Energy-Dependent Phosphate and Acid Transport for Bone Formation and Resorption

Abstract

Bone formation and resorption are mediated by an epithelial-like cell layer on bone. Formation or resorption requires active transport that depends on aerobic glycolysis, ATP, and acid transport. Metabolic activity of bone cells during matrix formation or removal is so high that the cells autolyze rapidly after cell death. Mineralization of bone matrix uses import of phosphate by sodium-phosphate cotransport, supported by the Na⁺/K⁺ ATPase. Glucose is the main energy source; ATP is exported to generate phosphate for hydroxyapatite in the bone matrix. Mechanism of export is not established, but phosphate is generated at least in part via phosphatase/pyrophosphatase activity including the tissue nonspecific alkaline phosphatase (TNAP) and ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2). Ca²⁺ is imported by paracellular transport. Protons, generated in producing hydroxyapatite, are exported by apical H⁺/Cl⁻ exchangers ClC3 and ClC5, and basolateral Na⁺/H⁺ exchange. In bone resorption, ATP-dependent acid transport, the reverse of acid transport in bone formation, is essential. This uses the vacuolar-type H⁺ATPase linked to Cl⁻ transport via a ClC family H⁺/Cl⁻ exchanger, ClC7, and a Cl⁻ channel. Other transporters contributing include carbonic anhydrase and chloride-bicarbonate exchange to replace H⁺ equivalents exported for bone resorption.

New and Noteworthy

This focused short review considers the relationship of oxidative phosphorylation to acid transport in bone formation and resorption, processes with very high metabolic activity for storage or removal of phosphate, calcium and acid equivalents.