A Functional RNAi Screen for Runx2-Regulated Genes Associated With Ectopic Bone Formation in Human Spinal Ligaments
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概要
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Ossification of the posterior longitudinal ligament of the spine (OPLL) is characterized by ectopic ossification in the spinal ligaments, which enlarges with time and compresses the spinal cord, resulting in serious neurological symptoms. We previously reported that Runx2 expression was enhanced in spinal ligament cells from OPLL patients (OPLL cells). To clarify genes regulated by Runx2, Runx2 expression was first enhanced by culturing primary OPLL cells in osteogenic medium (OS induction) and then inhibited by siRNAs targeted to Runx2. DNA microarray demonstrated that in addition to chondrogenic factors such as connective tissue growth factor and cartilage oligomeric matrix protein, angiopoietin-1 was also significantly increased by OS induction and decreased by siRNAs for Runx2 in OPLL cells, suggesting that these genes are regulated by Runx2. However, these changes were not observed in non-OPLL control cells (from cervical spondylotic myelopathy patients). Furthermore, Runx2 was not decreased by siRNAs for angiopoietin-1. OS induction and RNAi inhibition of angiopoietin-1 expression was also observed in osteoblasts. Both siRNAs for Runx2 and angiopoietin-1 completely inhibited aggrecan-1 expression. These results suggest that angiopoietin-1 is downstream of Runx2 in both OPLL primary cells and osteoblasts. Angiopoietin-1 may play an important role in ectopic ossification.
- 2008-03-20
著者
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Toh Satoshi
Department of Orthopedic Surgery, Hirosaki University Graduate School of Medicine
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Motomura Shigeru
Department of Pharmacology, Hirosaki University Graduate School of Medicine
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FURUKAWA Ken-Ichi
Department of Pharmacology, Hirosaki University Graduate School of Medicine
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NUMASAWA Takuya
Department of Orthopedic Surgery, School of Medicine, Hirosaki University
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Toh Satoshi
Department Of Orthopedic Surgery Hirosaki University Graduate School Of Medicine
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Kanemaru Kouta
Department Of Pharmacology Hirosaki University Graduate School Of Medicine
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Motomura Shigeru
Department Of Pharmacology Hirosaki University Graduate School Of Medicine
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Motomura Shigeru
Department Of Pharmacology Hirosaki University
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Furukawa Ken-ichi
Department Of Molecular Physiology National Cardiovascular Center Research Institute
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HARATA SEIKO
Aomori Prefectural Central Hospital
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Kudo Hajime
Department Of Pathology Hirosaki University School Of Medicine
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Kudo Hajime
Department Of Physics Faculty Of Science Science University Of Tokyo:hitachi Ltd.
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Harata Seiko
Department Of Orthopedic Surgery School Of Medicine Hirosaki University
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Harata Seiko
Department Of Orthopaedic Surgery Hirosaki University School Of Medicine
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YOKOYAMA TORU
Department of Orthopaedic Surgery, Hirosaki University School of Medicine
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Yokoyama Toru
Department Of Orthopaedic Surgery Hirosaki University Graduate School Of Medicine
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Yokoyama Toru
Department Of Mechanical Engineering Faculty Of Engineering Yokohama National University
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Kudo H
Second Department Of Pathology Hirosaki University School Of Medicine
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KUDO Hitoshi
Department of Dermatology, Graduate School of Medicine, Kyoto University
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Furukawa K
Department Of Pharmacology Hirosaki University Graduate School Of Medicine
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Motomura S
Yamanashi Medical Coll. Yamanashi Jpn
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KISHIYA Masaki
Department of Pharmacology, Hirosaki University Graduate School of Medicine
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SAWADA Toshitada
Department of Pharmacology, Hirosaki University Graduate School of Medicine
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KANEMARU Kohta
Department of Pharmacology, Hirosaki University Graduate School of Medicine
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TANAKA Sunao
Department of Orthopaedic Surgery, Hirosaki University Graduate School of Medicine
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UEYAMA Kazumasa
Hirosaki Memorial Hospital
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Sakou Takashi
Department Of Pharmacology Hirosaki University Graduate School Of Medicine
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Numasawa Takuya
Department Of Orthopaedic Surgery Hirosaki University Graduate School Of Medicine
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Ueyama Kazumasa
Department Of Orthopaedic Surgery Hirosaki Memorial Hospital
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Toh Satoshi
Department Of Orthopaedic Surgery Hirosaki University Graduate School Of Medicine
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Tsuchida S
Department Of Orthopaedic Surgery Hirosaki University Graduate School Of Medicine
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Tanaka Sunao
Department Of Orthopaedic Surgery Hirosaki University Graduate School Of Medicine
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Kishiya Masaki
Department Of Pharmacology Hirosaki University Graduate School Of Medicine
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Kudo Hitoshi
Department Of Dermatology Graduate School Of Medicine Kyoto University
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Yokoyama Toru
Department Of Orthopaedic Surgery Odate Municipal General Hospital
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Nakajima Toshiaki
Department Of Orthopaedic Surgery Hirosaki University Graduate School Of Medicine
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Yokoyama Toru
Department Of Anesthesiology And Critical Care Medicine Jichi Medical University
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Kishiya Masaki
Department Of Orthopaedic Surgery Hirosaki University Graduate School Of Medicine
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Motomura Shigeru
Department of Pharmacalogy, Respiratory Medicine and Nephrology, Hirosaki University Graduate School of Medicine
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Sawada Toshitada
Department of Orthopaedic Surgery, Hirosaki University Graduate School of Medicine
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原田 征行
Aomori Prefectural Central Hospital
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