CSF1R as a Therapeutic Target in Bone Diseases: Obvious but Not so Simple.

IF 4.2 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Current Osteoporosis Reports Pub Date : 2022-12-01 DOI:10.1007/s11914-022-00757-4

David A Hume, Lena Batoon, Anuj Sehgal, Sahar Keshvari, Katharine M Irvine

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引用次数: 5

Abstract

Purpose of review: The purpose of the review is to summarize the expression and function of CSF1R and its ligands in bone homeostasis and constraints on therapeutic targeting of this axis.

Recent findings: Bone development and homeostasis depends upon interactions between mesenchymal cells and cells of the mononuclear phagocyte lineage (MPS), macrophages, and osteoclasts (OCL). The homeostatic interaction is mediated in part by the systemic and local production of growth factors, macrophage colony-stimulating factor (CSF1), and interleukin 34 (IL34) that interact with a receptor (CSF1R) expressed exclusively by MPS cells and their progenitors. Loss-of-function mutations in CSF1 or CSF1R lead to loss of OCL and macrophages and dysregulation of postnatal bone development. MPS cells continuously degrade CSF1R ligands via receptor-mediated endocytosis. As a consequence, any local or systemic increase or decrease in macrophage or OCL abundance is rapidly reversible. In principle, both CSF1R agonists and antagonists have potential in bone regenerative medicine but their evaluation in disease models and therapeutic application needs to carefully consider the intrinsic feedback control of MPS biology.

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CSF1R作为骨病的治疗靶点:显而易见但不那么简单。

综述目的:综述CSF1R及其配体在骨稳态中的表达和功能，以及对该轴治疗靶向性的限制。近期研究发现:骨的发育和体内平衡依赖于间充质细胞和单核吞噬细胞系(MPS)、巨噬细胞和破骨细胞(OCL)之间的相互作用。这种稳态相互作用部分是由生长因子、巨噬细胞集落刺激因子(CSF1)和白细胞介素34 (IL34)的系统和局部产生介导的，这些因子与MPS细胞及其祖细胞特异性表达的受体(CSF1R)相互作用。CSF1或CSF1R的功能缺失突变导致OCL和巨噬细胞的缺失以及出生后骨发育的失调。MPS细胞通过受体介导的内吞作用持续降解CSF1R配体。因此，任何局部或全身巨噬细胞或OCL丰度的增加或减少都是迅速可逆的。原则上，CSF1R激动剂和拮抗剂在骨再生医学中都有潜力，但它们在疾病模型和治疗应用中的评估需要仔细考虑MPS生物学的内在反馈控制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current Osteoporosis Reports Medicine-Endocrinology, Diabetes and Metabolism

CiteScore

8.80

自引率

2.30%

发文量

期刊介绍： This journal intends to provide clear, insightful, balanced contributions by international experts that review the most important, recently published clinical findings related to the diagnosis, treatment, management, and prevention of osteoporosis. We accomplish this aim by appointing international authorities to serve as Section Editors in key subject areas, such as current and future therapeutics, epidemiology and pathophysiology, and evaluation and management. Section Editors, in turn, select topics for which leading experts contribute comprehensive review articles that emphasize new developments and recently published papers of major importance, highlighted by annotated reference lists. An international Editorial Board reviews the annual table of contents, suggests articles of special interest to their country/region, and ensures that topics are current and include emerging research. Commentaries from well-known figures in the field are also provided.