At the Crux of Joint Crosstalk: TGFβ Signaling in the Synovial Joint.

IF 5.7 2区医学 Q1 RHEUMATOLOGY Current Rheumatology Reports Pub Date : 2022-06-01 Epub Date: 2022-05-02 DOI:10.1007/s11926-022-01074-6

Karsyn N Bailey, Tamara Alliston

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Abstract

Purpose of review: The effect of the transforming growth factor beta (TGFβ) signaling pathway on joint homeostasis is tissue-specific, non-linear, and context-dependent, representing a unique complexity in targeting TGFβ signaling in joint disease. Here we discuss the variety of mechanisms that TGFβ signaling employs in the synovial joint to maintain healthy joint crosstalk and the ways in which aberrant TGFβ signaling can result in joint degeneration.

Recent findings: Osteoarthritis (OA) epitomizes a condition of disordered joint crosstalk in which multiple joint tissues degenerate leading to overall joint deterioration. Synovial joint tissues, such as subchondral bone, articular cartilage, and synovium, as well as mesenchymal stem cells, each demonstrate aberrant TGFβ signaling during joint disease, whether by excessive or suppressed signaling, imbalance of canonical and non-canonical signaling, a perturbed mechanical microenvironment, or a distorted response to TGFβ signaling during aging. The synovial joint relies upon a sophisticated alliance among each joint tissue to maintain joint homeostasis. The TGFβ signaling pathway is a key regulator of the health of individual joint tissues, and the subsequent interaction among these different joint tissues, also known as joint crosstalk. Dissecting the sophisticated function of TGFβ signaling in the synovial joint is key to therapeutically interrogating the pathway to optimize overall joint health.

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关节串联的关键：滑膜关节中的 TGFβ 信号传递

综述的目的：转化生长因子β（TGFβ）信号通路对关节稳态的影响具有组织特异性、非线性和上下文依赖性，是关节疾病中靶向 TGFβ 信号的独特复杂性。在此，我们将讨论TGFβ信号在滑膜关节中维持健康关节串联的各种机制，以及TGFβ信号异常导致关节退化的方式：骨关节炎（OA）是关节串联失调的缩影，在这种情况下，多个关节组织退化，导致整体关节退化。滑膜关节组织，如软骨下骨、关节软骨和滑膜，以及间充质干细胞，在关节疾病期间都会表现出异常的 TGFβ 信号传导，无论是信号传导过多或受抑制、规范信号传导与非规范信号传导失衡、机械微环境紊乱，还是老化过程中对 TGFβ 信号传导的扭曲反应。滑膜关节依靠各关节组织之间复杂的联盟来维持关节的平衡。TGFβ 信号通路是各个关节组织健康的关键调节器，也是这些不同关节组织之间后续相互作用的关键调节器，也称为关节串扰。剖析滑膜关节中 TGFβ 信号传导的复杂功能，是对该通路进行治疗研究以优化整体关节健康的关键。

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来源期刊

Current Rheumatology Reports RHEUMATOLOGY-

CiteScore

11.20

自引率

0.00%

发文量

期刊介绍： This journal aims to review the most important, recently published research in the field of rheumatology. By providing clear, insightful, balanced contributions by international experts, the journal intends to serve all those involved in the care and prevention of rheumatologic conditions. We accomplish this aim by appointing international authorities to serve as Section Editors in key subject areas such as the many forms of arthritis, osteoporosis and metabolic bone disease, and systemic lupus erythematosus. 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 occasionally provided.