Osteoblasts Directly Control Lineage Commitment of Mesenchymal Progenitor Cells through Wnt Signaling

• Published in: The Journal of biological chemistry 2008-01, Vol.283 (4), p.1936-1945
• Main Authors: Zhou, Hong, Mak, Wendy, Zheng, Yu, Dunstan, Colin R., Seibel, Markus J.
• Format: Article
• Language: English
• Subjects: Adipogenesis - drug effects; Adipogenesis - physiology; Animals; beta Catenin - biosynthesis; beta Catenin - genetics; Cell Differentiation - drug effects; Cell Differentiation - physiology; Cell Line; Fusion Regulatory Protein-1 - pharmacology; Glycoproteins - biosynthesis; Glycoproteins - genetics; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Mice; Mice, Transgenic; Osteoblasts - cytology; Osteoblasts - metabolism; Proto-Oncogene Proteins - biosynthesis; Proto-Oncogene Proteins - genetics; Signal Transduction - drug effects; Signal Transduction - physiology; Wnt Proteins - biosynthesis; Wnt Proteins - genetics; Wnt3 Protein; Wnt3A Protein
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M702687200

Lineage commitment of mesenchymal progenitor cells is still poorly understood. Here we demonstrate that Wnt signaling by osteoblasts is essential for mesenchymal progenitor cells to differentiate away from a default adipogenic into an osteoblastic lineage. Dominant adipogenesis and reduced osteoblastogenesis were observed in calvarial cell cultures from transgenic mice characterized by osteoblast-targeted disruption of glucocorticoid signaling. This phenotypic shift in mesenchymal progenitor cell commitment was associated with reciprocal regulation of early adipogenic and osteoblastogenic transcription factors and with a reduction in Wnt7b and Wnt10b mRNA and β-catenin protein levels in transgenic versus non-transgenic cultures. Transwell co-culture of transgenic mesenchymal progenitor cells with wild type osteoblasts restored commitment to the osteoblast lineage. This effect was blocked by adding sFRP1, a Wnt inhibitor, to the co-culture. Treatment of transgenic cultures with Wnt3a resulted in stimulation of osteoblastogenesis and suppression of adipogenesis. Our findings suggest a novel cellular mechanism in bone cell biology in which osteoblasts exert direct control over the lineage commitment of their mesenchymal progenitor through Wnt signaling. This glucocorticoid-dependent forward control function indicates a central role for osteoblasts in the regulation of early osteoblastogenesis.