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


METHODS
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 factor-beta 1 (TGF-beta(1)) as a positive control in vitro for 3 weeks. The effects on cartilaginous differentiation and proliferation were assayed.


RESULTS
MSCs when treated with either Shh or TGF-beta(1) showed expression of cartilage markers aggrecan, Sox9, CEP-68, and collagen type II and X within 3 weeks. Only r-Shh-treated cells showed a very strong cell proliferation and much higher BrdU incorporation in cell assay systems.


CONCLUSIONS
These are the first data that indicate an important role of Shh for the induction of cartilage production by MSCs in vitro.
Warzecha
Jörg
J
Department of Orthopaedic Surgery, Johann Wolfgang Goethe-University Hospital, Marienburgstrasse 2, Frankfurt am Main, 60528, Germany.
Göttig
Stephan
S
Brüning
Christian
C
Lindhorst
Elmar
E
Arabmothlagh
Mohammad
M
Kurth
Andreas
A
D000328:Adult; D053674:Aggrecans / Q000235:genetics / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002356:Cartilage / Q000166:cytology*; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D024121:Collagen Type X / Q000235:genetics / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D053823:Hedgehog Proteins / Q000494:pharmacology*; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D008875:Middle Aged; D012313:RNA / Q000235:genetics; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055758:SOX9 Transcription Factor; D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
D053674:Aggrecans; C422245:CRTAC1 protein, human; D002135:Calcium-Binding Proteins; D024043:Collagen Type II; D024121:Collagen Type X; D053823:Hedgehog Proteins; D006609:High Mobility Group Proteins; D011994:Recombinant Proteins; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D012313:RNA