Professor Rebecca S. Mason and her group study bone and mineral metabolism, particularly cellular and molecular physiology of bone formation and resorption and mineral ion regulation. We have also shown that some bone-related hormones such as vitamin D and parathyroid hormone-related peptide are important in skin cell physiology.

Current projects in bone and mineral include studies on the mechanisms of corticosteroid-induced osteoporosis, bone cell actions of phytoestrogens and characterisation of a novel phosphate regulating hormone. The area of skin research interest is mechanisms of skin cell protection from ultraviolet irradiation and ways of enhancing this.

Hypophosphatemic factor in oncogenic osteomalacia
AE Nelson, M Mirams, E Martin, RS Mason
(collaborators: BG Robinson, Dept of Medicine; R. Baxter, Kolling Institute, RNSH, Ingrid Holm, Boston Childrens Hospital; R Redell, A Chang, Children's Medical Research Institute, Sydney; O Ljunggren, Department of Internal Medicine, University Hospital, Uppsala, Sweden)

Oncogenic osteomalacia is a condition of renal phosphate wasting causing impaired bone mineralization in the presence of a connective tissue tumour. A factor was identified which inhibits renal phosphate uptake, and which is secreted into the culture medium by a cell line derived in this Laboratory from such a tumour. Although the factor was shown to have some properties similar to parathyroid hormone, it was shown not to be either parathyroid hormone or parathyroid hormone-related peptide or a new putative phosphate regulator, stanniocalcin. A tumour cell cDNA library has been prepared and strategies to screen this library are being developed. Experiments to characterise the phosphate-active factor indicate that it is stable to heat and trypsin treatment. A purification strategy using HPLC is being pursued with some success. This work is likely to lead to the identification of a new phosphate regulating hormone which is overproduced by this kind of tumour.

Phytoestrogens and bone cell function
MM Muir, D Siva, D Dai, RS Mason
(collaborators: D Brown, A Husband, Novogen Pty Ltd)

Sex steroid hormones, particularly estrogens are important for the maintenance of bone mass. At the menopause in females, circulating estrogen concentrations decrease and bone loss results. There is evidence that estrogen-like compounds from plants such as clover and soy are able to maintain bone mass under some circumstances but how this effect is achieved at a cellular level is not clear. The studies are examining the effects of these compounds on bone cell function, activity and lifespan. It is possible that phyto-estrogens belong to a class of compounds called Selective Estrogen Response Modifiers (SERMS). These compounds have estrogenic effects at some sites, but anti-estrogenic effects at others. They are potentially of use in preventing or treating osteoporosis, possibly without some of the adverse effects on uterine or breast tissue that is associated with normal estrogen replacement.

Role of Vitamin D and other compounds in protection of skin cells from UV
R Gupta, M Smith, RS Mason
(collaborators: GM Halliday, A Jones, Department of Medicine (Dermatology); GP Moore, C Gordon-Thomson, Department of Biological Sciences, University of Western Sydney; GH Posner, Department of Organic Chemistry, Johns Hopkins University, Baltimore, USA)

Our group has shown that vitamin D compounds, which are well known to be made in skin, may have an important physiological function in skin to protect skin cells from the damaging effects of UV radiation. Cell death, mainly by apoptosis after UV exposure, is significantly reduced in both human keratinocytes (epidermal cells) and melanocytes (pigment cells) after treatment with vitamin D metabolites. The work examines some likely mechanisms of action of the vitamin D compounds and the possible involvement of other skin cell-produced compounds which may potentiate this effect.

Glucocorticoids and Bone
D Siva, MM Muir, R S Mason
(collaborator: JP Seale, Department of Pharmacology)

While glucocorticoids are important in promoting the differentiated function of bone cells, when given in pharmacologic doses, their effect is to upset the normal balance between bone formation and resorption with nett bone loss a result. Studies in this laboratory have pointed to two important functional consequences of glucocorticoid treatment of bone cells.

Proliferation of early pre-osteoblasts is reduced, whilst the cells undergo accelerated maturation, indicated by high alkaline phosphatase activity. Several glucocorticoid analogues used in respiratory medicine were tested for their potency in the bone formation model. In general, the order of potencies of the glucocorticoids in the bone model is similar to that described using immune cell models, though for some glucocorticoids, much higher doses are required for effects on bone cell function than on immune cell function. The next phase of the study is to examine how glucocorticoids affect the development and activity of bone-resorbing cells, osteoclasts