B3074 - Exploration of functional links between sclerostin and phosphate metabolism - 17/07/2018

B number: 
B3074
Principal applicant name: 
Jon Tobias | University of Bristol (United Kingdom)
Co-applicants: 
Dr Jie Zheng, Dr Celia Gregson, Prof George Davey-Smith, Dr Ben Faber
Title of project: 
Exploration of functional links between sclerostin and phosphate metabolism
Proposal summary: 

The level of phosphate in the bloodstream is regulated by a number of hormonal factors including klotho. These are stimulated in conditions such as impaired kidney function, which causes a rise in circulating phosphate levels. It has recently been found that when kidney function is impaired, another protein, sclerostin, is also increased. Sclerostin, which has an important role in regulating the amount of bone formed, is the target for a new treatment being developed for osteoporosis, acting by blocking sclerostin activity. Combined with other circumstantial evidence, we propose that important functional relationships exist between the hormones that regulate phosphate levels and sclerostin, which contribute to the decline in bone density seen in renal impairment. This hypothesis will be examined by exploring relationships between klotho levels, measured as part of this proposal, and sclerostin, in a sample of ALSPAC mothers.

Impact of research: 
Characterising the relationship between klotho and sclerostin will help in understanding the pathogenesis of osteoporosis associated with CKD, leading to new opportunities for treatment. If sclerostin is found to be related to klotho levels, this may raise safety concerns over sclerostin antibody treatment being developed for osteoporosis, given the link between phosphate metabolism and vascular calcification.
Date proposal received: 
Wednesday, 7 March, 2018
Date proposal approved: 
Thursday, 8 March, 2018
Keywords: 
Physiology, Bone disorders - arthritis, osteoporosis, ELISA, Biological samples -e.g. blood, cell lines, saliva, etc.