Cho Kyung-Ah, Park Minhwa, Kim Yu-Hee, Ryu Kyung-Ha, Woo So-Youn
Department of Microbiology, College of Medicine, Ewha Womans University, Seoul, Republic of Korea.
Department of Pediatrics, College of Medicine, Ewha Womans University, Seoul, Republic of Korea.
Oncotarget. 2017 Sep 28;8(48):83419-83431. doi: 10.18632/oncotarget.21379. eCollection 2017 Oct 13.
Th17 cells play a critical role in several autoimmune diseases, including psoriasis and psoriatic arthritis (PsA). Psoriasis is a chronic inflammatory skin disease associated with systemic inflammation and comorbidities, such as PsA. PsA develops in nearly 70% of patients with psoriasis, and osteoclasts associated bone erosion is a hallmark of the disease. Thus far, the effect of Th17 cells on osteoclastogenesis direct cell-to-cell interactions is less understood. In this study, we observed that Th17 cells directly promote osteoclast differentiation and maturation expression of receptor activator of nuclear factor-κ β ligand (RANKL) . We investigated the impact of conditioned medium obtained from human palatine tonsil-derived mesenchymal stem cells (T-CM) on the interactions between osteoclasts and Th17 cells. T-CM effectively blunted the RANK-RANKL interaction between the osteoclast precursor cell line RAW 264.7 and Th17 cells osteoprotegerin (OPG) activity. The frequency of tartrate-resistant acid phosphatase (TRAP)-positive cells in the bone marrow of an imiquimod (IMQ)-induced psoriasis mouse model was decreased following T-CM injection. Therefore, our data provide novel insight into the therapeutic potential of tonsil-derived mesenchymal stem cell-mediated therapy ( OPG production) for the treatment of pathophysiologic processes induced by osteoclasts under chronic inflammatory conditions such as psoriasis.
辅助性T细胞17(Th17细胞)在包括银屑病和银屑病关节炎(PsA)在内的多种自身免疫性疾病中起关键作用。银屑病是一种与全身炎症及合并症(如PsA)相关的慢性炎症性皮肤病。近70%的银屑病患者会发展为PsA,破骨细胞相关的骨侵蚀是该疾病的一个标志。到目前为止,Th17细胞对破骨细胞生成的直接细胞间相互作用的影响还了解较少。在本研究中,我们观察到Th17细胞通过核因子κB受体活化因子配体(RANKL)的表达直接促进破骨细胞的分化和成熟。我们研究了人腭扁桃体来源的间充质干细胞条件培养基(T-CM)对破骨细胞与Th17细胞之间相互作用的影响。T-CM通过骨保护素(OPG)活性有效减弱了破骨细胞前体细胞系RAW 264.7与Th17细胞之间的RANK-RANKL相互作用。在咪喹莫特(IMQ)诱导的银屑病小鼠模型骨髓中,注射T-CM后抗酒石酸酸性磷酸酶(TRAP)阳性细胞的频率降低。因此,我们的数据为扁桃体来源的间充质干细胞介导的治疗(产生OPG)在治疗银屑病等慢性炎症条件下由破骨细胞诱导的病理生理过程的治疗潜力提供了新的见解。