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A new perspective on the function of Tissue Non-Specific Alkaline Phosphatase: from bone mineralization to intra-cellular lipid accumulation

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Abstract

Tissue-nonspecific alkaline phosphatase (TNAP) is one of four isozymes, which include germ cell, placental and intestinal alkaline phosphatases. The TNAP isozyme has 3 isoforms (liver, bone and kidney) which differ by tissue expression and glycosylation pattern. Despite a long history of investigation, the exact function of TNAP in many tissues is largely unknown. Only the bone isoform has been well characterised during mineralization where the enzyme hydrolyses pyrophosphate to inorganic phosphate, which combines with calcium to form hydroxyapatite crystals deposited as new bone. The inorganic phosphate also increases gene expression of proteins that support tissue mineralization. Recent studies have shown that TNAP is expressed in preadipocytes from several species, and that inhibition of TNAP activity causes attenuation of intracellular lipid accumulation in these and other lipid-storing cells. The mechanism by which TNAP stimulates lipid accumulation is not known; however, proteins that are important for controlling phosphate levels in bone are also expressed in adipocytes. This review examines the evidence that inorganic phosphate generated by TNAP promotes transcription that enhances the expression of the regulators of lipid storage and consequently, that TNAP has a major function of lipid metabolism.

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Funding

WF funding: National Research Foundation (NRF) of South Africa (Grant 118565). NC funding: The National Research Foundation of South Africa (Grant 93999), The National Health Laboratory Services Research Trust (Grant 94311) and University of the Witwatersrand Faculty of Health Sciences Research Committee (Grant 4875crowther). ‘Any opinion, finding, conclusion or recommendation expressed in this material is that of the authors and the NRF does not accept any liability in this regard’.

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  1. Cara-Lesley Bartlett and Eleanor Margaret Cave have contributed equally to this manuscript.

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  1. Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa

    Cara-Lesley Bartlett & William Frank Ferris

  2. Department of Chemical Pathology, University of the Witwatersrand Faculty of Health Sciences, Johannesburg, South Africa

    Eleanor Margaret Cave & Nigel John Crowther

  3. Department of Chemical Pathology, National Health Laboratory Service, Johannesburg, South Africa

    Nigel John Crowther

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C-LB and EMC involved in writing a portion of the first draft. NJC involved in adding some additional information and editing the final draft. WFF contributed to rewriting the manuscript, adding additional information, the final edits and manuscript submission.

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Bartlett, CL., Cave, E.M., Crowther, N.J. et al. A new perspective on the function of Tissue Non-Specific Alkaline Phosphatase: from bone mineralization to intra-cellular lipid accumulation. Mol Cell Biochem 477, 2093–2106 (2022). https://doi.org/10.1007/s11010-022-04429-w

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