Abstract:
:Bone abnormalities as a consequence of osteoblast deregulation are associated with several diseases such as diabetes and chronic kidney disease. Important role for oxidized low density lipoproteins (oxLDL) in the pathophysiology of bone disorders has been reported. However, little is known about the effects and mechanisms of oxLDL on the process of osteoblastogenesis in human mesenchymal stem cells (MSCs). We show that oxLDL concentrations of ~ 10-25 µg protein (0.43-1.0 µM MDA/mg protein) inhibited the differentiation of MSCs to osteoblasts. We demonstrate that the underlying mechanism entails the suppression of the Wnt signaling through the down-regulation of β-catenin. Further, we show the association of scavenger receptor CD36 with the receptors LRP5/6 and Frizzled in mediating the oxLDL effects on the differentiation of MSCs to pre-osteoblasts. Inhibiting CD36 restored osteoblasts differentiation in the presence of oxLDL. Our findings suggest that oxLDL interferes with the canonical Wnt signaling pathway in a CD36 dependent manner leading to an inhibition of osteoblastogenesis.
journal_name
Mol Biol Repjournal_title
Molecular biology reportsauthors
Dawodu D,Patecki M,Dumler I,Haller H,Kiyan Ydoi
10.1007/s11033-019-04735-5subject
Has Abstractpub_date
2019-06-01 00:00:00pages
3487-3496issue
3eissn
0301-4851issn
1573-4978pii
10.1007/s11033-019-04735-5journal_volume
46pub_type
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