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These studies showed that neonatal cord blood contained high PTH-like activity although N-terminal immunoreactivity was absent. The bioactivity was related to the positive gradient of calcium across the placenta and the authors suggested that it was PTHrP that maintained this gradient. It had also been recognised for some time that some patients with malignancy developed hypercalcaemia with undetectable levels of PTH. Subsequently, a protein was purified from lung cancer cells that had similar biological properties to PTH but which was clearly different from PTH itself [30].

The Target Organs The principal target organs of PTH are bone and kidney. In bone, PTH has two main effects. Under physiological conditions, it promotes bone formation via receptors on the osteoblasts. Under circumstances of hypocalcaemia, PTH stimulates bone resorption in order to retrieve calcium from the large reservoir within bone so that normocalcaemia can be restored. There are very few receptors for PTH in osteoclasts and bone resorption occurs as a result of changes within the relationship between osteoblasts and osteoclasts.

A second transcription factor, Osterix, acts downstream of Runx2 in osteoblast differentiation. Osteoblasts can further differentiate into osteocytes that become embedded in the bone matrix or into lining cells on bone surfaces. Osteoblast Differentiation and Function Osteoblasts, bone-lining cells and osteocytes all arise from a multipotent precursor of mesenchymal origin that also gives rise to chondrocytes, adipocytes, myocytes and fibroblasts, most commonly called a mesenchymal stem cell [11] (fig.

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Cars


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