Inorganic phosphate as a signaling molecule in osteoblast differentiation

Abstract

The spatial and temporal coordination of the many events required for osteogenic cells to create a mineralized matrix are only partially understood. The complexity of this process, and the nature of the final product, demand that these cells have mechanisms to carefully monitor events in the extracellular environment and have the ability to respond through cellular and molecular changes. The generation of inorganic phosphate during the process of differentiation may be one such signal. In addition to the requirement of inorganic phosphate as a component of hydroxyapatite mineral, Ca(10)(PO(4))(6)(OH)(2), a number of studies have also suggested it is required in the events preceding mineralization. However, contrasting results, physiological relevance, and the lack of a clear mechanism(s) have created some debate as to the significance of elevated phosphate in the differentiation process. More recently, a number of studies have begun to shed light on possible cellular and molecular consequences of elevated intracellular inorganic phosphate. These results suggest a model in which the generation of inorganic phosphate during osteoblast differentiation may in and of itself represent a signal capable of facilitating the temporal coordination of expression and regulation of multiple factors necessary for mineralization. The regulation of protein function and gene expression by elevated inorganic phosphate during osteoblast differentiation may represent a mechanism by which mineralizing cells monitor and respond to the changing extracellular environment.

EB1 Levels Are Elevated in Ascorbic Acid (AA)-stimulated Osteoblasts and Mediate Cell-Cell Adhesion-induced Osteoblast Differentiation

“…2). These results are in agreement with the notion that mineralization is a carefully orchestrated process, strongly influenced by increasing inorganic phosphate availability with ALP activity (48 delivery of matrix vesicles, rich in calcium, phosphate, and phosphoproteins, could also be at a disadvantage in cells with reduced EB1 levels (49). Thus, EB1 is also necessary for late stage osteoblast-mediated matrix mineralization.…”

Non-destructive characterisation of mesenchymal stem cell differentiation using LC-MS-based metabolite footprinting

“…34 The ALP changes and associated mineral deposits accumulation during osteogenic treatment containing ascorbic acid and beta glycerophosphate confirmed MSC differentiation during the 15-day time course. 35,36 Multivariate analysis of LC-MS profiling data…”

Effects of arachidonic acid and docosahexaenoic acid on differentiation and mineralization of MC3T3‐E1 osteoblast‐like cells

“…ALP hydrolyzes organophosphates thereby releasing inorganic phosphate, which appears to be the actual initiator of mineralization. 46 As osteoblasts continue to differentiate and enter the mineralization stage, levels of proteins associated with maturation such as ALP decline, while expression of osteocalcin and formation of hydroxyapatite become evident. 19 In our experiments, exposing MC3T3-E1 osteoblasts to physiological concentrations of AA for 48 h did not affect ALP activity.…”