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Osteostatin Inhibits Collagen-Induced Arthritis by Regulation of Immune Activation, Pro-Inflammatory Cytokines, and Osteoclastogenesis
- Source :
- RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia, instname, International Journal of Molecular Sciences, International Journal of Molecular Sciences, Vol 20, Iss 16, p 3845 (2019), Volume 20, Issue 16
- Publication Year :
- 2019
- Publisher :
- MDPI AG, 2019.
-
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 &mu<br />g/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 ROR&gamma<br />t+CD4+ T cells and upregulation of FoxP3+CD8+ T cells in lymph nodes. The levels of key cytokines, such as interleukin(IL)-1&beta<br />IL-2, IL-6, IL-17, and tumor necrosis factor-&alpha<br />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-&kappa<br />B 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.
- Subjects :
- 0301 basic medicine
Male
Biopsy
T-Lymphocytes
Arthritis
Bone erosion
immune response
lcsh:Chemistry
Mice
0302 clinical medicine
Osteogenesis
lcsh:QH301-705.5
Spectroscopy
bone erosion
FOXP3
General Medicine
humanities
Computer Science Applications
medicine.anatomical_structure
arthritis
Disease Progression
Cytokines
Tumor necrosis factor alpha
Disease Susceptibility
medicine.symptom
Inflammation Mediators
hormones, hormone substitutes, and hormone antagonists
musculoskeletal diseases
T cell
cartilage destruction
Cartilage destruction
Inflammation
Catalysis
Article
Bone and Bones
Proinflammatory cytokine
Inorganic Chemistry
03 medical and health sciences
osteostatin
Osteoclast
medicine
Animals
Physical and Theoretical Chemistry
Immune response
Bone regeneration
Molecular Biology
Peroxidase
business.industry
Organic Chemistry
Parathyroid Hormone-Related Protein
Osteostatin
medicine.disease
Arthritis, Experimental
Peptide Fragments
Disease Models, Animal
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
inflammation
Immunoglobulin G
Cancer research
business
Biomarkers
030215 immunology
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia, instname, International Journal of Molecular Sciences, International Journal of Molecular Sciences, Vol 20, Iss 16, p 3845 (2019), Volume 20, Issue 16
- Accession number :
- edsair.doi.dedup.....39a8e636e417e2e53430036ac6dbc935
- Full Text :
- https://doi.org/10.3390/ijms20163845