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Bone Abstracts (2014) 3 PP151 | DOI: 10.1530/boneabs.3.PP151

ECTS2014 Poster Presentations Cell biology: osteoblasts and bone formation (48 abstracts)

Syndecan-2 is a new negative modulator of Wnt signaling within bone marrow

Rafik Mansouri 1, , Valérie Geoffroy 1, , Pierre Marie 1, & Dominique Modrowski 1,

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1INSERM U1132, Paris, France; 2Université Paris Diderot-Paris 7, Paris, France.


Wnt factors bind to heparan sulfate chains of syndecans that hence control their distribution in the cell microenvironment and also contribute to the internalization and recycling of the Wnt receptors. Syndecans are therefore likely important Wnt regulators within the bone marrow. Here, we investigated the interactions between Syndecan-2 and Wnt signaling in normal bone cells. We analyzed the effects of 2.3 kb Col1A1 promoter-driven Syndecan-2 overexpression in osteoblasts. Syndecan-2 overexpression resulted in decreased Wnt/beta-catenin signaling in TG mice bearing a Wnt reporter system. Syndecan-2 overexpressing bone cells displayed lower Wnt expression and also a weaker response to recombinant Wnt. Altered levels of Wnt receptors, effectors and inhibitors were found in bone marrow cells of TG mice. Specially, R-spondins expression was decreased in bone marrow cells of transgenic mice. Indeed, Wnt3a stimulation induced a strong increase in the levels of R-spondin-2 in the cytoplasm of bone marrow cells derived from WT mouse bone and at the opposite, Wnt3a decreased R-spondin-2 in cells from TG mice. Wnt3a treatment resulted in R-spondin-2 ubiquitination in Syndecan-2 overexpression cells, suggesting that the proteoglycan was involved in Wnt signaling system internalization and degradation. Adult TG mice displayed decreased bone mass, reduced number of active osteoclasts and osteoblasts. The osteoclast alteration was clearly related to a defect in the stromal cell population. TUNEL staining revealed an increased number of apoptotic cells within the bone marrow of TG as compared to WT mice. In cultures of bone-derived cells, syndecan-2 appearance matched with cell death induction. Moreover, syndecan-2 overexpressing osteoblasts were shown to induce apoptosis of co-cultured bone marrow cells derived from WT mice. Altogether our results revealed a new role of Syndecan-2 in the microenvironment of bone marrow cells. Syndecan-2 appeared as a key regulator of Wnt signaling and thereby of the fate of precursor cells.

Volume 3

European Calcified Tissue Society Congress 2014

Prague, Czech Republic
17 May 2014 - 20 May 2014

European Calcified Tissue Society 

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