Challenges in establishing animal models for studying osteoimmunology of hypoparathyroidism

Abstract

Hypoparathyroidism is a relatively rare human and veterinary disease characterized by deficient or absent production of parathyroid hormone (PTH). PTH is known as a classical regulator of calcium and phosphorus homeostasis. Nevertheless, the hormone also appears to modulate immune functions. For example, increased CD4:CD8 T-cell ratios and elevated interleukin (IL)-6 and IL-17A levels were observed in patients with hyperparathyroidism, whereas gene expression of tumor necrosis factor-α (TNF-α) and granulocyte macrophage-colony stimulating factor (GM-CSF) was decreased in patients with chronic postsurgical hypoparathyroidism. Various immune cell populations are affected differently. So, there is a need for validated animal models for the further characterization of this disease for identifying targeted immune-modulatory therapies. In addition to genetically modified mouse models of hypoparathyroidism, there are surgical rodent models. Parathyroidectomy (PTX) can be well performed in rats-for pharmacological and associated osteoimmunological research and bone mechanical studies, a large animal model could be preferable, however. A major drawback for successfully performing total PTX in large animal species (pigs and sheep) is the presence of accessory glands, thus demanding to develop new approaches for real-time detection of all parathyroid tissues.

Keywords: PTH; T cells; TNF-α; animal models; bone; interleukins.