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Pamidronate Down-regulates Tumor Necrosis Factor-alpha Induced Matrix Metalloproteinases Expression in Human Intervertebral Disc Cells

 Young-Mi Kang  ;  Seong-Hwan Hong  ;  Jae-Ho Yang  ;  Jin-Cheol Oh  ;  Jin-Oh Park  ;  Byung Ho Lee  ;  Sang-Yoon Lee  ;  Hak-Sun Kim  ;  Hwan-Mo Lee  ;  Seong-Hwan Moon 
 Journal of Bone Metabolism, Vol.23(3) : 165-173, 2016 
Journal Title
 Journal of Bone Metabolism 
Issue Date
Collagen ; Intervertebral disc ; Matrix metalloproteinases ; Pamidronate ; Tumor necrosis factor-alpha
BACKGROUND: N-containing bisphosphonates (BPs), such as pamidronate and risedronate, can inhibit osteoclastic function and reduce osteoclast number by inducing apoptotic cell death in osteoclasts. The aim of this study is to demonstrate the effect of pamidronate, second generation nitrogen-containing BPs and to elucidate matrix metallo-proteinases (MMPs) mRNA expression under serum starvation and/or tumor necrosis factor alpha (TNF-α) stimulation on metabolism of intervertebral disc (IVD) cells in vitro. METHODS: Firstly, to test the effect of pamidronate on IVD cells in vitro, various concentrations (10(-12), 10(-10), 10(-8), and 10(-6) M) of pamidronate were administered to IVD cells. Then DNA and proteoglycan synthesis were measured and messenger RNA (mRNA) expressions of type I collagen, type II collagen, and aggrecan were analyzed. Secondly, to elucidate the expression of MMPs mRNA in human IVD cells under the lower serum status, IVD cells were cultivated in full serum or 1% serum. Thirdly, to elucidate the expression of MMPs mRNA in IVD cells under the stimulation of 1% serum and TNF-α (10 ng/mL) In this study, IVD cells were cultivated in three dimensional alginate bead. RESULTS: Under the lower serum culture, IVD cells in alginate beads showed upregulation of MMP 2, 3, 9, 13 mRNA. The cells in lower serum and TNF-α also demonstrated upregulation of MMP-2, 3, 9, and 13 mRNA. The cells with various doses of pamidronate and lower serum and TNF-α were reveled partial down-regulation of MMPs. CONCLUSIONS: Pamidronate, N-containing second generation BPs, was safe in metabolism of IVD in vitro maintaining chondrogenic phenotype and matrix synthesis, and down-regulated TNF-α induced MMPs expression.
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1. College of Medicine (의과대학) > Dept. of Orthopedic Surgery (정형외과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Young Mi(강영미) ORCID logo https://orcid.org/0000-0002-7686-6316
Kim, Hak Sun(김학선) ORCID logo https://orcid.org/0000-0002-8330-4688
Moon, Seong Hwan(문성환)
Park, Jin Oh(박진오)
Yang, Jae Ho(양재호) ORCID logo https://orcid.org/0000-0001-7421-2805
Oh, Jin-Cheol(오진철)
Lee, Sang-Yun(이상윤)
Lee, Hwan Mo(이환모) ORCID logo https://orcid.org/0000-0002-5405-3832
Hong, Seong-Hwan(홍성환)
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