COMP-angiopoietin-1 accelerates bone formation during distraction osteogenesis.
BACKGROUND
During distraction osteogenesis, new and highly vascularized bone is formed, with angiogenesis preceding osteogenesis. We investigated the possibility that COMP-Ang1, an angiogenic factor, may facilitate bone formation.


METHODS
Rats were divided into three groups. Control rats underwent tibial distraction without treatment. In the two remaining groups, BSA (100 microg) or COMP-Ang1 (100 microg) were injected transcutaneously into the center of the distraction zone. Using radiographic and histologic analyses, we assessed total bone volume, vascular density, and bone mineral density. Total RNA was prepared from regenerated bone and analyzed for osteogenic marker protein expression using real-time RT-PCR analysis.


RESULTS
Bone formation in the distraction gap progressed more quickly in the COMP-Ang1-treated group than in the BSA-treated group. Histological findings and immunostaining of endothelial cells for factor VIII revealed that Comp-Ang1 group animals exhibited higher levels of vascularity. NanoCT and dual-energy X-ray absorptiometry analyses revealed increased new bone formation along capillaries in the COMP-Ang1 group compared with the BSA group. Runt-related transcription factor 2 and its target genes, including bone sialoprotein, type 1 collagen, osteopontin, and osterix, were significantly upregulated in the COMP-Ang1 group.


CONCLUSIONS
Our results are consistent with previous descriptions of the positive relationship between angiogenesis and osteogenesis. In addition, our results suggest the potential use of COMP-Ang1 as a therapeutic agent for treatment of distracted limbs by enhancing angiogenesis.
Department of Biochemistry, Medical School and Research Institute of Clinical Medicine, Chonbuk National University, Jeonju, Jeonbuk, Republic of Korea.
Byung-Hyun
BH
Park
Sun Jung
SJ
Yoon
Kyu Yun
KY
Jang
Mi-Ran
MR
Kim
Hyung-Seok
HS
Lee
Ki-Bum
KB
Kim
Hyuk
H
Park
Sang Yong
SY
Lee
Ho Sung
HS
Park
Seok Tae
ST
Lim
Kyung-Jin
KJ
Song
Jung Ryul
JR
Kim
D015502:Absorptiometry, Photon; D000818:Animals; D007150:Immunohistochemistry; D010012:Osteogenesis / Q000187:drug effects*; D019857:Osteogenesis, Distraction / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013977:Tibia / Q000166:cytology / Q000000981:diagnostic imaging / Q000378:metabolism
C515576:COMP-Ang1 fusion protein; D011993:Recombinant Fusion Proteins