Osteoidosis leads to altered differentiation and function of osteoclasts
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Osteoidosis leads to altered differentiation and function of osteoclasts. / Grünherz, Lisanne; Prein, Carina; Winkler, Thomas; Kirsch, Manuela; Hopfner, Ursula; Streichert, Thomas; Clausen-Schaumann, Hauke; Zustin, Jozef; Kirchhof, Kristin; Morlock, Michael M; Machens, Hans-Günter; Schilling, Arndt Friedrich.
in: J CELL MOL MED, Jahrgang 24, Nr. 10, 05.2020, S. 5665-5674.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Osteoidosis leads to altered differentiation and function of osteoclasts
AU - Grünherz, Lisanne
AU - Prein, Carina
AU - Winkler, Thomas
AU - Kirsch, Manuela
AU - Hopfner, Ursula
AU - Streichert, Thomas
AU - Clausen-Schaumann, Hauke
AU - Zustin, Jozef
AU - Kirchhof, Kristin
AU - Morlock, Michael M
AU - Machens, Hans-Günter
AU - Schilling, Arndt Friedrich
N1 - © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
PY - 2020/5
Y1 - 2020/5
N2 - 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.
AB - 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.
U2 - 10.1111/jcmm.15227
DO - 10.1111/jcmm.15227
M3 - SCORING: Journal article
C2 - 32283567
VL - 24
SP - 5665
EP - 5674
JO - J CELL MOL MED
JF - J CELL MOL MED
SN - 1582-1838
IS - 10
ER -