oxLDL inhibits differentiation of mesenchymal stem cells into osteoblasts via the CD36 mediated suppression of Wnt signaling pathway
- 179 Downloads
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.
KeywordsOxLDL Mesenchymal stem cells (MSCs) Osteoblast differentiation Wnt signaling CD36
We are grateful to Frank Hausadel and Birgit Habermeyer for excellent technical assistance. The work was supported by the Grant from Elsbeth Bonhoff Stiftung (Berlin, Germany).
- 5.Marcellini S, Henriquez JP, Bertin A (2012) Control of osteogenesis by the canonical Wnt and BMP pathways in vivo: cooperation and antagonism between the canonical Wnt and BMP pathways as cells differentiate from osteochondroprogenitors to osteoblasts and osteocytes. BioEssays 34:953–962CrossRefGoogle Scholar
- 9.Moderate B (2009) 1: Diagnosis of CKD-MBD: biochemical abnormalities. Kidney Int 76113:S22–S49Google Scholar
- 13.Baldini V, Mastropasqua M, Francucci CM, D’Erasmo E (2005) Cardiovascular disease and osteoporosis. J Endocrinol Invest 28:69–72Google Scholar
- 28.Xin Ye PY, Zhang J, Sun Q, Ge S, Zhang Xu (2016) Oxidized phospholipids inhibit cnaonical Wnt signaling and ostoeblast differentation via ERK activation. Int J Clin Exp Pathol 9:7941–7950Google Scholar