Michigami Toshimi
Department of Bone and Mineral Research, Research Institute, Osaka Women's and Children's Hospital, Osaka Prefectural Hospital Organization, Osaka, Japan.
Clin Pediatr Endocrinol. 2023;32(1):1-10. doi: 10.1297/cpe.2022-0053. Epub 2022 Sep 19.
Osteocytes are dendritic-shaped cells embedded in the bone matrix and are terminally differentiated from osteoblasts. Inaccessibility due to their location has hindered the understanding of the molecular functions of osteocytes. However, scientific advances in the past few decades have revealed that osteocytes play critical roles in bone and mineral metabolism through their paracrine and endocrine functions. Sclerostin produced by osteocytes regulates bone formation and resorption by inhibiting Wnt/β-catenin signaling in osteoblast-lineage cells. Receptor activator of nuclear factor κ B ligand (RANKL) derived from osteocytes is essential for osteoclastogenesis and osteoclast activation during postnatal life. Osteocytes also secrete fibroblast growth factor 23 (FGF23), an endocrine FGF that regulates phosphate metabolism mainly by increasing phosphate excretion and decreasing 1, 25-dihydroxyvitamin D production in the kidneys. The regulation of FGF23 production in osteocytes is complex and multifactorial, involving many local and systemic regulators. Antibodies against sclerostin, RANKL, and FGF23 have emerged as new strategies for the treatment of metabolic bone diseases. Improved undrstanding of the paracrine and endocrine functions of osteocytes will provide insight into future therapeutic options.
骨细胞是嵌入骨基质中的树突状细胞，由成骨细胞终末分化而来。因其位置难以接近，阻碍了对骨细胞分子功能的了解。然而，过去几十年的科学进展表明，骨细胞通过其旁分泌和内分泌功能在骨和矿物质代谢中发挥关键作用。骨细胞产生的硬化蛋白通过抑制成骨细胞系细胞中的Wnt/β-连环蛋白信号传导来调节骨形成和吸收。骨细胞衍生的核因子κB受体活化因子配体（RANKL）对于出生后破骨细胞生成和破骨细胞活化至关重要。骨细胞还分泌成纤维细胞生长因子23（FGF23），这是一种内分泌FGF，主要通过增加磷酸盐排泄和减少肾脏中1,25-二羟基维生素D的产生来调节磷酸盐代谢。骨细胞中FGF23产生的调节是复杂且多因素的，涉及许多局部和全身调节因子。针对硬化蛋白、RANKL和FGF23的抗体已成为治疗代谢性骨病的新策略。对骨细胞旁分泌和内分泌功能的进一步了解将为未来的治疗选择提供思路。
