The inorganic phosphate/inorganic pyrophosphate axis in the mineralization of cartilage and bone

PURPOSE OF REVIEW: A cogent description of the intersection of inorganic phosphate and inorganic pyrophosphate utilization in bone and cartilage is emerging from areas of research as diverse as human genetics and inorganic chemistry. The review discusses recent developments in our understanding of the roles of these important constituents in cell and animal model systems, and in human disease. RECENT FINDINGS: At center stage in the process of biomineralization are inorganic phosphate, required for physiological mineralization of hard tissues, and inorganic pyrophosphate, a potent inhibitor of mineralization. Studies in cell model systems suggest that inorganic phosphate and inorganic pyrophosphate elaboration can trigger novel pathways of signal transduction, and that the induction of certain signaling pathways may affect the uptake of inorganic phosphate and inorganic pyrophosphate by mineralization-competent cells. Animal models of physiological and pathological mineralization describe the roles that phosphatases, phosphodiesterases, inorganic pyrophosphate transporters and osteopontin play in the inorganic phosphate/inorganic pyrophosphate mineralization axis. Studies from human disease suggest that other proteins and hormones may be important in the regulation of phosphate homeostasis and skeletal mineralization. SUMMARY: A closely regulated ratio of phosphate to pyrophosphate is required for the appropriate mineralization of skeletal tissues. Furthermore, maintenance of homeostasis in the inorganic phosphate/inorganic pyrophosphate ratio must be maintained in soft tissues to prevent pathological mineralization. Human disease and animal models are clarifying the roles of phosphate and pyrophosphate in both physiological and pathological biomineralization.