title: Phagocytosis of Collagen Fibrils by Fibroblasts In Vivo Is Independent of the uPARAP/Endo180 Receptor.
abstract: As a crucial step in ECM remodeling, collagen degradation occurs through different processes, including both extracellular and intracellular degradation. The extracellular pathways of collagen degradation require secretion of collagenolytic proteases, whereas intracellular collagen degradation occurs in the lysosomal compartment after uptake, involving either pre-cleaved or intact fibrillar collagen. The endocytic collagen receptor uPARAP/Endo180 plays an important role in internalization of large collagen degradation products, whereas its role in the phagocytosis of fibrillar collagen has been debated. In fact, the role of this receptor in regular collagen phagocytosis in vivo has not been established. In this study, we have studied the role of uPARAP in the phagocytosis of collagen fibrils in vivo by analyzing different connective tissues of mice lacking uPARAP. Using transmission electron microscopy (TEM), we found that fibroblasts in the periosteum of tibia and calvaria, as well as in the periodontal ligament of molar and incisor, phagocytosed collagen fibrils independently of uPARAP. Quantification of phagocytosed collagen in the periodontal ligament of uPARAP-deficient mice and controls revealed no difference in the amount of fibrillar collagen taken up by uPARAP-deficient mice. The findings show that under in vivo conditions uPARAP does not play a role in the phagocytic uptake of collagen fibrils by fibroblasts. Consequently, the cellular uptake of collagen fibrils and collagen cleavage products probably occurs through fundamentally different pathways. J. Cell. Biochem. 118: 1590-1595, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Oral Cell Biology and Functional Anatomy, MOVE Research Institute, University of Amsterdam and VU University, Academic Center for Dentistry Amsterdam (ACTA), Amsterdam, The Netherlands.
authors.forename: Sara
authors.initials: S
authors.lastname: Sprangers
authors.affiliation: The Finsen Laboratory, University of Copenhagen, Rigshospitalet/Biotech Research and Innovation Center, Copenhagen, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Behrendt
authors.affiliation: The Finsen Laboratory, University of Copenhagen, Rigshospitalet/Biotech Research and Innovation Center, Copenhagen, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Engelholm
authors.affiliation: Department of Oral Cell Biology and Functional Anatomy, MOVE Research Institute, University of Amsterdam and VU University, Academic Center for Dentistry Amsterdam (ACTA), Amsterdam, The Netherlands.
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Oral Cell Biology and Functional Anatomy, MOVE Research Institute, University of Amsterdam and VU University, Academic Center for Dentistry Amsterdam (ACTA), Amsterdam, The Netherlands.
authors.forename: Vincent
authors.initials: V
authors.lastname: Everts
mesh_terms: D000818:Animals; D005109:Extracellular Matrix / Q000378:metabolism; D024022:Fibrillar Collagens / Q000378:metabolism*; D005347:Fibroblasts / Q000502:physiology* / Q000648:ultrastructure; D007180:Incisor / Q000166:cytology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008963:Molar / Q000166:cytology; D010513:Periodontal Ligament / Q000166:cytology*; D010521:Periosteum / Q000166:cytology*; D010587:Phagocytosis; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D012886:Skull / Q000166:cytology; D013977:Tibia / Q000166:cytology
chemical_list: D024022:Fibrillar Collagens; D008562:Membrane Glycoproteins; C474081:Mrc2 protein, mouse; D011956:Receptors, Cell Surface
keywords: COLLAGEN PHAGOCYTOSIS; FIBROBLAST; TRANSMISSION ELECTRON MICROSCOPY; uPARAP