Retinoic acid disrupts osteogenesis in pre-osteoblasts by down-regulating WNT signaling.
Publication year
2019Source
International Journal of Biochemistry & Cell Biology, 116, (2019), pp. 105597ISSN
Annotation
01 november 2019
Publication type
Article / Letter to editor

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Organization
Dentistry
Journal title
International Journal of Biochemistry & Cell Biology
Volume
vol. 116
Page start
p. 105597
Subject
Radboudumc 10: Reconstructive and regenerative medicine RIMLS: Radboud Institute for Molecular Life SciencesAbstract
The skull bones are formed by osteoblasts by intramembranous ossification. WNT signaling is a regulator of bone formation. Retinoic Acid (RA) act as a teratogen affecting craniofacial development. We evaluated the effects of RA on the differentiation and mineralization of MC-3T3 cells, and on the expression of WNT components. MC-3T3 were cultured with or without 0.5 muM RA in osteogenic medium and mineralization was assessed by alizarin red staining. The expression of osteogenic marker genes and WNT genes was evaluated at several time points up to 28 days. RA significantly inhibited MC-3T3mineralization (p<0.01), without affecting ALP activity or Alp gene expression. Both parameters gradually increased in time. During culture, RA stimulated Runx2 expression at 14 and 28 days compared to the respective controls (p<0.05). Also, RA significantly reduced Sp7 expression at days 14 and 21 (p<0.05). Simultaneously, RA significantly reduced the expression of the WNT genes cMyc, Lef1, Lrp5, Lrp6 and Wnt11 compared to the controls (p<0.05). In contrast, RA increased the expression of the WNT inhibitors Dkk1 at day 21 and Dkk2 at days 14 and 21 (p<0.01). Our data indicate that RA disrupts osteogenic differentiation and mineralization by inhibiting WNT signaling.
This item appears in the following Collection(s)
- Academic publications [227881]
- Electronic publications [107344]
- Faculty of Medical Sciences [86219]
- Open Access publications [76470]
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