文章：

多发性骨髓瘤骨病的发病机制：从实验室到临床

Pathogenesis of bone disease in multiple myeloma: from bench to bedside

原文发布日期：2018-01-12

DOI: 10.1038/s41408-017-0037-4

类型: Review Article

开放获取: 是

英文摘要：

Osteolytic bone disease is the hallmark of multiple myeloma, which deteriorates the quality of life of myeloma patients, and it affects dramatically their morbidity and mortality. The basis of the pathogenesis of myeloma-related bone disease is the uncoupling of the bone-remodeling process. The interaction between myeloma cells and the bone microenvironment ultimately leads to the activation of osteoclasts and suppression of osteoblasts, resulting in bone loss. Several intracellular and intercellular signaling cascades, including RANK/RANKL/OPG, Notch, Wnt, and numerous chemokines and interleukins are implicated in this complex process. During the last years, osteocytes have emerged as key regulators of bone loss in myeloma through direct interactions with the myeloma cells. The myeloma-induced crosstalk among the molecular pathways establishes a positive feedback that sustains myeloma cell survival and continuous bone destruction, even when a plateau phase of the disease has been achieved. Targeted therapies, based on the better knowledge of the biology, constitute a promising approach in the management of myeloma-related bone disease and several novel agents are currently under investigation. Herein, we provide an insight into the underlying pathogenesis of bone disease and discuss possible directions for future studies.

摘要翻译： 

溶骨性骨病是多发性骨髓瘤的典型特征，它不仅恶化骨髓瘤患者的生活质量，更显著影响其发病率和死亡率。骨髓瘤相关骨病的发病机制基础在于骨重塑过程的解偶联。骨髓瘤细胞与骨微环境的相互作用最终导致破骨细胞活化及成骨细胞抑制，从而引发骨质流失。这一复杂过程涉及多种细胞内与细胞间信号通路，包括RANK/RANKL/OPG、Notch、Wnt信号通路以及众多趋化因子和白介素。近年来，骨细胞通过直接与骨髓瘤细胞相互作用，已成为骨髓瘤骨质丢失的关键调节因子。骨髓瘤诱导的分子通路间交互作用形成了正向反馈循环，即使在疾病进入平台期后，仍能维持骨髓瘤细胞存活并持续破坏骨骼。基于对生物学机制的深入理解，靶向治疗已成为处理骨髓瘤相关骨病的有效策略，目前有多种新型药物正处于研究阶段。本文深入探讨骨病的潜在发病机制，并对未来研究方向提出展望。

原文链接：

Pathogenesis of bone disease in multiple myeloma: from bench to bedside