Open AccessOsteoidosis leads to altered differentiation and function of osteoclasts
Author(s) -
Grünherz Lisanne,
Prein Carina,
Winkler Thomas,
Kirsch Manuela,
Hopfner Ursula,
Streichert Thomas,
ClausenSchaumann Hauke,
Zustin Jozef,
Kirchhof Kristin,
Morlock Michael M.,
Machens HansGünter,
Schilling Arndt Friedrich
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15227
Subject(s) - osteoid , chemistry , bone resorption , extracellular matrix , resorption , osteomalacia , cellular differentiation , microbiology and biotechnology , mineralization (soil science) , bone sialoprotein , biochemistry , endocrinology , biology , anatomy , osteoporosis , alkaline phosphatase , osteocalcin , organic chemistry , gene , nitrogen , enzyme
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.