Universität zu Köln

Gruenherz, Lisanne, Prein, Carina, Winkler, Thomas, Kirsch, Manuela, Hopfner, Ursula, Streichert, Thomas, Clausen-Schaumann, Hauke ORCID: 0000-0002-9413-0310, Zustin, Jozef, Kirchhof, Kristin, Morlock, Michael M., Machens, Hans-Guenter and Schilling, Arndt Friedrich (2020). Osteoidosis leads to altered differentiation and function of osteoclasts. J. Cell. Mol. Med., 24 (10). S. 5665 - 5675. HOBOKEN: WILEY. ISSN 1582-4934

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Abstract

In patients with osteomalacia, a defect in bone mineralization leads to changed characteristics of the bone surface. Considering that the properties of the surrounding matrix influence function and differentiation of cells, we aimed to investigate the effect of osteoidosis on differentiation and function of osteoclasts. Based on osteomalacic bone biopsies, a model for osteoidosis in vitro (OIV) was established. Peripheral blood mononuclear cells were differentiated to osteoclasts on mineralized surfaces (MS) as internal control and on OIV. We observed a significantly reduced number of osteoclasts and surface resorption on OIV. Atomic force microscopy revealed a significant effect of the altered degree of mineralization on surface mechanics and an unmasking of collagen fibres on the surface. Indeed, coating of MS with RGD peptides mimicked the resorption phenotype observed in OIV, suggesting that the altered differentiation of osteoclasts on OIV might be associated with an interaction of the cells with amino acid sequences of unmasked extracellular matrix proteins containing RGD sequences. Transcriptome analysis uncovered a strong significant up-regulation of transmembrane glycoprotein TROP2 in osteoclastic cultures on OIV. TROP2 expression on OIV was also confirmed on the protein level and found on the bone surface of patients with osteomalacia. Taken together, our results show a direct influence of the mineralization state of the extracellular matrix surface on differentiation and function of osteoclasts on this surface which may be important for the pathophysiology of osteomalacia and other bone disorders with changed ratio of osteoid to bone.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Gruenherz, Lisanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Prein, Carina UNSPECIFIED UNSPECIFIED UNSPECIFIED Winkler, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Kirsch, Manuela UNSPECIFIED UNSPECIFIED UNSPECIFIED Hopfner, Ursula UNSPECIFIED UNSPECIFIED UNSPECIFIED Streichert, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Clausen-Schaumann, Hauke UNSPECIFIED orcid.org/0000-0002-9413-0310 UNSPECIFIED Zustin, Jozef UNSPECIFIED UNSPECIFIED UNSPECIFIED Kirchhof, Kristin UNSPECIFIED UNSPECIFIED UNSPECIFIED Morlock, Michael M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Machens, Hans-Guenter UNSPECIFIED UNSPECIFIED UNSPECIFIED Schilling, Arndt Friedrich UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-337300
DOI:	10.1111/jcmm.15227
Journal or Publication Title:	J. Cell. Mol. Med.
Volume:	24
Number:	10
Page Range:	S. 5665 - 5675
Date:	2020
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1582-4934
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MECHANICAL-PROPERTIES; BONE; PROLIFERATION; STEM; BIORESORPTION; BIOMATERIALS; INHIBITION; ECHISTATIN; RESORPTION; DENSITY Multiple languages Cell Biology; Medicine, Research & Experimental Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/33730