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.
Original language | English |
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Pages (from-to) | 168-179 |
Number of pages | 12 |
Journal | Bone |
Volume | 92 |
DOIs | |
State | Published - 1 Nov 2016 |
Keywords
- Bone regeneration
- COMP-Ang1
- Mandible bone defect
- Osteoclastogenesis
- Periodontitis
- Signal transduction pathways