Longitudinal growth takes place at the growth plate (GP), or physis- a highly organized structure within the distal ends of long bones. Elongation of bone is established by the process of enchondral ossification, where a synchronized sequence of chondrocyte differentiation and proliferation is regulated by means of endocrine, paracrine and autocrine mechanisms. From a clinical point of view, a reduction or increase of relevant hormones (eg growth hormone, thyroid hormone, sex steroids, glucocorticoids) is accompanied by distinct pictures of growth failure or excess. At the level of the growth plate, the mechanisms behind these growth disorders are poorly understood, or concepts have derived from animal models, mainly rodents. While the local actions of growth stimulating factors like GH and IGF-I have been well documented, at least in animal models- the mode of action of skeletal maturation/ closure of the growth plate during puberty is obscure. Investigation of growth plate tissue has mainly been performed in rodents (which do not close their GPs completely), and human material is very limited.
In previous work our group has investigated the presence of ERs, matrix composition and the role of matrix degrading encymes (metalloproteinases) in human childhood and adolescent growth plates in vivo by immunohistochemistry. We have developed a porcine in vitro model of growth plate chondrocytes. The primary focus of our research is the action of GH and IGF-I on chondrocyte proliferation and differentiation and the role of local and systemic factors on local mineralization processes.
Methods & Techniques
Tissue preparation, cell isolation, cell sorting, cell culture, immunohistochemistry, immunocytochemistry, quantitative RT-PCR, Immunoblot.
Haeusler G, Walter I, Helmreich M, Egerbacher M: Localization of matrix metalloproteinases, (MMPs) their tissue inhibitors, and vascular endothelial growth factor (VEGF) in growth plates of children and adolescents indicates a role for MMPs in human postnatal growth and skeletal maturation. Calcif Tiss Int 76: 326-335, 2005
Albrecht C, Helmreich M, Tichy B, Marlovits S, Plasenzotti R, Egerbacher M, Haeusler G: Impact of 3D-culture on the expression of differentiation markers and hormone receptors in growth plate chondrocytes as compared to articular chondrocytes. Int J Molec Med 23: 347-355, 2009
Schlegel W, Halbauer D, Raimann A, Albrecht C, Scharmer D, Sagmeister S, Helmreich M, Häusler G, Egerbacher M: IGF-I expression patterns and regulation in growth plate chondrocytes. Mol Cell Endocrinol 327: 65-71, 2010
Gleiss A, Lassi M, Blümel P, Borkenstein M, Kapelari K, Mayer M, Schemper M, Häusler G: <//span>Austrian height and body proportion references for children aged 4 to under 19 years. Ann Hum Biol 40: 324-332, 2013
Schlegel W, Raimann A, Halbauer D, Scharmer D, Sagmeister S, Wessner B, Helmreich M, Haeusler G, Egerbacher M:.<//span>Insulin-like growth factor I (IGF-1) Ec / Mechano growth factor – a splice variant of IGF-1 within the growth plate. PLoS One 8: e76133,<//span><//span> 2013