The role of collagen receptors Endo180 and DDR-2 in the foreign body reaction against non-crosslinked collagen and gelatin.
Despite the use of collagen-derived scaffolds in regenerative medicine, little is known about the degradation mechanisms of these scaffolds in vivo. Non-crosslinked dermal sheep (NDSC) and gelatin disks were implanted subcutaneously in mice. NDSC disks showed a very low degradation rate, despite the presence of high numbers of macrophages and the influx of neutrophils. This was attributed to the presence of the matrix metalloproteinase inhibitor TIMP-1. The limited degradation occurred mainly in the later stages of the foreign body reaction, and could be attributed to (1) phagocytosis by macrophages due to a co-expression of Endo180 and MT1-MMP on these cells (intracellular degradation) and (2) the presence of MMP-13 due to an upregulation of the expression of the DDR-2 receptor (extracellular degradation). In contrast, gelatin disks degraded quickly, due to the efficient formation of large giant cells as well as the presence of MMP-13; the inhibitor TIMP-1 was absent. The DDR-2 receptor was not expressed in the gelatin disks. Endo180 and MT1-MMP were expressed, but at most times no co-expression was seen. We conclude that the physical state of collagen (native or denatured) had a dramatic outcome on the degradation rate and provoked a completely different foreign body reaction.
Department of Pathology & Medical Biology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands. qingsongye@hotmail.com
Qingsong
Q
Ye
Martin C
MC
Harmsen
Yijin
Y
Ren
Ruud A
RA
Bank
D000818:Animals; D003094:Collagen / Q000737:chemistry / Q000276:immunology*; D000070818:Discoidin Domain Receptors; D005549:Foreign-Body Reaction / Q000276:immunology / Q000378:metabolism*; D005780:Gelatin / Q000737:chemistry / Q000276:immunology*; D015726:Giant Cells / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D011975:Receptors, Mitogen / Q000378:metabolism*; D054457:Tissue Scaffolds
C408294:Endo180; D011975:Receptors, Mitogen; D005780:Gelatin; D003094:Collagen; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases; D053509:Matrix Metalloproteinase 13; D053511:Matrix Metalloproteinase 14