Introduction
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Introduction• High temperature requirement serine protease A1 (HTRA1) has
been associated as a potential gene for IDD in human gene
association study [1, 2].
• Hypothesis. Injection of clinically-relevant catabolic enzymes will
induce a shift from anabolic to catabolic metabolism.
• The aim was to develop a model of enzyme-induced IDD that
could be used for efficient investigation of therapeutic treatment
options in order to better mimic the clinical outcome of IDD in
humans.
• Three enzymes were tested in a first approach (HTRA1, ADAMTS-4
and MMP-3) at ~1000 x hyper-physiological doses.[1] A. N. Tiaden, M. Klawitter, V. Lux, A. Mirsaidi, et al., J Biol Chem 287, 21335-45 (2012).[2] T. Urano, K. Narusawa, S. Kobayashi, M. Shiraki, et al., J Bone Miner Metab 28, 220-6 (2010).
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Conclusion Enzyme concentrations at about a factor 1,000 x higher than
found at physiological level induced a catabolic response at the RNA level (ADMTS-4 and MMP-13).
However, no evidence for a clear degenerative pattern could be found and there was no evidence for a cavity comparable to papain (biochemistry and histology) after 8 days of culture.
$$$ Costs of enzymes (MMP-3 and ADAMTS-4) are very high compared to more catabolic enzymes such as papain and trypsin and degenerate effects are too modest.