Osteogenic and chondrogenic differentiation of embryonic stem cells in response to specific growth factors

• Published in: Bone (New York, N.Y.) Vol. 36; no. 5; pp. 758 - 769
• Main Authors: Kawaguchi, Jitsutaro, Mee, Patrick J., Smith, Austin G.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.05.2005; Elsevier Science
• Subjects: Alkaline Phosphatase - biosynthesis; Animals; Base Sequence; Biological and medical sciences; Biomarkers; Bone morphogenetic protein; Bone Morphogenetic Protein 4; Bone Morphogenetic Proteins - physiology; Cell Differentiation - drug effects; Cell differentiation, maturation, development, hematopoiesis; Cell Lineage; Cell physiology; Chondrocyte; Chondrocytes - cytology; Culture Media; DNA Primers; Embryo, Mammalian - cytology; Embryonic stem cell; Enzyme Induction; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Developmental - physiology; Mice; Molecular and cellular biology; Osteoblast; Osteoblasts - cytology; Reverse Transcriptase Polymerase Chain Reaction; Stem Cells - cytology; Transforming growth factor-β; Embryonic stem cell; Osteoblast; Bone morphogenetic protein; Chondrocyte; Transforming growth factor-β; Cell proliferation; Transforming growth factor β; Stem cell; Cell differentiation; Growth factor
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/j.bone.2004.07.019

Reliable in vitro conversion of pluripotent embryonic stem (ES) cells into bone and cartilage-forming cells would expand opportunities for experimental investigations of skeletogenesis and could also provide new cellular sources for pharmaceutical screening and for cell therapy applications. Here, we evaluate the generation of mesenchymal cell lineages from mouse ES cells following treatment of embryoid bodies with retinoic acid, previously reported to induce development of adipocyte precursors. We find that retinoic acid reduces mesodermal differentiation but enhances expression of markers of neural crest, an alternative origin of mesenchymal elements. Runx1 and Ptprv appear to provide early markers of mesenchymal potential. Subsequently, different mesenchymal fates are generated in response to particular growth factors. Substitution of the adipogenic factors insulin and triiodothyronine with bone morphogenetic protein (BMP-4) results in suppression of adipogenesis and development of a mature osteogenic phenotype. In contrast, treatment with transforming growth factor-β (TGF-β 3) promotes chondrogenic differentiation. Thus, the use of appropriate growth factors and culture milieu steers differentiation of ES cell-derived precursors into distinct mesenchymal compartments.