Research Article Wnt signalling mediates the cross-talk between bone marrow derived pre-adipocytic and pre-osteoblastic cell populations Hanna Taipaleenmäki a, b, 1 , Basem M. Abdallah a, ⁎ , 1 , Abdullah AlDahmash c , Anna-Marja Säämänen b , Moustapha Kassem a, c a Department of Endocrinology and Metabolism, Endocrine Research Laboratory (KMEB), Odense University Hospital, Odense, Denmark b Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland c Stem Cell Unit, King Saud University, Riyadh, Saudi Arabia ARTICLE INFORMATION ABSTRACT Article Chronology: Received 14 June 2010 Revised version received 18 November 2010 Accepted 17 December 2010 Available online 4 January 2011 The mechanisms underlying the inverse relationship between osteogenic and adipogenic differentiation of bone marrow stromal cells (MSC) are not known in detail. We have previously established two cell lines from mouse bone marrow that are committed to either osteogenic (osteoblasts and chondrocytes) (mMSC Bone ) or adipogenic (mMSC Adipo ) lineage. To identify the molecular mechanism determining the lineage commitment, we compared the basal gene expression profile of mMSC Bone versus mMSC Adipo using Affymetrix GeneChip® MG430A 2.0 Array. Gene annotation analysis based on biological function revealed an over-representation of skeletal development genes in mMSC Bone while genes related to lipid metabolism and immune response were highly expressed in mMSC Adipo . In addition, there was a significant up-regulation of canonical Wnt signalling genes in mMSC Bone compared to mMSC Adipo (p <0.006). Dual-luciferase assay and expression analysis of genes related to Wnt signalling demonstrated significant activation of Wnt signalling pathway in mMSC Bone compared to mMSC Adipo . Reduced Wnt activity in mMSC Adipo was associated with increased expression of the Wnt inhibitor, secreted frizzled-related protein 1 (sFRP-1) at both mRNA and protein levels in mMSC Adipo . Interestingly, conditioned medium (CM) collected from mMSC Adipo (mMSC-CM Adipo ) inhibited osteoblast differentiation of mMSC, while depletion of sFRP-1 protein from mMSC-CM Adipo abolished its inhibitory effect on osteoblast differentiation. Furthermore, treatment of mMSC with recombinant sFRP-1 resulted in a dose- dependent inhibition of osteoblast and stimulation of adipocyte differentiation. In conclusion, cross- talk exists between different populations of MSC in the bone marrow, and Wnt signalling functions as a molecular switch that determines the balance between osteoblastogenesis and adipogenesis. © 2010 Elsevier Inc. All rights reserved. Keywords: Mesenchymal stromal cell Adipocyte Osteoblast Wnt signaling sFRP-1 Introduction Osteogenesis and adipogenesis are strongly associated processes [1]. Several in vivo studies have revealed that in bone loss states, e.g. aging, osteoporosis and glucocorticoid therapy, there is an inhibition of bone formation and increased bone marrow adipo- genesis [2–6]. Bone and fat formation in the bone marrow are thought to be mediated by osteoblastic and adipocytic cells that EXPERIMENTAL CELL RESEARCH 317 (2011) 745 – 756 ⁎ Corresponding author. Molecular Endocrinology Laboratory (KMEB), Odense University Hospital SDU, DK-5000 Odense C, Denmark. Fax: +45 65503950. E-mail address: babdallah@health.sdu.dk (B.M. Abdallah). 1 These authors equally contributed to the work. 0014-4827/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.yexcr.2010.12.015 available at www.sciencedirect.com www.elsevier.com/locate/yexcr