[Updates on rickets and osteomalacia: mechanism and regulation of bone mineralization].
Bone is mineralized when hydroxyapatite crystals derived from calcium ions and inorganic phosphate (Pi) grow along collagen fibrils in the extracellular matrix. Mineralization is initiated by nucleation of those crystals. Mature osteoblasts secrete matrix vesicles into osteoid, which contain growing hydroxyapatite crystal seeds. After rupture of the lipid bilayer of those vesicles, crystals continue to grow as a mineralized nodule and adhere to collagen fibrils. It remains controversial whether nucleation occurs mainly in matrix vesicles or also extra-vesicularly around collagen fibrils. Mineralization is inhibited by pyrophosphate (PPi) and by SIBLING family proteins, which carry an acidic serine- and aspartate-rich motif (ASARM) and include osteopontin, dentin matrix protein 1 and MEPE. Intracellular and extracellular activity of these factors is regulated by the PPi-generating ectonucleotide pyrophosphatase/phosphodiesterase (ENPP1) , the PPi-transporter progressive ankylosis (ANK) protein, the PPi-degrading/Pi-generating ectoenzyme alkaline phosphatase (ALPL, TNAP) , and PHEX endopeptidase. Gain- or loss-of-function mutations in genes encoding these proteins are associated with mineralization disorders such as ectopic calcification and other pathologies.
Laboratory of Cell and Tissue Biology, School of Medicine, Keio University, Japan.
Koichi
K
Matsuo
D000818:Animals; D002113:Calcification, Physiologic / Q000502:physiology*; D011756:Diphosphates / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D053402:PHEX Phosphate Regulating Neutral Endopeptidase / Q000378:metabolism; D012279:Rickets / Q000378:metabolism*; D015398:Signal Transduction
D011756:Diphosphates; D016326:Extracellular Matrix Proteins; D053402:PHEX Phosphate Regulating Neutral Endopeptidase