Cell biology of calcified tissues: Experimental models of differentiation and mechanisms by which local and systemic factors exert their effects

Interpretation of the cell biology literature, as it relates to formation and mineralization of calcifying tissues, is complicated by the plethora of models available. Some culture models use heterogeneous populations of cells while others use relatively homogeneous populations. The issues are further confused by comparison of monolayer and three dimensional cultures. In addition, transformed and nontransformed cell lines are also used. As little clinical data about the age and sex of the original donor for many of these cell lines is lacking, it is impossible to know where in the cell lineage the cells were when they were isolated, yet this information can have a direct impact on the data obtained and their interpretation. Furthermore, many responses are attributed to the cell, while much of the effect observed may be targeted to the matrix. These issues are discussed and a potential mechanism explaining how cells can modulate events in the matrix nongenomically is presented.