Mesenchymal stem cells inhibit RANK-RANKL interactions between osteoclasts and Th17 cells via osteoprotegerin activity

// Kyung-Ah Cho 1 , Minhwa Park 1 , Yu-Hee Kim 1 , Kyung-Ha Ryu 2 and So-Youn Woo 1 1 Department of Microbiology, College of Medicine, Ewha Womans University, Seoul, Republic of Korea 2 Department of Pediatrics, College of Medicine, Ewha Womans University, Seoul, Republic of Korea Correspondence to: So-Youn Woo, email: // Keywords : mesenchymal stem cells, osteoprotegerin, Th17 cells, osteoclasts, psoriasis, Immunology and Microbiology Section, Immune response, Immunity Received : February 20, 2017 Accepted : September 05, 2017 Published : September 28, 2017 Abstract 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 via direct cell-to-cell interactions is less understood. In this study, we observed that Th17 cells directly promote osteoclast differentiation and maturation via expression of receptor activator of nuclear factor-κ β ligand (RANKL) in vitro . 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 via 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 ( via OPG production) for the treatment of pathophysiologic processes induced by osteoclasts under chronic inflammatory conditions such as psoriasis.