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.

中文翻译：

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颗粒蛋白前体对于骨稳态和免疫学至关重要

免疫细胞和骨骼细胞之间的细胞间通讯或串扰被认为是骨稳态调节的关键因素。颗粒体蛋白原 (PGRN) 是一种自分泌生长因子，其结构类似于串珠，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 作为竞争者与肿瘤坏死因子受体 1 (TNFR1) 结合，从而阻断 TNF-α 通路。PGRN 被认为是软骨形成和成骨的激动剂，通过 TNFR2 途径延缓炎症的进展。PGRN 的开发可能为炎症性骨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，它对多种临床前动物模型具有更好的治疗效果。在这篇综述中，我们强调了 PGRN 在骨形成以及最近发现的生理和 TNF-α 介导的炎症状况中的新作用。我们通过使用 PGRN 及其衍生物 Atsttrin 解决了治疗炎症性骨病（如牙周炎）的潜在疗法。