Matsuo Koichi
Laboratory of Cell and Tissue Biology, School of Medicine, Keio University, Japan.
Clin Calcium. 2013 Oct;23(10):1463-7.
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.
当源自钙离子和无机磷酸盐（Pi）的羟基磷灰石晶体沿着细胞外基质中的胶原纤维生长时，骨发生矿化。矿化由这些晶体的成核作用启动。成熟的成骨细胞将基质小泡分泌到类骨质中，这些小泡含有正在生长的羟基磷灰石晶体种子。这些小泡的脂质双分子层破裂后，晶体继续生长形成矿化结节并附着在胶原纤维上。成核作用主要发生在基质小泡中还是也发生在胶原纤维周围的小泡外仍存在争议。矿化受到焦磷酸（PPi）和SIBLING家族蛋白的抑制，这些蛋白带有富含酸性丝氨酸和天冬氨酸的基序（ASARM），包括骨桥蛋白、牙本质基质蛋白1和MEPE。这些因子的细胞内和细胞外活性由产生PPi的胞外核苷酸焦磷酸酶/磷酸二酯酶（ENPP1）、PPi转运蛋白进行性骨化性肌炎（ANK）蛋白、降解PPi/产生Pi的胞外酶碱性磷酸酶（ALPL，TNAP）和PHEX内肽酶调节。编码这些蛋白的基因的功能获得或丧失突变与矿化障碍如异位钙化和其他病理状况相关。
