Longitudinal growth is the key characteristic that distinguishes children from adults. Growth is regulated in the growth plates, which are layers of cartilage located at the ends of the long bones.... Show moreLongitudinal growth is the key characteristic that distinguishes children from adults. Growth is regulated in the growth plates, which are layers of cartilage located at the ends of the long bones. The cartilage cells are called chondrocytes and go through a coordinated program of proliferation, maturation, hypertrophic differentiation, apoptosis and replacement by bone. This process is called endochondral bone formation. A complex network of hormones (endocrine regulators) is involved in this process. The mechanism of actions of these hormones is not completely understood. A possible mechanism of action is the interaction of systemic hormones with locally produced growth factors (paracrine regulators), like the Parathyroid Hormone (PTH) related Peptide (PTHrP) and its receptor, the type 1 PTH/PTHrP receptor (PTHR1). PTHrP and PTHR1 are among the key regulators in the process of endochondral bone formation. The working mechanism of PTHrP signalling, alone or in combination with other growth factors or systemic hormones, in endochondral bone formation is not completely understood. In this thesis, we have further addressed the actions of PTHrP in the complex network of endocrine and paracrine regulation of endochondral bone formation. Show less
