Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.
Mineralization is an essential requirement for normal skeletal development, but under certain pathological conditions organs like articular cartilage and cardiovascular tissue are prone to unwanted mineralization. Recent findings suggest that the mechanisms regulating skeletal mineralization may be similar to those regulating pathological mineralization. In general, three forms of cell-mediated mineralization are recognized in an organism: intramembranous ossification, endochondral ossification and pathological mineralization. This review summarizes recent work that tried to elucidate how cell-mediated mineralization is initiated and regulated. To explain mineralization, several theories have been proposed. One theory proposes that mineralization is initiated within matrix vesicles (MVs). A second, not mutually exclusive, theory proposes that phosphate induces apoptosis, and that apoptotic bodies nucleate crystals composed of calcium and phosphate. A third theory suggests that mineralization is mediated by certain non-collagenous proteins, which associate with the extracellular matrix. Regardless of the way mineralization is initiated, the organism also actively inhibits mineralization by specific proteins and removal of an inhibitor may also induce mineralization. Although many studies greatly contributed to a better understanding of the mechanisms regulating cell-mediated mineralization, many questions remain about the mechanisms that trigger cell-mediated mineralization and how this process is regulated. Further investigation is necessary to develop in the future novel therapeutic strategies to prevent pathological mineralization.