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

• Main Authors: Josep Nácher-Juan, María Carmen Terencio, María José Alcaraz, María Luisa Ferrándiz
• Format: Article
• Language: English
• Published: MDPI AG 2019-08-01
• Series: International Journal of Molecular Sciences
• Subjects: osteostatin; arthritis; inflammation; immune response; cartilage destruction; bone erosion
• Online Access: https://www.mdpi.com/1422-0067/20/16/3845

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. Our results support the interest of osteostatin for the treatment of inflammatory joint conditions.