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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, Vol. 24, No. 10, 05.2020, p. 5665-5674.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Grünherz, L, Prein, C, Winkler, T, Kirsch, M, Hopfner, U, Streichert, T, Clausen-Schaumann, H, Zustin, J, Kirchhof, K, Morlock, MM, Machens, H-G & Schilling, AF 2020, 'Osteoidosis leads to altered differentiation and function of osteoclasts', J CELL MOL MED, vol. 24, no. 10, pp. 5665-5674. https://doi.org/10.1111/jcmm.15227

APA

Grünherz, L., Prein, C., Winkler, T., Kirsch, M., Hopfner, U., Streichert, T., Clausen-Schaumann, H., Zustin, J., Kirchhof, K., Morlock, M. M., Machens, H-G., & Schilling, A. F. (2020). Osteoidosis leads to altered differentiation and function of osteoclasts. J CELL MOL MED, 24(10), 5665-5674. https://doi.org/10.1111/jcmm.15227

Vancouver

Grünherz L, Prein C, Winkler T, Kirsch M, Hopfner U, Streichert T et al. Osteoidosis leads to altered differentiation and function of osteoclasts. J CELL MOL MED. 2020 May;24(10):5665-5674. https://doi.org/10.1111/jcmm.15227

Bibtex

@article{89245a46cfc348b48ecd083826e332f5,
title = "Osteoidosis leads to altered differentiation and function of osteoclasts",
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.",
author = "Lisanne Gr{\"u}nherz and Carina Prein and Thomas Winkler and Manuela Kirsch and Ursula Hopfner and Thomas Streichert and Hauke Clausen-Schaumann and Jozef Zustin and Kristin Kirchhof and Morlock, {Michael M} and Hans-G{\"u}nter Machens and Schilling, {Arndt Friedrich}",
note = "{\textcopyright} 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.",
year = "2020",
month = may,
doi = "10.1111/jcmm.15227",
language = "English",
volume = "24",
pages = "5665--5674",
journal = "J CELL MOL MED",
issn = "1582-1838",
publisher = "Wiley-Blackwell",
number = "10",

}

RIS

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 -