Back to Search
Start Over
The inhibitory effects of a RANKL-binding peptide on articular and periarticular bone loss in a murine model of collagen-induced arthritis: a bone histomorphometric study.
- Source :
-
Arthritis research & therapy [Arthritis Res Ther] 2015 Sep 12; Vol. 17, pp. 251. Date of Electronic Publication: 2015 Sep 12. - Publication Year :
- 2015
-
Abstract
- Introduction: We designed OP3-4 (YCEIEFCYLIR), a cyclic peptide, to mimic the soluble osteoprotegerin (OPG), and was proven to bind to RANKL (receptor activator of NF-κB ligand), thereby inhibiting osteoclastogenesis. We recently found that another RANKL binding peptide, W9, could accelerate bone formation by affecting RANKL signaling in osteoblasts. We herein demonstrate the effects of OP3-4 on bone formation and bone loss in a murine model of rheumatoid arthritis.<br />Methods: Twenty-four seven-week-old male DBA/1J mice were used to generate a murine model of collagen-induced arthritis (CIA). Then, vehicle or OP3-4 (9 mg/kg/day or 18 mg/kg/day) was subcutaneously infused using infusion pumps for three weeks beginning seven days after the second immunization. The arthritis score was assessed, and the mice were sacrificed on day 49. Thereafter, radiographic, histological and biochemical analyses were performed.<br />Results: The OP3-4 treatment did not significantly inhibit the CIA-induced arthritis, but limited bone loss. Micro-CT images and quantitative measurements of the bone mineral density revealed that 18 mg/kg/day OP3-4 prevented the CIA-induced bone loss at both articular and periarticular sites of tibiae. As expected, OP3-4 significantly reduced the CIA-induced serum CTX levels, a marker of bone resorption. Interestingly, the bone histomorphometric analyses using undecalcified sections showed that OP3-4 prevented the CIA-induced reduction of bone formation-related parameters at the periarticular sites.<br />Conclusion: The peptide that mimicked OPG prevented inflammatory bone loss by inhibiting bone resorption and stimulating bone formation. It could therefore be a useful template for the development of small molecule drugs for inflammatory bone loss.
- Subjects :
- Amino Acid Sequence
Animals
Arthritis, Experimental metabolism
Arthritis, Experimental pathology
Arthritis, Rheumatoid drug therapy
Arthritis, Rheumatoid metabolism
Arthritis, Rheumatoid pathology
Bone Density drug effects
Bone Resorption metabolism
Cartilage, Articular metabolism
Cartilage, Articular pathology
Cell Differentiation drug effects
Cells, Cultured
Collagen Type I blood
Enzyme-Linked Immunosorbent Assay
Infusions, Subcutaneous
Male
Mice, Inbred DBA
Oligopeptides administration & dosage
Oligopeptides metabolism
Osteoblasts drug effects
Osteoblasts metabolism
Osteoclasts drug effects
Osteoclasts metabolism
Osteogenesis drug effects
Osteoprotegerin administration & dosage
Osteoprotegerin metabolism
Osteoprotegerin pharmacology
Peptides blood
Protein Binding
Tibia drug effects
Tibia metabolism
Tibia pathology
X-Ray Microtomography
Arthritis, Experimental drug therapy
Bone Resorption prevention & control
Cartilage, Articular drug effects
Oligopeptides pharmacology
RANK Ligand metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1478-6362
- Volume :
- 17
- Database :
- MEDLINE
- Journal :
- Arthritis research & therapy
- Publication Type :
- Academic Journal
- Accession number :
- 26373710
- Full Text :
- https://doi.org/10.1186/s13075-015-0753-8