Lamin A/C Acts as an Essential Factor in Mesenchymal Stem Cell Differentiation Through the Regulation of the Dynamics of the Wnt/β‐Catenin Pathway. Issue 10 (October 2015)

• Record Type: Journal Article
• Authors: Bermeo, Sandra; Vidal, Christopher; Zhou, Hong; Duque, Gustavo
• Is Part Of: Journal of cellular biochemistry. Volume 116:Issue 10(2015:Oct.)
• Page Start: 2344
• Page End: 2353
• Publication Date: 2015-10
• Subjects: Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.25185
• Languages: English
• ISSNs: 0730-2312

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>ABSTRACT</title> <sec id="jcb25185-sec-0001" sec-type="section"> <p>Changes in the expression of lamin A/C, a fibrilar protein of the nuclear envelope, are associated with the cellular features of age‐related bone loss. Reduced expression of lamin A/C inhibits osteoblastogenesis while facilitating adipogenic differentiation of mesenchymal stem cells (MSC) in vitro and in vivo. In this study we investigated the regulatory role that lamin A/C plays on the essential elements of the Wnt/β‐catenin pathway, which are pivotal in MSC differentiation. Initially, we assessed the effect of lamin A/C gene (<italic>LMNA</italic>) overexpression on MSC differentiation while compared it to lamin A/C depleted MSC. Osteogenesis and gene expression of osteogenic factors were higher in <italic>LMNA</italic>‐transfected MSC as compared to control. Conversely, adipogenesis and expression of adipogenic factors were significantly lower in <italic>LMNA</italic> transfected cells. Nuclear β‐catenin was significantly higher (∼two fold) in MSC expressing higher levels of <italic>LMNA</italic> as compared to control with nuclear β‐catenin levels being significantly lower (∼ ‐42%) in siRNA‐treated MSC. Luciferase activity for β‐catenin‐mediated transcriptional activation was significantly higher in cells overexpressing <italic>LMNA</italic>. These data indicate that MSC overexpressing <italic>LMNA</italic> have higher osteogenic and lower adipogenic differentiation potential. In conclusion, our studies demonstrate that lamin A/C plays a significant role in the differentiation of both osteoblasts and adipocytes by regulating some of the elements of Wnt/β‐catenin signaling during early MSC differentiation. J. Cell. Biochem. 116: 2344–2353, 2015. © 2015 Wiley Periodicals, Inc.</p> </sec> </abstract>