N‐Cadherin/Wnt Interaction Controls Bone Marrow Mesenchymal Cell Fate and Bone Mass During Aging. Issue 11 (November 2014)

• Record Type: Journal Article
• Authors: Haÿ, Eric; Dieudonné, François‐Xavier; Saidak, Zuzana; Marty, Caroline; Brun, Julia; Da Nascimento, Sophie; Sonnet, Pascal; Marie, Pierre J.
• Is Part Of: Journal of cellular physiology. Volume 229:Issue 11(2014:Nov.)
• Page Start: 1765
• Page End: 1775
• Publication Date: 2014-11
• Subjects: Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.24629
• Languages: English
• ISSNs: 0021-9541

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="jcp24629-sec-0001" sec-type="section"> <p>Age‐related bone loss is characterized by reduced osteoblastogenesis and excessive bone marrow adipogenesis. The mechanisms governing bone marrow mesenchymal stromal cell (BMSC) differentiation into adipocytes or osteoblasts during aging are unknown. We show here that overexpressing N‐cadherin (<italic>Cadh2</italic>) in osteoblasts increased BMSC adipocyte differentiation and reduced osteoblast differentiation in young transgenic (Tg) mice whereas this phenotype was fully reversed with aging. The reversed phenotype with age was associated with enhanced <italic>Wnt5a</italic> and <italic>Wnt10b</italic> expression in osteoblasts and a concomitant increase in BMSC osteogenic differentiation. Consistent with this mechanism, conditioned media from young wild type osteoblasts inhibited adipogenesis and promoted osteoblast differentiation in BMSC from old <italic>Cadh2</italic> Tg mice, and this response was abolished by <italic>Wnt5a</italic> and <italic>Wnt10b</italic> silencing. Transplantation of BMSC from old <italic>Cadh2</italic> Tg mice into young Tg recipients increased <italic>Wnt5a</italic> and <italic>Wnt10b</italic> expression and rescued BMSC osteogenic differentiation. In senescent osteopenic mice, blocking the CADH2–Wnt interaction using an antagonist peptide increased <italic>Wnt5a</italic> and <italic>Wnt10b</italic> expression, bone formation, and bone mass. The data indicate that Cadh2/Wnt interaction in osteoblasts regulates BMSC lineage determination, bone formation, and bone mass and suggest a therapeutic target for promoting bone formation in the aging skeleton. J. Cell. Physiol. 229: 1765–1775, 2014. © 2014 Wiley Periodicals, Inc.</p> </sec> </abstract>