New face of an old enzyme: alkaline phosphatase may contribute to human tissue aging by inducing tissue hardening and calcification.
Tissue nonspecific alkaline phosphatase (AP) plays a well-known role in bone mineralization. This role was first suggested by a human AP deficiency disease, hypophosphatasia. Further studies with AP gene knockout mice have also suggested a role for AP in mineralization. However, AP is also expressed in other human tissues besides bone and cartilage, and this raises a question as to whether AP may also play a role in pathological mineralization such as dystrophic and vascular calcification. In vitro studies carried out in our laboratory indicate that a variety of cell types stably expressing membrane-bound AP can affect extracellular mineralization regardless of the tissue from which the cell lines originated (e.g. fibroblasts, vascular endothelial cells, or renal epithelial cells). This AP-mediated extracellular mineralization is both substrate/dependent and culture environment/dependent and may be consistent with a putative role for AP in pathological mineralization in tissues other than bone and cartilage. In this regard, it is interesting to note that high levels of AP are observed in vascular endothelia of small arterioles in brain and heart. It is probable that expression of AP in small arterioles of brain and heart may also contribute to the vascular hardening and calcification observed in humans. This in turn could be related to vascular aging, vascular disease, and the resultant weakening of and/or rupture of vessel walls.
Division of Periodontics, Faculty of Dentistry, University of Toronto.
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D000375:Aging / Q000502:physiology*; D000469:Alkaline Phosphatase / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002113:Calcification, Physiologic / Q000502:physiology; D002478:Cells, Cultured; D046508:Culture Techniques; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007014:Hypophosphatasia / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism; D051379:Mice; D008854:Microscopy, Electron; D010013:Osteogenesis Imperfecta / Q000503:physiopathology
D000469:Alkaline Phosphatase