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Osteoporosis is accompanied by reduced CD274 expression in human bone marrow-derived mesenchymal stem cells
1Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.zeller.alexander@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.
Insights
Human bone marrow-derived mesenchymal stem cells (hBMSCs) from osteoporotic donors exhibit lower CD274 expression. This finding suggests CD274 may influence bone metabolism and offers potential for novel osteoporosis therapies.
Area of Science:
- Stem cell biology
- Orthopedics
- Immunology
Background:
- Osteoporosis pathogenesis remains incompletely understood.
- Cell-based therapies offer potential for treating osteoporosis.
- Investigating differences in mesenchymal stem cells (MSCs) between healthy and osteoporotic individuals is crucial.
Purpose of the Study:
- To compare human bone marrow-derived mesenchymal stem cells (hBMSCs) from healthy donors and osteoporotic patients.
- To analyze differences in differentiation potential, proliferation, surface antigen expression, and gene expression.
- To identify potential therapeutic targets for osteoporosis.
Main Methods:
- Retrospective analysis of hBMSCs from seven healthy and seven osteoporotic donors.
- Flow cytometry to assess cell surface antigen expression (specifically CD274).
- RT2 Osteoporosis Profiler PCR array and quantitative real-time PCR for gene expression analysis.
Main Results:
- hBMSCs from osteoporotic donors showed significantly lower CD274 expression compared to controls (4.98% vs. 26.03%, p=0.007).
- Genes inhibiting the WNT signaling pathway and stimulating bone resorption were upregulated in osteoporotic hBMSCs.
- No significant differences were observed in differentiation potential, proliferation, or other surface antigens.
Conclusions:
- CD274 expression is significantly reduced in hBMSCs from osteoporotic patients.
- CD274 may play a role in regulating bone metabolism.
- CD274 represents a potential target for future osteoporosis research and cell-based therapies.
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