Abstract
Intervertebral disc (IVD) degeneration is the most common cause of back pain. Presently there is no medical treatment, leaving surgery as the only offered option. Here we evaluate the potential of Link-N to promote extracellular matrix regeneration in human IVDs. Human disc cells cultured in alginate and intact human discs were exposed to a combination of Link-N and ³⁵SO₄ in the presence or absence of interleukin (IL)-1, and the effect on proteoglycan synthesis was evaluated. In addition, message levels of aggrecan, matrix metalloproteinase (MMP)-3, MMP-13, a Disintegrin And Metalloproteinase with Thrombospondin Motifs (ADAMTS)-4 and ADAMTS-5 were evaluated in alginate cultures. Human disc cells responded in a dose dependent manner with maximal proteoglycan synthesis at 1 µg/mL Link-N. Link-N treatment also induced proteoglycan synthesis in intact human discs, and a prolonged effect was found up to one week after Link-N treatment. Message levels of proteinases were decreased by Link-N in the presence of IL-1. Thus, Link-N can promote proteoglycan synthesis and deplete proteinase expression in adult human discs. Link-N could therefore be a promising candidate for biologically-induced disc repair, and could provide an alternative to surgical intervention for early stage disc degeneration.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ADAM Proteins / genetics
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ADAM Proteins / metabolism
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ADAMTS4 Protein
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ADAMTS5 Protein
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Adolescent
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Adult
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Aged
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Aggrecans / genetics
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Aggrecans / metabolism
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Animals
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Cattle
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Extracellular Matrix / metabolism
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Extracellular Matrix Proteins / biosynthesis
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Extracellular Matrix Proteins / chemistry
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Extracellular Matrix Proteins / pharmacology*
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Female
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Humans
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Interleukin-1 / genetics
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Interleukin-1 / metabolism
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Intervertebral Disc / drug effects
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Intervertebral Disc / metabolism*
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Intervertebral Disc Degeneration / metabolism*
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Male
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Matrix Metalloproteinase 13 / genetics
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Matrix Metalloproteinase 13 / metabolism
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Matrix Metalloproteinase 3 / genetics
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Matrix Metalloproteinase 3 / metabolism
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Middle Aged
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Procollagen N-Endopeptidase / genetics
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Procollagen N-Endopeptidase / metabolism
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Protein Structure, Tertiary
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Proteoglycans / biosynthesis
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Proteoglycans / chemistry
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Proteoglycans / pharmacology*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
Substances
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Aggrecans
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Extracellular Matrix Proteins
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Interleukin-1
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Proteoglycans
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RNA, Messenger
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link protein
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ADAM Proteins
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ADAMTS5 Protein
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ADAMTS5 protein, human
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MMP13 protein, human
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Matrix Metalloproteinase 13
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Procollagen N-Endopeptidase
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MMP3 protein, human
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Matrix Metalloproteinase 3
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ADAMTS4 Protein
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ADAMTS4 protein, human