COMP-Ang1 prevents periodontitic damages and enhances mandible bone growth in an experimental animal model

Abstract COMP-Ang1, a chimera of angiopoietin-1 (Ang1) and a short coiled-coil domain of cartilage oligomeric matrix protein (COMP), is under consideration as a therapeutic agent enhancing tissue regeneration with increased angiogenesis. However, the effect of COMP-Ang1 on periodontitic tissue damag...

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Bibliographic Details
Published in:Bone (New York, N.Y.) N.Y.), 2016-11, Vol.92, p.168-179
Main Authors: Bhattarai, Govinda, Kook, Sung-Ho, Kim, Jae-Hwan, Poudel, Sher Bahadur, Lim, Shin-Saeng, Seo, Young-Kwon, Lee, Jeong-Chae
Format: Article
Language:English
Subjects:
Animals
Bone Development - drug effects
Bone Development - physiology
Bone regeneration
COMP-Ang1
Dose-Response Relationship, Drug
Humans
Male
Mandible - diagnostic imaging
Mandible - drug effects
Mandible - growth & development
Mandible bone defect
Mice
Models, Animal
Orthopedics
Osteoclastogenesis
Periodontitis
Periodontitis - diagnostic imaging
Periodontitis - drug therapy
Rats
Rats, Sprague-Dawley
RAW 264.7 Cells
Recombinant Fusion Proteins - pharmacology
Recombinant Fusion Proteins - therapeutic use
Recombinant Proteins - pharmacology
Recombinant Proteins - therapeutic use
Signal transduction pathways
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Summary:Abstract COMP-Ang1, a chimera of angiopoietin-1 (Ang1) and a short coiled-coil domain of cartilage oligomeric matrix protein (COMP), is under consideration as a therapeutic agent enhancing tissue regeneration with increased angiogenesis. However, the effect of COMP-Ang1 on periodontitic tissue damages and the related mechanisms are not yet investigated. We initially explored whether a local delivery of COMP-Ang1 protects lipopolysaccharide (LPS)/ligature-induced periodontal destruction in rats. As the results, μCT and histological analyses revealed that COMP-Ang1 inhibits LPS-mediated degradation of periodontium. COMP-Ang1 also suppressed osteoclast number and the expression of osteoclast-specific and inflammation-related molecules in the inflamed region of periodontitis rats. Implanting a COMP-Ang1-impregnated scaffold into critical-sized mandible bone defects enhanced the amount of bone in the defects with increased expression of bone-specific markers. The addition of COMP-Ang1 prevented significantly osteoclast differentiation and activation in LPS-stimulated RAW264.7 macrophages and inhibited the phosphorylation of c-Jun., mitogen-activated protein kinases, and cAMP response element-binding protein in the cells. On contrary, COMP-Ang1 increased the level of phosphatidylinositol 3-kinase (PI3K) in LPS-exposed macrophages and a pharmacological PI3K inhibitor diminished the anti-osteoclastogenic effect of COMP-Ang1. Similarly, COMP-Ang1 blocked the expression of inflammation-related molecules in LPS-stimulated human periodontal ligament fibroblasts (hPLFs). Further, the COMP-Ang1 enhanced differentiation of hPLFs into osteoblasts by stimulating the expression of bone-specific markers, Tie2, and activator protein-1 subfamily. Collectively, our findings may support the therapeutic potentials of COMP-Ang1 in preventing inflammatory periodontal damages and in stimulating new bone growth.
ISSN:8756-3282
1873-2763
DOI:10.1016/j.bone.2016.09.002