Sonic hedgehog protein promotes proliferation and chondrogenic differentiation of bone marrow-derived mesenchymal stem cells in vitro

• Published in: Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 2006-09, Vol.11 (5), p.491-496
• Main Authors: Warzecha, Jörg, Göttig, Stephan, Brüning, Christian, Lindhorst, Elmar, Arabmothlagh, Mohammad, Kurth, Andreas
• Format: Article
• Language: English
• Subjects: Adult; Aggrecans - genetics; Aggrecans - metabolism; Bone Marrow Cells - cytology; Calcium-Binding Proteins - genetics; Calcium-Binding Proteins - metabolism; Cartilage - cytology; Cell Differentiation - drug effects; Cell Proliferation - drug effects; Cells, Cultured; Chondrocytes - cytology; Chondrocytes - drug effects; Chondrocytes - metabolism; Collagen Type II - genetics; Collagen Type II - metabolism; Collagen Type X - genetics; Collagen Type X - metabolism; Female; Follow-Up Studies; Hedgehog Proteins - pharmacology; High Mobility Group Proteins - genetics; High Mobility Group Proteins - metabolism; Humans; Immunohistochemistry; In Vitro Techniques; Male; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - drug effects; Middle Aged; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA - genetics; Sex-Determining Region Y Protein; SOX9 Transcription Factor; Transcription Factors - genetics; Transcription Factors - metabolism; Transforming Growth Factor beta1 - pharmacology
• ISSN: 0949-2658; 1436-2023
• DOI: 10.1007/s00776-006-1058-1

Sonic hedgehog (Shh) protein is known to be an important signaling protein in early embryonic development. Also, Shh is involved in the induction of early cartilaginous differentiation of mesenchymal cells in the limb and in the spine. The impact of Shh on adult stem cells, human bone marrow-derived mesenchymal stem cells (MSCs), was tested. The MSCs were treated either with recombinant Sonic hedgehog protein (r-Shh) or with transforming growth factorbeta 1 (TGF-β1) as a positive control in vitro for 3weeks. The effects on cartilaginous differentiation and proliferation were assayed. MSCs when treated with either Shh or TGF-β1 showed expression of cartilage markers aggrecan, Sox9, CEP- 68, and collagen type II and X within 3weeks. Only r-Shhtreated cells showed a very strong cell proliferation and much higher BrdU incorporation in cell assay systems. These are the first data that indicate an important role of Shh for the induction of cartilage production by MSCs in vitro.