Original Article
J Rheum Dis 2012; 19(2): 82-90
Published online April 30, 2012
© Korean College of Rheumatology
COMP-Angiopoietin-1 Stimulates Synovial Proliferation but Suppresses Osteoclast by Enhancing Angiogenesis and Osteoblast Maturation in Collagen-Induced Arthritis
Correspondence to : Sang-Il Lee
Objective. Angiopoietin-1 (Ang1) is a potent angiogenic factor that can increase synovial angiogenesis and also enhance osteoblast maturation and bone formation. However, its role in rheumatoid arthritis (RA) has not been well documented. Thus, we investigated roles of Ang1 in collagen-induced arthritis (CIA).
Methods. A recombinant adenovirus carrying the gene that encodes either cartilage oligomeric matrix protein (AdCOMP)-Ang1 (a modified form of Ang1) or LacZ (AdLacZ) was injected intravenously into CIA mice. Clinical, radiological, histopathological, and immunofluorescent analyses were performed. Serum levels of receptor activators of nuclear factor ՊB ligand (RANKL) and osteoprotegerin (OPG) and expression of osteoblast maturation genes were analyzed.
Results. AdCOMP-Ang1-injected mice developed more severe inflammation than the AdLacZ-injected mice. However, there were no significant differences in cartilage damage and bone erosion. More PECAM-1-positive blood vessels were seen in the synovium of the AdCOMP-Ang1-injected mice than in those injected with AdLacZ. Interestingly, a lower number of TRAP-positive osteoclasts were observed in AdCOMP-Ang1-injected CIA mice than in the AdLacZ group when comparing sections obtained from joints showing similar synovial proliferation. The serum OPG/RANKL ratio and expression of osteoblast maturation genes, such as runt-related transcription factor 2, bone sialoprotein, type 1 collagen, osteopontin, and osterix, were significantly upregulated in the AdCOMP-Ang1 group.
Conclusion. COMP-Ang1 facilitates arthritis onset and increases synovial inflammation, but enhances osteoblast maturation, which in turn inhibits osteoclastogenesis by increasing the OPG/RANKL ratio in CIA. Our results suggest that careful investigation is necessary to delineate the possible therapeutic use of COMP-Ang1 as an adjunctive agent, in combination with anti-inflammatory therapies, for the prevention of bone destruction in RA.
Keywords Rheumatoid arthritis, Collagen-induced arthritis, COMP-Ang1, Osteoclasts, Osteoblasts
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Original Article
J Rheum Dis 2012; 19(2): 82-90
Published online April 30, 2012
Copyright © Korean College of Rheumatology.
COMP-Angiopoietin-1 Stimulates Synovial Proliferation but Suppresses Osteoclast by Enhancing Angiogenesis and Osteoblast Maturation in Collagen-Induced Arthritis
Yong-Geun Jeong1,#, Hyun-Ok Kim1,#, Hye Song Lim1, Young-Sool Hah2, Hee Young Cho2, Jiahua Yu3, Byung-Hyun Park3, Gou Young Koh4, Sang-Il Lee1
Department of Internal Medicine and Institute of Health Science, Gyeongsang National University School of Medicine1, Clinical Research Institute, Gyeongsang National University Hospital2, Jinju, Department of Biochemistry, Medical School and Diabetes Research Center, Chonbuk National University3, Jeonju, National Research Laboratory of Vascular Biology and Department of Biological Sciences, Korea Advanced Institute of Science and Technology4, Daejeon, Korea
Correspondence to:Sang-Il Lee
Abstract
Objective. Angiopoietin-1 (Ang1) is a potent angiogenic factor that can increase synovial angiogenesis and also enhance osteoblast maturation and bone formation. However, its role in rheumatoid arthritis (RA) has not been well documented. Thus, we investigated roles of Ang1 in collagen-induced arthritis (CIA).
Methods. A recombinant adenovirus carrying the gene that encodes either cartilage oligomeric matrix protein (AdCOMP)-Ang1 (a modified form of Ang1) or LacZ (AdLacZ) was injected intravenously into CIA mice. Clinical, radiological, histopathological, and immunofluorescent analyses were performed. Serum levels of receptor activators of nuclear factor ՊB ligand (RANKL) and osteoprotegerin (OPG) and expression of osteoblast maturation genes were analyzed.
Results. AdCOMP-Ang1-injected mice developed more severe inflammation than the AdLacZ-injected mice. However, there were no significant differences in cartilage damage and bone erosion. More PECAM-1-positive blood vessels were seen in the synovium of the AdCOMP-Ang1-injected mice than in those injected with AdLacZ. Interestingly, a lower number of TRAP-positive osteoclasts were observed in AdCOMP-Ang1-injected CIA mice than in the AdLacZ group when comparing sections obtained from joints showing similar synovial proliferation. The serum OPG/RANKL ratio and expression of osteoblast maturation genes, such as runt-related transcription factor 2, bone sialoprotein, type 1 collagen, osteopontin, and osterix, were significantly upregulated in the AdCOMP-Ang1 group.
Conclusion. COMP-Ang1 facilitates arthritis onset and increases synovial inflammation, but enhances osteoblast maturation, which in turn inhibits osteoclastogenesis by increasing the OPG/RANKL ratio in CIA. Our results suggest that careful investigation is necessary to delineate the possible therapeutic use of COMP-Ang1 as an adjunctive agent, in combination with anti-inflammatory therapies, for the prevention of bone destruction in RA.
Keywords: Rheumatoid arthritis, Collagen-induced arthritis, COMP-Ang1, Osteoclasts, Osteoblasts
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