Kim Soo-In, Rha Min-Seok, Kim Jinsun, Ahn Sang Hyeon, Ryu Ji-Hwan, Cho Hyung-Ju, Kim Chang-Hoon
The Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
Department of Biomedical Sciences, Yonsei University College of Medicine, Seoul, Republic of Korea.
Front Immunol. 2025 Jun 18;16:1596746. doi: 10.3389/fimmu.2025.1596746. eCollection 2025.
Eosinophilic chronic rhinosinusitis (ECRS) is a severe form of chronic rhinosinusitis characterized by type 2 inflammation, tissue remodeling, and bone thickening, known as osteitis. Periostin, a matricellular protein involved in extracellular matrix (ECM) regulation and T helper 2 (Th2)-mediated inflammation, is markedly elevated in patients with ECRS; however, its pathophysiological role remains unclear.
We investigated the role of periostin in inflammation and tissue remodeling in ECRS using samples from ECRS patients, human nasal epithelial cells and fibroblasts, as well as an ECRS mouse model including periostin knockout mice.
Periostin levels were elevated in ECRS tissues and modestly correlated with osteitis scores. Th2 cytokines increased periostin expression, particularly in nasal fibroblasts. Conditioned medium containing periostin promoted osteogenic differentiation , whereas neutralizing antibodies reduced the expression of osteogenic markers. In an ECRS mouse model, periostin deficiency led to reduced bone thickening and lower expression of osteogenic markers despite similar eosinophil infiltration. Furthermore, periostin-deficient mice exhibited greater epithelial collapse and reduced fibronectin levels, indicating compromised ECM integrity.
These findings demonstrate that periostin contributes to osteogenesis and maintenance of structural stability in the inflamed sinonasal mucosa. Periostin may be a potential therapeutic target for controlling chronic inflammation and tissue remodeling in ECRS.
嗜酸性粒细胞性慢性鼻-鼻窦炎（ECRS）是慢性鼻-鼻窦炎的一种严重形式，其特征为2型炎症、组织重塑和骨质增厚，即骨炎。骨膜蛋白是一种参与细胞外基质（ECM）调节和辅助性T细胞2（Th2）介导的炎症反应的基质细胞蛋白，在ECRS患者中显著升高；然而，其病理生理作用仍不清楚。
我们使用ECRS患者的样本、人鼻上皮细胞和成纤维细胞，以及包括骨膜蛋白基因敲除小鼠在内的ECRS小鼠模型，研究了骨膜蛋白在ECRS炎症和组织重塑中的作用。
ECRS组织中骨膜蛋白水平升高，且与骨炎评分呈中度相关。Th2细胞因子增加骨膜蛋白表达，尤其是在鼻成纤维细胞中。含有骨膜蛋白的条件培养基促进成骨分化，而中和抗体则降低成骨标志物的表达。在ECRS小鼠模型中，尽管嗜酸性粒细胞浸润相似，但骨膜蛋白缺乏导致骨质增厚减少和成骨标志物表达降低。此外，骨膜蛋白缺乏的小鼠表现出更大程度的上皮塌陷和纤连蛋白水平降低，表明ECM完整性受损。
这些发现表明，骨膜蛋白有助于炎症鼻窦黏膜的成骨和结构稳定性的维持。骨膜蛋白可能是控制ECRS慢性炎症和组织重塑的潜在治疗靶点。
