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Secreted Phosphoprotein 24 is a Biomarker of Mineral Metabolism

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Abstract

The 24 kD form of secreted phosphoprotein (SPP-24), a cytokine-binding bone matrix protein with various truncated C-terminal products, is primarily synthesized by the liver. SPP-24 shares homology with fetuin-A, a potent vascular and soft tissue calcification inhibitor and SPP-24 is one component of calciprotein particles (CPPs), a circulating fetuin–mineral complex. The limited molecular evidence to date suggests that SPP-24 may also function as an inhibitor of bone formation and ectopic vascular calcification, potentially through bone morphogenic protein 2 (BMP-2) and Wnt-signaling mediated actions. The C-terminal products of SPP-24 bind to BMP-2 and attenuate BMP-2-induced bone formation. The aim of this study was to assess circulating SPP-24 in relation to kidney function and in concert with markers of mineral metabolism in humans. SPP-24 was measured in the serum of total of 192 subjects using ELISA-based measurements. Subjects were participants of one of two cohorts: (1) mGFR Cohort (n = 80) was participants of a study of measured GFR (mGFR) using inulin urinary clearance, recruited mostly from a chronic kidney disease clinic with low-range kidney function (eGFR 38.7 ± 25.0 mL/min/1.73 m2) and (2) CaMOS Cohort (n = 112) was a subset of randomly selected, community-dwelling participants of year 10 of the Canadian Multicentre Osteoporosis Study with eGFR in the normal range of 75.0 ± 15.9 mL/min/1.73 m2. In the combined cohort, the mean SPP-24 was 167.7 ± 101.1 ng/mL (range 33.4–633.6 ng/mL). The mean age was 66.5 ± 11.3, 57.1% female and mean eGFR (CKD-EPI) was 59.9 ± 27.0 mL/min/1.73 m2 (range 8–122 mL/min/1.73 m2). There was a strong inverse correlation between SPP-24 and eGFR (R = − 0.58, p < 0.001) that remained after adjustment for age. Following adjustment for age, eGFR, and sex, SPP-24 was significantly associated with phosphate (R = − 0.199), PTH (R = 0.298), and the Wnt-signaling inhibitor Dickkopf-related protein 1 (R = − 0.156). The results of this study indicate that SPP-24 is significantly altered by kidney function and is the first human data linking levels of SPP-24 to other biomarkers involved in mineral metabolism. Whether there is a role for circulating SPP-24 in bone formation and ectopic mineralization requires further study.

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Acknowledgements

The authors wish to thank the staff of the Kingston CaMOS center for obtaining the demographic and radiological data from the study subjects in the CaMOS Cohort. Also, they thank Claudie Berger of the coordinating CaMOS office at McGill University (Montreal), for facilitating access to the relevant biochemical data in the central CaMOS database.

Funding

Funding was provided by CaMOS, CIHR (Grant Nos. 201003MOP, 201711CGV).

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Authors and Affiliations

  1. Department of Biomedical and Molecular Sciences, Queen’s University, 3048C Etherington Hall, Kingston, ON, K7L 3V6, Canada

    Mandy E. Turner, Sarah M. Taylor, Kathryn Neville, Michael A. Adams, Tassos Anastassiades & Rachel M. Holden

  2. Department of Medicine, Queen’s University, Kingston, ON, K7L 3V6, Canada

    Christine A. White, Karen Rees-Milton, Tassos Anastassiades & Rachel M. Holden

  3. KGH Research Institute, Kingston Health Sciences Centre, Kingston, ON, K7L 3V6, Canada

    Wilma M. Hopman

  4. Department of Public Health Sciences, Queen’s University, Kingston, ON, K7L 3V6, Canada

    Wilma M. Hopman

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Correspondence to Rachel M. Holden.

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Mandy E. Turner, Christine A. White, Sarah M. Taylor, Kathryn Neville, Karen Rees-Milton, Wilma M. Hopman, Michael A. Adams, Tassos Anastassiades, Rachel M. Holden declare that they have no conflict of interest.

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Turner, M.E., White, C.A., Taylor, S.M. et al. Secreted Phosphoprotein 24 is a Biomarker of Mineral Metabolism. Calcif Tissue Int 108, 354–363 (2021). https://doi.org/10.1007/s00223-020-00783-3

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