Zn deficiency induces calcification by regulating apoptosis rather than osteogenesis in vascular smooth muscle cells

Recent findings have shown that vascular and bone calcification share the same cell‐regulated process. While the positive effect of Zn on osteogenic calcification has been well studied, its role on vascular calcification remains obscure. This study investigated how Zn modulates calcification in vascular smooth muscle cells (SMC). Our findings showed that Zn deficiency promoted calcification in vitro and in vivo parallel with the apoptotic pattern as assessed by morphological examination and caspase‐3 activation of Zn‐deficient cultures. Zinc deficiency also caused a dramatic loss of SMC markers, SM22α and calponin, and this was much severe in high phosphate level, a condition favorable for calcification. Although the presence of the bone transcription factor Runx2 and osteopontin were detected on calcified cultures, the absence of alkaline phosphatase suggests that calcification in SMC was not matrix vesicle‐mediated but apoptosis‐regulated. Apoptosis was further confirmed by activation of pro‐apoptotic molecule JNK and this was stimulated by zinc deficiency. These data suggest that Zn deficiency promoted calcification in smooth muscle cells via apoptosis mechanism resulting in a concomitant phenotypic modulation, rather than regulating osteogenic calcification and provide a novel insight in the role of Zn to differentially regulate calcification in the pathogenesis of vascular diseases.