Osteoblast Cultures: A Valuable Tool for the Study of Hypophosphatemic Vitamin D- Resistant Rickets

Bone matrix formation and mineralization is a complex process which is under the control of the osteoblasts and nearby osteoid osteocytes. Impaired bone mineralization (osteomalacia) can result from alterations in the bone cell environment and/ or from abnormalities in the function of the bone-forming cells. Because of the methods available, most identified forms of osteomalacia have been related to disturbances in mineral or vitamin D metabolism. However, with the recent advances in cell biology, methods have been developed for osteoblast isolation. The isolated cells, provided they retain their differentiated phenotype in culture, offer a powerful tool for investigating the properties and functional responsiveness of osteoblasts and therefore for assessing intrinsic defects of the osteoblast function associated with genetic bone diseases. In addition, the availability of animal models closely resembling the human disorders has allowed more direct investigation of the pathophysiology of these disorders. Studies will be described in this chapter that illustrate the suitability of an animal model, the hypophosphatemic (Hyp) mouse and the usefulness of osteoblast cultures for investigating the pathogenesis of human vitamin D-resistant rickets (VDRR). Data will be presented which support the view that the osteoblast is an important target for the Hyp (and VDRR) mutation. Conceivably, methods will be developed in the future for isolating homogenous populations of osteoblasts from human origin that will allow direct evaluation of the function of osteoblasts from VDRR patients.