Giusti Veronica, Scotlandi Katia
Laboratory of Experimental Oncology, IRCCS Istituto Ortopedico Rizzoli, 40136, Bologna, Italy.
J Cell Commun Signal. 2021 Dec;15(4):545-566. doi: 10.1007/s12079-021-00631-5. Epub 2021 Jul 6.
The acronym for the CCN family was recently revised to represent "cellular communication network". These six, small, cysteine-enriched and evolutionarily conserved proteins are secreted matricellular proteins, that convey and modulate intercellular communication by interacting with structural proteins, signalling factors and cell surface receptors. Their role in the development and physiology of musculoskeletal system, constituted by connective tissues where cells are interspersed in the cellular matrix, has been broadly studied. Previous research has highlighted a crucial balance of CCN proteins in mesenchymal stem cell commitment and a pivotal role for CCN1, CCN2 and their alter ego CCN3 in chondrogenesis and osteogenesis; CCN4 plays a minor role and the role of CCN5 and CCN6 is still unclear. CCN proteins also participate in osteoclastogenesis and myogenesis. In adult life, CCN proteins serve as mechanosensory proteins in the musculoskeletal system providing a steady response to environmental stimuli and participating in fracture healing. Substantial evidence also supports the involvement of CCN proteins in inflammatory pathologies, such as osteoarthritis and rheumatoid arthritis, as well as in cancers affecting the musculoskeletal system and bone metastasis. These matricellular proteins indeed show involvement in inflammation and cancer, thus representing intriguing therapeutic targets. This review discusses the current understanding of CCN proteins in the musculoskeletal system as well as the controversies and challenges associated with their multiple and complex roles, and it aims to link the dispersed knowledge in an effort to stimulate and guide readers to an area that the writers consider to have significant impact and relevant potentialities.
CCN家族的首字母缩写最近被修订为代表“细胞通讯网络”。这六种富含半胱氨酸且在进化上保守的小蛋白是分泌型基质细胞蛋白，它们通过与结构蛋白、信号因子和细胞表面受体相互作用来传递和调节细胞间通讯。它们在肌肉骨骼系统的发育和生理学中的作用已得到广泛研究，肌肉骨骼系统由结缔组织构成，细胞散布于细胞基质中。先前的研究强调了CCN蛋白在间充质干细胞定向分化中的关键平衡，以及CCN1、CCN2及其类似物CCN3在软骨形成和骨形成中的关键作用；CCN4起次要作用，而CCN5和CCN6的作用仍不清楚。CCN蛋白还参与破骨细胞生成和成肌过程。在成年期，CCN蛋白在肌肉骨骼系统中充当机械感应蛋白，对环境刺激提供稳定反应并参与骨折愈合。大量证据也支持CCN蛋白参与炎症性疾病，如骨关节炎和类风湿关节炎，以及影响肌肉骨骼系统和骨转移的癌症。这些基质细胞蛋白确实显示出与炎症和癌症有关，因此代表了引人关注的治疗靶点。本综述讨论了目前对CCN蛋白在肌肉骨骼系统中的理解，以及与其多重和复杂作用相关的争议和挑战，旨在将分散的知识联系起来，以激发和引导读者关注作者认为具有重大影响和相关潜力的领域。
