Chen Yue, Wang Qiang, Li Mengyue, Fang Yixuan, Bi Xiuting, Wu Jiameng, Han Qi, Zhu Hongfan, Shen Zhien, Wang Xiaoying
School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No.44-1 Wenhua Road West, Jinan, 250012, Shandong, China.
Jinan Key Medical and Health Laboratory of Oral Diseases and Tissue Regeneration, Shandong Provincial Key Medical and Health Laboratory of Oral Diseases and Tissue Regeneration, Jinan Stomatological Hospital, Jinan, 250001, Shandong Province, China.
J Mol Histol. 2025 Mar 17;56(2):108. doi: 10.1007/s10735-025-10385-8.
Nel-like molecule-1 (Nell-1), as a novel osteo-inductive molecule with great potential for clinical applications, has various functions including promoting chondrogenesis, suppressing osteoclastic activity, promoting osteogenesis, suppressing inflammation and promoting vascularization. Its anti-inflammatory potential has been widely studied. However, its anti-inflammatory potential in macrophage and possible underlying molecular mechanisms are poorly understood. Therefore, the present study aims to evaluate the anti-inflammatory potential and the regulation to macrophage polarization of Nell-1 in human myeloid cell line (THP-1) derived macrophages. M1-related markers and M2-related markers were studied in THP-1 derived macrophages. The suppressive potential of Nell-1 on lipopolysaccharide (LPS)-induced translocation of nuclear factor-kappa B (NF-κB) in THP-1 macrophage was studied. Results showed that Nell-1 significantly reduced M1 macrophage-related surface marker cluster of differentiation 86 (CD86) and inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) and reversed the LPS-induced M1 polarization of macrophages by upregulating the M2-specific markers of vascular endothelial growth factor (VEGF), arginase-1(Arg-1), and cluster of differentiation 206 (CD206) in vitro. In addition, the possible mechanism of the anti-inflammatory effects of Nell-1 is via regulating NF-κB pathway. Hence, Nell-1 is a potential suppressor of inflammation and is involved in the regulation of macrophage polarization. Nell-1 may be a potential candidate for treating inflammatory diseases and promoting tissue regeneration.
Nell样分子-1（Nell-1）作为一种具有巨大临床应用潜力的新型骨诱导分子，具有多种功能，包括促进软骨生成、抑制破骨细胞活性、促进成骨、抑制炎症和促进血管生成。其抗炎潜力已得到广泛研究。然而，其在巨噬细胞中的抗炎潜力及潜在分子机制尚不清楚。因此，本研究旨在评估Nell-1在人髓系细胞系（THP-1）来源的巨噬细胞中的抗炎潜力及其对巨噬细胞极化的调节作用。研究了THP-1来源巨噬细胞中与M1相关的标志物和与M2相关的标志物。研究了Nell-1对脂多糖（LPS）诱导的THP-1巨噬细胞核因子κB（NF-κB）转位的抑制潜力。结果表明，Nell-1显著降低了M1巨噬细胞相关表面标志物分化簇86（CD86）以及炎性细胞因子肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-1β（IL-1β），并通过上调血管内皮生长因子（VEGF）、精氨酸酶-1（Arg-1）和分化簇206（CD206）的M2特异性标志物在体外逆转了LPS诱导的巨噬细胞M1极化。此外，Nell-1抗炎作用的可能机制是通过调节NF-κB通路。因此，Nell-1是一种潜在的炎症抑制剂，参与巨噬细胞极化的调节。Nell-1可能是治疗炎症性疾病和促进组织再生的潜在候选物。
