Dual Action of Zinc in Bone and Vascular Calcification

Abstract

Osteogenic calcification is a normal physiological process in bone tissue, anywhere else like the blood vessel, it is a pathological process which is so‐called calcification paradox. The retarded skeletal growth in animals and man is the major sign of zinc inadequacy, which implies the involvement of zinc in osteogenic calcification.Our previous studies showed that inadequate zinc level in osteoblasts decreased osteogenic activities by decreasing extracellular matrix calcification, mainly through the inhibition of alkaline phosphatase (ALP) expression and activity, and by down‐regulation of osteoblast differentiation marker genes (osteopontin, osteocalcin and collagen type I), which is regulated through the reduced and delayed expression of bone‐specific transcription factor Runx2. Therefore, it seems zinc can be a stimulator in bone formation which includes osteogenic bone matrix calcification.Meanwhile, there is emerging evidence that zinc can protect against vascular damage and therefore may decrease the incidence of atherosclerotic plaque calcification. Our recent study using rat aortic smooth muscle cell line (A7r5) and rat primary vascular smooth muscle cells (pVSMC) showed that inadequate zinc level in VSMCs increased VSMC calcification and this calcification is paralleled with VSMC apoptotic pattern, rather than osteogenic calcification mode. In mice study using atherosclerotic model (ApoE null mouse), zinc deficiency promotes aorta Ca and P deposition (vascular calcification), while it decreases Ca and P contents in femur (bone calcification). The findings from our in vitro (osteoblasts and VSMCs) and in vivo (atherosclerotic ApoE null mouse) studies suggest that zinc may have a reciprocal role for calcification in bone (hard tissue) and blood vessel (soft tissue). It can be suggested that zinc may have a potential for therapeutic strategy for atherosclerosis as well as osteopoprosis, both of which involve the process of calcification.Support or Funding Information(Supported by the National Research Foundation of Korea, NRF‐2011‐0014535)