Title: Osteoporosis is accompanied by reduced CD274 expression in human bone marrow-derived mesenchymal stem cells

Authors: A-N Zeller, M Selle, Z Gong, M Winkelmann, C Krettek, K Bundkirchen, C Neunaber, S Noack

Address: Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany

E-mail: zeller.alexander at mh-hannover.de

Abstract: Underlying pathomechanisms of osteoporosis are still not fully elucidated. Cell-based therapy approaches pose new possibilities to treat osteoporosis and its complications. The aim of this study was to quantify differences in human bone marrow-derived mesenchymal stem cells (hBMSCs) between healthy donors and those suffering from clinically manifest osteoporosis.
Cell samples of seven donors for each group were selected retrospectively from the hBMSC cell bank of the Trauma Department of Hannover Medical School. Cells were evaluated for their adipogenic, osteogenic and chondrogenic differentiation potential, for their proliferation potential and expression of surface antigens. Furthermore, a RT2 Osteoporosis Profiler PCR array, as well as quantitative real-time PCR were carried out to evaluate changes in gene expression.
Cultivated hBMSCs from osteoporotic donors showed significantly lower cell surface expression of CD274 (4.98 % ± 2.38 %) than those from the control group (26.03 % ± 13.39 %; p = 0.007), as assessed by flow cytometry. In osteoporotic patients, genes involved in inhibition of the anabolic WNT signalling pathway and those associated with stimulation of bone resorption were significantly upregulated. Apart from these changes, no significant differences were found for the other cell surface antigens, adipogenic, osteogenic and chondrogenic differentiation ability as well as proliferation potential.
These findings supported the theory of an influence of CD274 on the regulation of bone metabolism. CD274 might be a promising target for further investigations of the pathogenesis of osteoporosis and of cell-based therapies involving MSCs.

Key Words: Osteoporosis, mesenchymal stem cells, CD274, osteoblasts, gene expression.

Publication date: May 31st 2021

Article download: Pages 603-615 (PDF file)
DOI: 10.22203/eCM.v041a39