Role of Slug transcription factor in human mesenchymal stem cells
Elena Torreggiani
Dipartimento di Biochimica e Biologia Molecolare, Sezione di Biologia Molecolare, Università degli Studi di Ferrara, Ferrara, Italy
Search for more papers by this authorGina Lisignoli
Struttura Complessa Laboratorio di Immunoreumatologia e Rigenerazione Tissutale, Istituto Ortopedico Rizzoli, Bologna, Italy
Laboratorio RAMSES, Bologna, Italy
Search for more papers by this authorCristina Manferdini
Struttura Complessa Laboratorio di Immunoreumatologia e Rigenerazione Tissutale, Istituto Ortopedico Rizzoli, Bologna, Italy
Laboratorio RAMSES, Bologna, Italy
Search for more papers by this authorElisabetta Lambertini
Dipartimento di Biochimica e Biologia Molecolare, Sezione di Biologia Molecolare, Università degli Studi di Ferrara, Ferrara, Italy
Search for more papers by this authorLetizia Penolazzi
Dipartimento di Biochimica e Biologia Molecolare, Sezione di Biologia Molecolare, Università degli Studi di Ferrara, Ferrara, Italy
Search for more papers by this authorRenata Vecchiatini
Dipartimento di Biochimica e Biologia Molecolare, Sezione di Biologia Molecolare, Università degli Studi di Ferrara, Ferrara, Italy
Search for more papers by this authorElena Gabusi
Struttura Complessa Laboratorio di Immunoreumatologia e Rigenerazione Tissutale, Istituto Ortopedico Rizzoli, Bologna, Italy
Laboratorio RAMSES, Bologna, Italy
Search for more papers by this authorPasquale Chieco
Center for Applied Biomedical Research, S. Orsola-Malpighi University Hospital, Bologna, Italy
Search for more papers by this authorAndrea Facchini
Struttura Complessa Laboratorio di Immunoreumatologia e Rigenerazione Tissutale, Istituto Ortopedico Rizzoli, Bologna, Italy
Laboratorio RAMSES, Bologna, Italy
Dipartimento di Medicina Clinica, Università degli Studi di Bologna, Bologna, Italy
Search for more papers by this authorRoberto Gambari
Dipartimento di Biochimica e Biologia Molecolare, Sezione di Biologia Molecolare, Università degli Studi di Ferrara, Ferrara, Italy
Search for more papers by this authorCorresponding Author
Roberta Piva
Dipartimento di Biochimica e Biologia Molecolare, Sezione di Biologia Molecolare, Università degli Studi di Ferrara, Ferrara, Italy
Roberta PIVA, Department of Biochemistry and Molecular Biology, University of Ferrara, Via Fossato di Mortara, 74, 44121 Ferrara, Italy. Tel.: +39-532-974405 Fax: +39-532-974484 E-mail: [email protected]Search for more papers by this authorElena Torreggiani
Dipartimento di Biochimica e Biologia Molecolare, Sezione di Biologia Molecolare, Università degli Studi di Ferrara, Ferrara, Italy
Search for more papers by this authorGina Lisignoli
Struttura Complessa Laboratorio di Immunoreumatologia e Rigenerazione Tissutale, Istituto Ortopedico Rizzoli, Bologna, Italy
Laboratorio RAMSES, Bologna, Italy
Search for more papers by this authorCristina Manferdini
Struttura Complessa Laboratorio di Immunoreumatologia e Rigenerazione Tissutale, Istituto Ortopedico Rizzoli, Bologna, Italy
Laboratorio RAMSES, Bologna, Italy
Search for more papers by this authorElisabetta Lambertini
Dipartimento di Biochimica e Biologia Molecolare, Sezione di Biologia Molecolare, Università degli Studi di Ferrara, Ferrara, Italy
Search for more papers by this authorLetizia Penolazzi
Dipartimento di Biochimica e Biologia Molecolare, Sezione di Biologia Molecolare, Università degli Studi di Ferrara, Ferrara, Italy
Search for more papers by this authorRenata Vecchiatini
Dipartimento di Biochimica e Biologia Molecolare, Sezione di Biologia Molecolare, Università degli Studi di Ferrara, Ferrara, Italy
Search for more papers by this authorElena Gabusi
Struttura Complessa Laboratorio di Immunoreumatologia e Rigenerazione Tissutale, Istituto Ortopedico Rizzoli, Bologna, Italy
Laboratorio RAMSES, Bologna, Italy
Search for more papers by this authorPasquale Chieco
Center for Applied Biomedical Research, S. Orsola-Malpighi University Hospital, Bologna, Italy
Search for more papers by this authorAndrea Facchini
Struttura Complessa Laboratorio di Immunoreumatologia e Rigenerazione Tissutale, Istituto Ortopedico Rizzoli, Bologna, Italy
Laboratorio RAMSES, Bologna, Italy
Dipartimento di Medicina Clinica, Università degli Studi di Bologna, Bologna, Italy
Search for more papers by this authorRoberto Gambari
Dipartimento di Biochimica e Biologia Molecolare, Sezione di Biologia Molecolare, Università degli Studi di Ferrara, Ferrara, Italy
Search for more papers by this authorCorresponding Author
Roberta Piva
Dipartimento di Biochimica e Biologia Molecolare, Sezione di Biologia Molecolare, Università degli Studi di Ferrara, Ferrara, Italy
Roberta PIVA, Department of Biochemistry and Molecular Biology, University of Ferrara, Via Fossato di Mortara, 74, 44121 Ferrara, Italy. Tel.: +39-532-974405 Fax: +39-532-974484 E-mail: [email protected]Search for more papers by this authorAbstract
The pathways that control mesenchymal stem cells (MSCs) differentiation are not well understood, and although some of the involved transcription factors (TFs) have been characterized, the role of others remains unclear. We used human MSCs from tibial plateau (TP) trabecular bone, iliac crest (IC) bone marrow and Wharton’s jelly (WJ) umbilical cord demonstrating a variability in their mineral matrix deposition, and in the expression levels of TFs including Runx2, Sox9, Sox5, Sox6, STAT1 and Slug, all involved in the control of osteochondroprogenitors differentiation program. Because we reasoned that the basal expression level of some TFs with crucial role in the control of MSC fate may be correlated with osteogenic potential, we considered the possibility to affect the hMSCs behaviour by using gene silencing approach without exposing cells to induction media. In this study we found that Slug-silenced cells changed in morphology, decreased in their migration ability, increased Sox9 and Sox5 and decreased Sox6 and STAT1 expression. On the contrary, the effect of Slug depletion on Runx2 was influenced by cell type. Interestingly, we demonstrated a direct in vivo regulatory action of Slug by chromatin immunoprecipitation, showing a specific recruitment of this TF in the promoter of Runx2 and Sox9 genes. As a whole, our findings have important potential implication on bone tissue engineering applications, reinforcing the concept that manipulation of specific TF expression levels may elucidate MSC biology and the molecular mechanisms, which promote osteogenic differentiation.
Supporting Information
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Fig S1 Effect of Slug overexpression on osteogenic differentiation of hWJ-MSCs
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