the efficacy of link n as a mediator of repair in a rabbit model of intervertebral disc degeneration链接的功效n作为调停者的修复兔椎间盘退变模型.pdfVIP

Mwale et al. Arthritis Research Therapy 2011, 13:R120 /content/13/4/R120 RESEARCH ARTICLE Open Access The efficacy of Link N as a mediator of repair in a rabbit model of intervertebral disc degeneration 1,2* 3 3 2 3 3 Fackson Mwale , Koichi Masuda , Rajeswari Pichika , Laura M Epure , Tomoaki Yoshikawa , Aseem Hemmad , Peter J Roughley4 and John Antoniou1,2 Abstract Introduction: Intervertebral disc (IVD) degeneration is associated with proteolytic degradation of the extracellular matrix, and its repair requires both the production of extracellular matrix and the downregulation of proteinase activity. These properties are associated with several growth factors. However, the use of growth factors in clinical practice is limited by their high cost. This cost can be circumvented using synthetic peptides, such as Link N, which can stimulate the synthesis of proteoglycan and collagen by IVD cells in vitro. The purpose of the present study was to evaluate the effect of Link N in vivo in a rabbit model of IVD degeneration. Methods: New Zealand white rabbits received annular puncture in two lumbar discs. Two weeks after puncture, both punctured discs of each rabbit were injected with either Link N or saline. After 2 weeks, nine rabbits were euthanized and the annulus fibrosus (AF) and nucleus pulposus (NP) of Link N-injected and saline-injected IVDs were removed and used to prepare total RNA. Following reverse transcription, quantitative PCR was performed for aggrecan, COL2A1, COL1A1, ADAMTS-4, ADAMTS-5 and MMP-3. After 12 weeks, 19 rabbits were euthanized and the injected IVDs were removed for biochemical and histological analysis. Proteinase K digests were analyzed for DNA and sulfated