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인간 추간판 세포에서 파미드로네이트의 기질 생성 및 세포 사멸 효과

Other Titles
 Anabolic and Anti-apoptotic Effects of Pamidonate on Human Intervertebral Disc Cells in Vitro 
Authors
 전지애  ;  김향  ;  문성환  ;  윤성환  ;  신규호  ;  이환모  ;  김학선  ;  박시영  ;  이광일  ;  권언혜 
Citation
 Korean Journal of Bone Metabolism (대한골대사학회지), Vol.11(2) : 121-128, 2004 
Journal Title
 Korean Journal of Bone Metabolism (대한골대사학회지) 
ISSN
 1598-107X 
Issue Date
2004
Keywords
Intervertebral disc cells ; Apoptosis ; Bisphosphonate ; Proteoglycan
Abstract
Background:As potent inhibitors of bone resorption, bisphosphonates (BPs) are widely used for the treatment of bone disorders that are due to increased osteoclast activity i.e. postmenopausal osteoporosis, Paget´s disease, tumoral bone disease. BPs are also broad-spectrum matrix metalloproteinase (MMP) inhibitors which involves cation chelation. Apoptosis appears to provide an important mechanism that contribute to the death of disc cells and thus disc degeneration. In articular chondrocytes, bPs appear to prevent dexamethasone induced growth retardation and apoptosis. Accordingly, the objective of this study is to investigate the effect of pamidronate, N-containing bPs, on human intervertebral disc cells in terms of cellular proliferation, matrix synthesis, mRNA expression of matrix components, apoptosis, and mRNA expression of MMP. Methods: Human disc tissues were obtained from three patients with degenerative disc disease. Intervertebral disc cells were isolated by sequential exzymatic method. Apoptosis was induced by using serum starvation method with 1% FBS. Each culture was allocated to 1) control cultures with 10% FBS; 2) experimental cultures in 1% FBS without pamidronate; 3) experimental cultures with 1% FBS with various dose of pamidronate (10-¹², 10-9, 10-6M).[³H]-Thymidine for DNA synthesis and [³ⁿS]-Sulfare incorporation for proteoglycan synthesis were performed. The cells were stained Propidium Idodide Buffer to detect apoptotic cells and then analyzed by flow cytometry. Reverse transcroption polymerase chain reaction for mRNA of beta-actin, collagen type Ⅰ, collagen type Ⅱ, aggrecan, MMP-1, MMP-3, and MMP-13 was performed. Results: Disc cell cultures with various concentrations of pamidronate (10-¹², 10-9, 10-6M) showed no significant increase in DNA synthesis compared to control culture. However disc cell cultures with pamidronate showed significant increase in proteoglycan synthesis, 40% increase with 10-9M pamidronate (p<0.05). compaater to control cultures Disc cells with various dose of pamidronate showed similar patterns of mRNA expression of collagen type Ⅰ,Ⅱ, aggrecan compared to culture wihout pamidronate, In serum starved condition (1%FBS), pamidronate with concentration of 10-¹² to 10-6M demonstrated anti-apoptic effecr. Cultures with 1% FBS showed upregulation of MMP-1, MMP-3, MMP-13 mRNA expression, while cultures with given dose of pamidronate showed no change in the expression of MMPs mRNA. Conclusion: Pamidronate, N-containing BP has anabolic and anti-apoptotic, effects on intervertebral disc cells and their matrix.
Files in This Item:
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Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Orthopedic Surgery (정형외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hak Sun(김학선) ORCID logo https://orcid.org/0000-0002-8330-4688
Moon, Seong Hwan(문성환)
Park, Si Young(박시영)
Shin, Kyoo Ho(신규호)
Lee, Hwan Mo(이환모) ORCID logo https://orcid.org/0000-0002-5405-3832
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/112194
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