Osteostatin Inhibits Collagen-Induced Arthritis by Regulation of Immune Activation, Pro-Inflammatory Cytokines, and Osteoclastogenesis

International Journal of Molecular Sciences
Josep Nácher-JuanMaría Luisa Ferrándiz

Abstract

In chronic inflammatory joint diseases, such as rheumatoid arthritis, there is an important bone loss. Parathyroid hormone-related protein (PTHrP) and related peptides have shown osteoinductive properties in bone regeneration models, but there are no data on inflammatory joint destruction. We have investigated whether the PTHrP (107-111) C-terminal peptide (osteostatin) could control the development of collagen-induced arthritis in mice. Administration of osteostatin (80 or 120 μg/kg s.c.) after the onset of disease decreased the severity of arthritis as well as cartilage and bone degradation. This peptide reduced serum IgG2a levels as well as T cell activation, with the downregulation of RORγt+CD4+ T cells and upregulation of FoxP3+CD8+ T cells in lymph nodes. The levels of key cytokines, such as interleukin(IL)-1β, IL-2, IL-6, IL-17, and tumor necrosis factor-α in mice paws were decreased by osteostatin treatment, whereas IL-10 was enhanced. Bone protection was related to reductions in receptor activator of nuclear factor-κB ligand, Dickkopf-related protein 1, and joint osteoclast area. Osteostatin improves arthritis and controls bone loss by inhibiting immune activation, pro-inflammatory cytokines, and osteoclastogenesis. Ou...Continue Reading

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Citations

Apr 10, 2020·International Journal of Molecular Sciences·Cristina Martínez-Villaluenga, Blanca Hernández-Ledesma
Jun 8, 2021·Advanced Science·Patricia Mora-RaimundoMaría Vallet-Regí
Jul 20, 2021·Frontiers in Immunology·Arnold E PostlethwaiteAndrzej T Slominski

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BETA
ELISA
chips
Assay
flow cytometry
X-ray

Software Mentioned

ARRIVE
GraphPad PRISM
FlowJo
GraphPad
FACS DIVA

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