COMP-Ang1 prevents periodontitic damages and enhances mandible bone growth in an experimental animal model.
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.
Cluster for Craniofacial Development & Regeneration Research, Institute of Oral Biosciences (BK21 program) and School of Dentistry, Chonbuk National University, Jeonju 54896, South Korea.
Govinda
G
Bhattarai
Cluster for Craniofacial Development & Regeneration Research, Institute of Oral Biosciences (BK21 program) and School of Dentistry, Chonbuk National University, Jeonju 54896, South Korea; Department of Bioactive Material Sciences, Research Center of Bioactive Materials, Chonbuk National University, Jeonju 54896, South Korea.
Sung-Ho
SH
Kook
Chonnam National University Dental Hospital, Kwangju 61186, South Korea.
Jae-Hwan
JH
Kim
Cluster for Craniofacial Development & Regeneration Research, Institute of Oral Biosciences (BK21 program) and School of Dentistry, Chonbuk National University, Jeonju 54896, South Korea.
Sher Bahadur
SB
Poudel
School of Dentistry and Dental Research Institute, Seoul National University, Seoul 08826, South Korea.
Shin-Saeng
SS
Lim
Research Institute of Biotechnology, Dongguk University, Seoul 04620, South Korea.
Young-Kwon
YK
Seo
Cluster for Craniofacial Development & Regeneration Research, Institute of Oral Biosciences (BK21 program) and School of Dentistry, Chonbuk National University, Jeonju 54896, South Korea; Department of Bioactive Material Sciences, Research Center of Bioactive Materials, Chonbuk National University, Jeonju 54896, South Korea. Electronic address: leejc88@jbnu.ac.kr.
Jeong-Chae
JC
Lee
D000818:Animals; D001846:Bone Development / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D008334:Mandible / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000254:growth & development*; D051379:Mice; D023421:Models, Animal; D010518:Periodontitis / Q000000981:diagnostic imaging / Q000188:drug therapy*; D000067996:RAW 264.7 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use
C515576:COMP-Ang1 fusion protein; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins
Bone regeneration; COMP-Ang1; Mandible bone defect; Osteoclastogenesis; Periodontitis; Signal transduction pathways