Zimmermann Laura-Marie A, Correns Annkatrin, Furlan Ariane G, Spanou Chara E S, Sengle Gerhard
Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; Center for Biochemistry, Faculty of Medicine, University Hospital of Cologne, Joseph-Stelzmann-Str. 52, 50931 Cologne, Germany.
Center for Biochemistry, Faculty of Medicine, University Hospital of Cologne, Joseph-Stelzmann-Str. 52, 50931 Cologne, Germany.
Cell Signal. 2021 Sep;85:110071. doi: 10.1016/j.cellsig.2021.110071. Epub 2021 Jul 2.
Bone morphogenetic proteins (BMPs) belong to the TGF-β superfamily of signaling ligands which comprise a family of pluripotent cytokines regulating a multitude of cellular events. Although BMPs were originally discovered as potent factors extractable from bone matrix that are capable to induce ectopic bone formation in soft tissues, their mode of action has been mostly studied as soluble ligands in absence of the physiologically relevant cellular microenvironment. This micro milieu is defined by supramolecular networks of extracellular matrix (ECM) proteins that specifically target BMP ligands, present them to their cellular receptors, and allow their controlled release. Here we focus on functional interactions and mechanisms that were described to control BMP bioavailability in a spatio-temporal manner within the respective tissue context. Structural disturbance of the ECM architecture due to mutations in ECM proteins leads to dysregulated BMP signaling as underlying cause for connective tissue disease pathways. We will provide an overview about current mechanistic concepts of how aberrant BMP signaling drives connective tissue destruction in inherited and chronic diseases.
骨形态发生蛋白（BMPs）属于转化生长因子-β（TGF-β）超家族的信号配体，该家族是一类多能细胞因子，可调节多种细胞活动。尽管BMPs最初被发现是能够从骨基质中提取的强效因子，能够在软组织中诱导异位骨形成，但其作用方式大多是在缺乏生理相关细胞微环境的情况下作为可溶性配体进行研究的。这种微环境由细胞外基质（ECM）蛋白的超分子网络定义，这些网络特异性靶向BMP配体，将它们呈现给细胞受体，并允许其可控释放。在这里，我们关注在各自组织背景下以时空方式控制BMP生物利用度的功能相互作用和机制。由于ECM蛋白突变导致的ECM结构紊乱会导致BMP信号失调，这是结缔组织疾病途径的潜在原因。我们将概述当前关于异常BMP信号如何在遗传性和慢性疾病中驱动结缔组织破坏的机制概念。
