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Osteosarcoma (OS) originates from bone-forming mesenchymal cells and represents one of the primary bone tumours. It is the most common primary bone tumour in dogs and man. The characterization of an appropriate natural disease animal model to study human OS is essential to elucidate the pathogenesis of the disease. This study aimed to validate canine OS as a model for the human disease by evaluating immunohistochemically the expression of markers known to be important in human OS. The immunohistochemical panel included vimentin, alkaline phosphatase (ALP), desmin, S100, neuron-specific enolase (NSE), runt-related transcription factor 2 (Runx2) and bone morphogenetic protein 4 (BMP4). Immunohistochemistry was conducted on formalin-fixed, paraffin wax-embedded tissue sections from 59 dogs with confirmed primary OS. Vimentin, ALP, Runx2 and BMP4 were highly expressed by all tumours, while desmin, S100 and NSE were expressed variably. The findings were similar to those described previously for human OS and suggest that canine OS may represent a useful model for the study of the human disease.

Bone is considered to be a feature of higher vertebrates and one of the features that was required for the movement from water onto land. But there are a number of evolutionarily important species that have cartilaginous skeletons, including sharks. Both bony and cartilaginous fish are believed to have a common ancestor who had a bony skeleton. A number of factors and pathways have been shown to be involved in the development and maintenance of bony skeleton including the Wnt pathway and the parathyroid hormone gene family. The study of these pathways and factors in cartilaginous animals may shed light on the evolution of the vertebrate skeleton.

This review lecture will examine the available evidence about the roles of PTH and PTHrP in regulating mineral homeostasis during fetal development, and will demonstrate that these two hormones maintain interlocking, complementary, and at times overlapping roles. Each is unable to make up for loss of the other hormone. PTHrP is expressed within the growth plate, directs endochondral bone formation, and determines the fate of chondrocytes before bone formation can be initiated. It is expressed in placenta and is present at high levels in the fetal circulation. It stimulates placental calcium (and possibly magnesium) transfer, and raises blood minerals levels above ambient maternal values in order to effect mineralization of the skeleton. It does not upregulate in response to absence of PTH or hypocalcemia, and so its secretion may be regulated autonomously or in response to placental signals. Its actions on endochondral bone development require the PTH/PTHrP receptor (PTH1R); its actions on placental calcium transfer appear to require a midmolecular receptor; its actions to raise the blood calcium above the maternal level may require both receptors. PTH is expressed in fetal parathyroids and placenta. Despite circulating at low levels it has a more dominant effect than PTHrP in regulating the blood calcium and ensuring adequate mineralization of the skeleton by term. It probably does not affect the cartilaginous stages of endochondral bone development although it may influence bone formation in the steps that occur after the apoptosis of hypertrophic chondrocytes. Unlike PTHrP, it increases with fetal hypocalcemia, but its secretion is constrained by the calcium sensing receptor to maintain the adult calcium level, well below what the fetus normally achieves. PTH does have the ability to stimulate placental calcium transfer but whether this occurs normally or only in response to abnormal conditions (such as absence of PTHrP, or pharmacological treatment with PTH) remains unknown. Absence of PTH disrupts expression of calciotropic and other cation transporter genes within the placenta. All of the known actions of PTH require normal expression of the PTH1R. This article is part of a Special Issue entitled ECTS 2011. Disclosure of interest: None declared.