Local delivery of COMP-angiopoietin 1 accelerates new bone formation in rat calvarial defects.

Abstract

Recombinant 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 in bone reconstruction. However, the potential of COMP-Ang1 to regenerate impaired bone and induce new bone formation has not been completely explored. In this study, male Sprague-Dawley rats underwent calvarial defect surgery and divided into two groups: scaffold treatment alone (control group) and COMP-Ang1-impregnated scaffold (COMP-Ang1 group). According to live micro-CT and histological analyses, the COMP-Ang1 group showed greater new bone formation and maturation than did the control both four and eight weeks after surgery. The values of bone volume, bone mineral density, and bone surface were also higher in the COMP-Ang1 group than in the control at the same weeks after surgery. In addition, the delivery of COMP-Ang1 facilitated significantly the expression of osteoblast-specific markers such as runt-related transcription factor 2 (p < 0.001), osterix (p < 0.001), bone morphogenetic protein-2 (p < 0.001), alkaline phosphatase (p < 0.01), osteocalcin (p < 0.001), and type I collagen (p < 0.05) in newly formed bone, compared with the control. Immunohistochemistric assay supported the COMP-Ang1-facilitated induction of bone-specific markers. Furthermore, COMP-Ang1 augmented the mRNA expression of angiogenic factors, especially of platelet endothelial cell adhesion molecule 1, stromal cell-derived factor 1, and Tie-2 in the defect site. Our current findings demonstrate for the first time that a local delivery of recombinant COMP-Ang1 promotes bone formation in calvarial defects, which is coupled with enhanced angiogenesis and chemoattraction.