Chen Qian, Wu ZuPing, Xie Liang
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Research Unit of Oral Carcinogenesis and Management, Chinese Academy of Medical Sciences, West China Hospital of Stomatology, Sichuan University, Chengdu, P. R. China.
The Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, P. R. China.
Ann N Y Acad Sci. 2022 Dec;1518(1):58-68. doi: 10.1111/nyas.14905. Epub 2022 Sep 30.
Intercellular communication or crosstalk between immune and skeletal cells is considered a crucial element in bone homeostasis modulation. Progranulin (PGRN) is an autocrine growth factor that is structured as beads-on-a-string and participates in multiple pathophysiological processes, including atherosclerosis, arthritis, neurodegenerative pathologies, cancer, and wound repair. PGRN functions as a competitor that binds to tumor necrosis factor receptor 1 (TNFR1), thereby blocking the TNF-α pathway. PGRN is regarded as an agonist of chondrogenesis and osteogenesis, delaying the progression of inflammation through the TNFR2 pathway. The exploitation of PGRN may bring benefits for inflammatory bone diseases and the stabilization of bone homeostasis. The PGRN-modified analog Atsttrin possesses three TNFR-binding fragments and thereby exerts superior therapeutic effects on multiple preclinical animal models compared to PGRN. In this review, we highlight the emerging roles of PGRN in bone formation, as well as in physiological and TNF-α-mediated inflammatory conditions revealed in recent discoveries. We address potential therapies for the treatment of inflammatory bone conditions, such as periodontitis, by the use of PGRN and its derivative Atsttrin.
免疫细胞与骨骼细胞之间的细胞间通讯或串扰被认为是调节骨稳态的关键因素。前颗粒蛋白（PGRN）是一种自分泌生长因子，其结构为串珠状，参与多种病理生理过程，包括动脉粥样硬化、关节炎、神经退行性疾病、癌症和伤口修复。PGRN作为一种竞争者，与肿瘤坏死因子受体1（TNFR1）结合，从而阻断TNF-α途径。PGRN被视为软骨生成和成骨的激动剂，通过TNFR2途径延缓炎症进展。对PGRN的开发可能会给炎症性骨疾病和骨稳态的稳定带来益处。PGRN修饰的类似物Atsttrin具有三个TNFR结合片段，因此与PGRN相比，在多种临床前动物模型上具有更好的治疗效果。在这篇综述中，我们重点介绍了PGRN在骨形成中的新作用，以及在最近发现中揭示的生理和TNF-α介导的炎症状态中的作用。我们探讨了使用PGRN及其衍生物Atsttrin治疗炎症性骨疾病（如牙周炎）的潜在疗法。
