Journal Article

COMP-Angiopoietin1 Potentiates the Effects of Bone Morphogenic Protein-2 on Ischemic Necrosis of the Femoral Head in Rats

Zhou, Lu, Moon, Young Jae, Jang, Kyu Yun, Park, Byung-Hyun, Kim, Jung Ryul, Yoon, Sun Jung, Wagle, Sajeev, Lee, Kwang Bok

2014

Overview

Angiogenesis is considered essential for proper bone regeneration. The purpose of this investigation was to determine if a combined therapy of bone morphogenetic protein-2 (BMP-2) and cartilage oligomeric matrix protein angiopoietin-1 (COMP-Ang1) can potentiate the therapeutic effect of BMP-2 in a rat model of ischemic necrosis of the femoral head (INFH). INFH was surgically induced in the femoral head of rats, and the animals were divided into the following groups: 1) a sham-operated group (sham group), 2) a bovine serum albumin-injected group (BSA group), 3) a BMP-2-injected group (BMP-2 group), and 4) a COMP-Ang1 and BMP-2-injected group (COMP-Ang1 + BMP-2 group) (n = 20/group). Radiologic, histologic, and histomorphometric assessments were performed to assess femoral head morphology, vascular density, and bone resorption activity. Western blots and immunohistochemical staining were performed to evaluate production of BMP-related signaling proteins in C3H10T1/2 cells and tissues. Real-time RT-PCR was performed to investigate expression of the target integrin gene, and the effect of integrin on C3H10T1/2 cells was determined using a cell adhesion assay. Radiographs obtained six weeks after injection revealed better preservation of the architecture of the femoral head in the COMP-Ang1 + BMP-2 group compared with the BSA and BMP-2 groups. Histological findings indicated increased trabecular bone and vascularity and decreased osteoclast bone resorption activity in the COMP-Ang1 + BMP-2 group compared with those in the BSA and BMP-2 groups. The combination of COMP-Ang1 and BMP-2 increased phosphorylation of Smad1/3/5, p38, and Akt. Increased integrin α3 and β1 mRNA expression in the COMP-Ang1 + BMP-2 group promoted cell adhesion. These results suggest that COMP-Ang1 preserved the necrotic femoral head through the potentiation of BMP-2 signaling pathways and angiogenesis. Combination treatment with COMP-Ang1 and BMP-2 may be a clinically useful therapeutic application in INFH.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adhesion / AKT protein / Angiogenesis / Angiopoietin / Animal tissues / Animals / Biochemistry / Biocompatibility / Biology and Life Sciences / Biomedical materials / Bone (trabecular) / Bone density / Bone growth / Bone morphogenetic protein 2 / Bone Morphogenetic Protein 2 - administration & dosage / Bone Morphogenetic Protein 2 - genetics / Bone morphogenetic proteins / Bone Regeneration - drug effects / Bone resorption / Bone surgery / Bovine serum albumin / Cancellous bone / Cartilage / Cartilage oligomeric matrix protein / Cattle / Cell adhesion / Cell Culture Techniques / Clinical medicine / Cricetulus / Diabetes / Ethics / Femur / Femur Head Necrosis - diagnostic imaging / Femur Head Necrosis - drug therapy / Femur Head Necrosis - metabolism / Gangrene / Gene expression / Gene Expression Regulation, Developmental - drug effects / Health aspects / Hip joint / Humans / Immunohistochemistry / Integrins / Integrins - biosynthesis / Ischemia / Laboratory animals / Male / Matrix protein / Medical schools / Medicine / Medicine and Health Sciences / Necrosis / Neovascularization, Physiologic - drug effects / Orthopedics / Osteoclasts - drug effects / Osteogenesis - drug effects / Phosphorylation / Polymerase chain reaction / Potentiation / Proteins / Radiographs / Radiography / Rats / Recombinant Fusion Proteins - administration & dosage / Recombinant Fusion Proteins - genetics / Recombinant Proteins - administration & dosage / Recombinant Proteins - genetics / Regeneration / Regeneration (physiology) / Rodents / Serum albumin / Signaling / Vascular endothelial growth factor / Western blotting / Wound healing