成骨细胞代谢重编程与早期肾性骨病发生发展的研究进展

doi:10.12114/j.issn.1007-9572.2023.0799

摘要/Abstract

摘要： 慢性肾脏病矿物质和骨骼疾病（CKD-MBD）对患者的生活质量、住院率和骨折风险有直接影响。近年来成骨细胞及骨细胞成为CKD-MBD病理生理学研究的中心，成骨细胞通过合成成纤维细胞生长因子23（FGF-23）、硬化素等，与其他器官相互作用，使骨骼成为内分泌器官。因此，成骨细胞分化失调是慢性肾脏病发病过程中重要的早期事件。本文系统讨论了成骨细胞的代谢途径及早期CKD-MBD病理状态下成骨细胞代谢重编程改变的相关机制，表明Wnt家族分泌蛋白/β-连环蛋白（Wnt/β-catenin）、FGF-23、尿毒症毒素、代谢性酸中毒等信号通路及代谢物异常可改变成骨细胞代谢活性，引起成骨谱系成熟障碍，进而影响骨重塑，对于解释肾性骨病病理改变及临床治疗方案提供新思路。

关键词: 慢性肾疾病-矿物质和骨代谢异常, 肾性骨病, 细胞重新编程, 成纤维细胞生长因子23

Abstract:

Chronic kidney disease-mineral and bone disorder (CKD-MBD) has a direct impact on patients' quality of life, hospitalization rates and fracture risk. In recent years, osteoblasts and osteoclasts have become central to the pathophysiology of CKD-MBD. Osteoblasts interact with other organs by synthesizing fibroblast growth factor-23 (FGF-23) and sclerostin (SOST), making the skeleton an endocrine organ. Therefore, dysregulation of osteoblast differentiation is an important early event in the pathogenesis of CKD. In this paper, we systematically discuss the metabolic pathways of osteoblasts and the mechanisms related to the altered metabolic reprogramming of osteoblasts in the early CKD-MBD pathology. This paper shows that abnormalities in signaling pathways and metabolites such as Wnt/β-catenin, FGF-23, uremic toxins, metabolic acidosis, can alter the metabolic activity of osteoblasts, causing impaired maturation of the osteogenic spectrum, which in turn affects bone remodeling, which will provide a new way of thinking for explaining the pathological changes in renal bone disease and developing clinical treatment options.

Key words: Chronic kidney disease-mineral and bone disorder, Renal bone disease, Cellular reprogramming, Fibroblast growth factor-23

王左钰,周阳,熊明霞,等. 成骨细胞代谢重编程与早期肾性骨病发生发展的研究进展[J]. 中国全科医学, 2024, 27(15): 1904-1910. DOI: 10.12114/j.issn.1007-9572.2023.0799.
WANG Zuoyu,ZHOU Yang,XIONG Mingxia, et al. Advances in Metabolic Reprogramming of Osteoblasts with the Development of Early Renal Bone Disease[J]. Chinese General Practice, 2024, 27(15): 1904-1910. DOI: 10.12114/j.issn.1007-9572.2023.0799.

图/表 1

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项目	骨祖细胞	前体成骨细胞	成骨细胞	骨细胞
成骨细胞标志物
碱性磷酸酶	+	+	+	-
磷酸盐调节内肽酶	-	-	+	+
骨钙素	-	-	+	-
骨粘连蛋白	-	-	+	-
骨桥蛋白	-/+	-/+	+	+
骨唾液酸蛋白	-	+	+	+
Ⅰ型胶原蛋白	+	+	+	-
转录因子
RUNX2	-/+	+	+	+
OSTERIX	-/+	+	+	？
CREB	+	+	-	-
SATB2	-	-/+	+	+
ARF4	-	+	+	+
FIAT	？	+	-/+	-

项目	骨祖细胞	前体成骨细胞	成骨细胞	骨细胞
成骨细胞标志物
碱性磷酸酶	+	+	+	-
磷酸盐调节内肽酶	-	-	+	+
骨钙素	-	-	+	-
骨粘连蛋白	-	-	+	-
骨桥蛋白	-/+	-/+	+	+
骨唾液酸蛋白	-	+	+	+
Ⅰ型胶原蛋白	+	+	+	-
转录因子
RUNX2	-/+	+	+	+
OSTERIX	-/+	+	+	？
CREB	+	+	-	-
SATB2	-	-/+	+	+
ARF4	-	+	+	+
FIAT	？	+	-/+	-