Site-specific tissue inhibitor of metalloproteinase-1 governs the matrix metalloproteinases-dependent degradation of crosslinked collagen scaffolds and is correlated with interleukin-10
Ye, Q., van Amerongen, M.J., Sandham, J.A., Bank, R.A., van Luyn, M.J.A., and Harmsen, M.C. (2011) Site-specific tissue inhibitor of metalloproteinase-1 governs the matrix metalloproteinases-dependent degradation of crosslinked collagen scaffolds and is correlated with interleukin-10. Journal of Tissue Engineering and Regenerative Medicine, 5 (4). pp. 264-274.
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We have previously shown that the foreign body reaction (FBR) against crosslinked collagen type I (Col-I) differs between subcutaneous and epicardial implantation sites; Col-I was quickly degraded epicardially, whereas degradation was attenuated subcutaneously. The current study set out to dissect the nature and regulation of the MMP-based degradation of implanted Col-I in mice during the FBR. Immunohistochemistry showed that MMP-2, MMP-8 and MMP-13 were present in subcutaneous and epicardial implants, whereas only MMP-9 was also present epicardially. Western blotting showed that MMP-8 and MMP-9 were mainly present in their inactive proform. In contrast, collagenase MMP-13 and gelatinase MMP-2 were the predominant active MMPs at both sites. Interestingly, the major MMP inhibitor TIMP-1 was solely observed in subcutaneous implants, which is why MMP-13 and MMP-2 are not able to degrade the collagen scaffold at the subcutaneous implantation site. Interleukin 10 (IL-10), a potent inducer of TIMP-1 expression, was also mainly detected subcutaneously; giant cells were the main source. Therefore, we surmise that IL-10, through regulation of the balance between MMPs and TIMP-1, suppresses the FBR against implanted biomaterials. Together, our findings would provide cues and clues to improve future therapies in regenerative medicine that are based on the tuned regulation of the degradation of biomaterial scaffolds.
|Item Type:||Article (Refereed Research - C1)|
|Keywords:||matrix metalloproteinase, tissue inhibitors of metalloproteinase, interleukin-10, foreign body reaction, degradation, collagen scaffold|
|Date Deposited:||09 Jun 2011 05:19|
|FoR Codes:||09 ENGINEERING > 0903 Biomedical Engineering > 090301 Biomaterials @ 100%|
|SEO Codes:||92 HEALTH > 9299 Other Health > 929999 Health not elsewhere classified @ 100%|