**4. Cell‐driven calcification: the example of vascular calcification**

In the last decade, some researchers have attempted to clarify the effects of high oxalate and crystal concentrations on the biology of renal tubular cells because the exact role of the tubu‐ lar cells in response to the influx of these potentially precipitating ions is still uncertain.

A role in the pathogenesis of Randall's plaques has also been suggested for interstitial cells capable of transdifferentiating along the bone lineage, leading to the hypothesis that neph‐ rocalcinosis could be an osteogenic cell‐driven process, similar to that of vascular calcifica‐ tion [64, 165–168]. Tubular epithelial cells have a well‐known ability to differentiate into cells with the mesenchymal phenotype (for instance, renal interstitial myofibroblasts may origi‐ nate from renal tubular cells undergoing epithelial‐mesenchymal transformation) [169]. This capacity for differentiation is not exclusive to renal cells, or epithelial cells. It is shared with Ito cells in the liver [170], and a subpopulation of smooth muscle cells (SMCs) in the intima of arteries—cell populations that are thought to be pericyte‐like. Remarkably, vascular peri‐ cytes have the ability to undergo osteoblastic differentiation and mineralization [171, 172], and seem to play a crucial part in ectopic vascular calcification.

The underlying mechanisms that lead to pathological calcification are complex and thought to involve active, strictly regulated processes that are common to bone formation [54, 173, 174]. Cells that may readily undergo osteogenic‐like transition include: vascular smooth muscle cells (VSMCs) [171, 175–193] in the media, myofibroblasts in the adventitia, pericytes in the microvessels [171, 172, 194], multipotent vascular mesenchymal progenitors, and valve inter‐ stitial cells [195, 196]. Vascular calcification was long thought to result from passive degenera‐ tion [197], but actually involves a complex, regulated process of biomineralization similar to osteogenesis, which mediates the deposition of bone matrix in the blood vessels [175–193].
