is recognised to be a key pathway in the regulation of bone growth. Whilst the growth promoting role of GH on linear bone growth is well accepted the relative contributions to post-natal growth of the direct or indirect effects of GH remain unclear. The GH indirect effects are via endocrine and/or local (growth plate cartilage) IGF-1 production. Various spontaneous mouse mutations in GH/IGF1 signalling have been informative. Also, the mouse genetic revolution with the creation of various transgenic and knock-out (inducible and tissue specific) strains of mice e.g. SOCS2 null mice, have helped us understand more fully the role of GH and IGF1 initiated pathways together with their negative feed-back loops and associated kinases and phosphatases in the linear bone growth process. Notwithstanding the direct effects of GH on growth plate chondrocytes it is likely that these two systems function in a highly coordinated manner to regulate growth plate function and linear bone growth. This presentation will summarise the current state of understanding and introduce emerging insights.

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