Searchable abstracts of presentations at key conferences on calcified tissues
Bone Abstracts (2013) 1 PP180 | DOI: 10.1530/boneabs.1.PP180

ECTS2013 Poster Presentations Cell biology: osteoblasts and bone formation (50 abstracts)

N-cadherin governs age-related osteoprogenitor cell determination in mice through modulation of Wnt5a and Wnt10b

Eric Haÿ , François-Xavier Dieudonné , Caroline Marty & Pierre J Marie

INSERM U606, and University Paris Diderot, Sorbonne Paris Cité, Paris, France.

Senile osteoporosis and age-related osteopenia are associated with decreased osteoblastogenesis and increased bone marrow adipogenesis. The mechanisms controlling the fate determination of osteoblast to adipocyte differentiation of bone marrow stromal cells (BMSC) during aging are not known. We and others previously showed that the cell-cell adhesion molecule N-cadherin (N-Cadh) expressed in osteoblasts controls bone formation, but little is known about its role in BMSC fate determination. Here, we tested the hypothesis that N-Cadh governs BMSC fate during skeletal aging in mice. We found that N-Cadh overexpression in osteoblasts leads to increased BMSC adipogenic differentiation and increased bone marrow fat associated with decreased BMSC osteoblast differentiation and bone formation in young (1.5 months) transgenic (Tg) mice, whereas in aging (18 months) N-Cadh Tg mice, BMSC adipogenic differentiation was reduced while osteogenic differentiation was increased, which resulted in increased bone formation and bone mass. This change in BMSC determination was associated with an age-related decrease in endogenous N-Cadh expression associated with increased Wnt5a, Wnt10b expression in bone. Conditioned media from old N-Cadh Tg osteoblasts which express high Wnt5a and Wnt10b restored osteoblast differentiation in young N-Cadh Tg osteoblasts, and this effect was abrogated by Wnt5a and Wnt10b silencing, demonstrating that the age-related BMSC fate is controlled by N-Cadh-mediated changes in Wnt5a and Wnt10b. Transplantation of BMSC derived from old N-Cadh Tg mice into young recipient Tg mice resulted in increased bone volume compared to wild type BMSC, demonstrating the intrinsic role of N-Cadh in the control of bone mass. These data support a model by which N-cadherin-mediated modulation of Wnt5a and Wnt10b in the bone marrow governs the age-related switch in osteoblast to adipocyte differentiation of mesenchymal cells, which in turn regulates bone formation and bone mass during aging.

Volume 1

European Calcified Tissue Society Congress 2013

Lisbon, Portugal
18 May 2013 - 22 May 2013

European Calcified Tissue Society 

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