title: Early reversal cells in adult human bone remodeling: osteoblastic nature, catabolic functions and interactions with osteoclasts.
abstract: The mechanism coupling bone resorption and formation is a burning question that remains incompletely answered through the current investigations on osteoclasts and osteoblasts. An attractive hypothesis is that the reversal cells are likely mediators of this coupling. Their nature is a big matter of debate. The present study performed on human cancellous bone is the first one combining in situ hybridization and immunohistochemistry to demonstrate their osteoblastic nature. It shows that the Runx2 and CD56 immunoreactive reversal cells appear to take up TRAcP released by neighboring osteoclasts. Earlier preclinical studies indicate that reversal cells degrade the organic matrix left behind by the osteoclasts and that this degradation is crucial for the initiation of the subsequent bone formation. To our knowledge, this study is the first addressing these catabolic activities in adult human bone through electron microscopy and analysis of molecular markers. Periosteoclastic reversal cells show direct contacts with the osteoclasts and with the demineralized resorption debris. These early reversal cells show (1) ¾-collagen fragments typically generated by extracellular collagenases of the MMP family, (2) MMP-13 (collagenase-3) and (3) the endocytic collagen receptor uPARAP/Endo180. The prevalence of these markers was lower in the later reversal cells, which are located near the osteoid surfaces and morphologically resemble mature bone-forming osteoblasts. In conclusion, this study demonstrates that reversal cells colonizing bone surfaces right after resorption are osteoblast-lineage cells, and extends to adult human bone remodeling their role in rendering eroded surfaces osteogenic.
authors: Department of Clinical Cell Biology (KCB), Vejle Hospital - Lillebaelt Hospital, IRS, University of Southern Denmark, Kabbeltoft 25, 7100, Vejle, Denmark.|Faculty of Science, Helwan University, Helwan, Egypt.
authors: Mohamed Essameldin
authors: ME
authors: Abdelgawad
authors: Department of Clinical Cell Biology (KCB), Vejle Hospital - Lillebaelt Hospital, IRS, University of Southern Denmark, Kabbeltoft 25, 7100, Vejle, Denmark. Jean-marie.delaisse@rsyd.dk.
authors: Jean-Marie
authors: JM
authors: Delaisse
authors: Department of Clinical Cell Biology (KCB), Vejle Hospital - Lillebaelt Hospital, IRS, University of Southern Denmark, Kabbeltoft 25, 7100, Vejle, Denmark.|Division of Hematology, Department of Internal Medicine, Vejle Hospital - Lillebaelt Hospital, IRS, University of Southern Denmark, Vejle, Denmark.
authors: Maja
authors: M
authors: Hinge
authors: Department of Clinical Cell Biology (KCB), Vejle Hospital - Lillebaelt Hospital, IRS, University of Southern Denmark, Kabbeltoft 25, 7100, Vejle, Denmark.
authors: Pia Rosgaard
authors: PR
authors: Jensen
authors: Department of Clinical Cell Biology (KCB), Vejle Hospital - Lillebaelt Hospital, IRS, University of Southern Denmark, Kabbeltoft 25, 7100, Vejle, Denmark.
authors: Ragad Walid
authors: RW
authors: Alnaimi
authors: Breast and Endocrine Section, Department of Surgery, Aarhus University Hospital, Aarhus, Denmark.
authors: Lars
authors: L
authors: Rolighed
authors: The Finsen Laboratory, Rigshospitalet/Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
authors: Lars H
authors: LH
authors: Engelholm
authors: Department of Clinical Pathology, Odense University Hospital, Odense, Denmark.
authors: Niels
authors: N
authors: Marcussen
authors: Department of Clinical Cell Biology (KCB), Vejle Hospital - Lillebaelt Hospital, IRS, University of Southern Denmark, Kabbeltoft 25, 7100, Vejle, Denmark. Thomas.levin.andersen@rsyd.dk.
authors: Thomas Levin
authors: TL
authors: Andersen
mesh_terms: D000328:Adult; D000368:Aged; D016723:Bone Remodeling; D005260:Female; D006801:Humans; D049950:Hyperparathyroidism, Primary / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D010006:Osteoblasts / Q000378:metabolism* / Q000473:pathology; D010010:Osteoclasts / Q000378:metabolism* / Q000473:pathology
keywords: Catabolism; Collagenolysis; Interaction; Osteoblast; Osteoclast; Reversal cells; Reversal phase