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.
Highlights
Inflammation is an immune defense against pathogens or danger signals
We investigated whether CD4+ T cells express RANKL upon differentiation into Th17 cells
We demonstrated that conditioned medium from T-Mesenchymal stem cells (MSCs) (T-CM) can regulate Th17 cellinduced osteoclastogenesis via OPG, a soluble protein that inhibits production of OCLs
Summary
Inflammation is an immune defense against pathogens or danger signals. Persistent inflammatory responses result in chronic inflammatory diseases that are often associated with bone destruction, even when the inflammatory site is not the bone, such as in psoriasis [1,2,3]. Bone remodeling is a highly regulated process involving complex interactions between bone-forming osteoblasts (OBL) and boneresorbing OCLs [5]. These interactions require cell-tocell contact, cytokine production, and coupling factor generation during bone resorption. OCL generation is supported by OBLs, which produce macrophage colonystimulating factor (M-CSF) and receptor activator of nuclear factor- β ligand (RANKL), the two essential signals for OCL differentiation from myeloid cells such as inflammatory monocytes, macrophages, and dendritic cells [6, 7]. OBLs negatively regulate OCL by producing osteoprotegerin (OPG), a protein that inhibits the development of OCL, acts as a decoy receptor by sequestering RANKL and inhibiting RANK signaling [8]
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