HIGH-MOBILITY GROUP PROTEIN HMGA 2-DERIVED FRAGMENTS STIMULATE THE PROLIFERATION OF CHONDROCYTES AND ADIPOSE TISSUE-DERIVED STEM CELLS

A Richter et al. HMGA2 fragments stimulate chondrocyte proliferation Abstract In previous research, it was shown that recombinant HMGA2 protein enhances the proliferation of porcine chondrocytes grown in vitro, opening up promising applications of this embryonic architectural transcription factor for tissue engineering, such as in cartilage repair. In this paper, we describe the development and analyses of two synthetic fragments comprising the functional AT-hook motifs of the HMGA2 protein, as well as the nuclear transport domain. They can be synthesised up to large scales, while eliminating some of the problems of recombinant protein production, including unwanted modifi cation or contamination by the expression hosts, or of gene therapy approaches such as uncontrolled viral integration and transgene expression even after therapy. Application of one of these peptides onto porcine hyaline cartilage chondrocytes, grown in in vitro monolayer cell culture, showed a growth-promoting effect similar to that of the wild type HMGA2 protein. Furthermore, it also promoted cell growth of adult adipose tissue derived stem cells. Due to its proliferation inducing function and vast availability, this peptide is thus suitable for further application and investigation in various fi elds such as tissue engineering and stem cell research.

[1]  H. Murua Escobar,et al.  Application of high-mobility-group-A proteins increases the proliferative activity of chondrocytes in vitro. , 2009, Tissue engineering. Part A.

[2]  Isabelle Cleynen,et al.  The HMGA proteins: a myriad of functions (Review). , 2008, International journal of oncology.

[3]  A. Rustighi,et al.  The second AT-hook of the architectural transcription factor HMGA2 is determinant for nuclear localization and function , 2007, Nucleic acids research.

[4]  S. Lowe,et al.  A Novel Role for High-Mobility Group A Proteins in Cellular Senescence and Heterochromatin Formation , 2006, Cell.

[5]  D. Prockop,et al.  Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. , 2006, Cytotherapy.

[6]  H. Lorenz,et al.  Chondrogenic Potential of Multipotential Cells from Human Adipose Tissue , 2004, Plastic and reconstructive surgery.

[7]  Santa Jeremy Ono,et al.  Molecular dissection of the architectural transcription factor HMGA2. , 2003, Biochemistry.

[8]  R. Reeves,et al.  HMGA proteins as therapeutic drug targets. , 2003, Progress in cell cycle research.

[9]  R. Reeves,et al.  HMGI/Y proteins: flexible regulators of transcription and chromatin structure. , 2001, Biochimica et biophysica acta.

[10]  H. Lorenz,et al.  Multilineage cells from human adipose tissue: implications for cell-based therapies. , 2001, Tissue engineering.

[11]  C. Croce,et al.  The expression of a truncated HMGI-C gene induces gigantism associated with lipomatosis. , 1999, Cancer research.

[12]  G. Viglietto,et al.  Truncated and chimeric HMGI-C genes induce neoplastic transformation of NIH3T3 murine fibroblasts , 1998, Oncogene.

[13]  G. Goodwin The high mobility group protein, HMGI-C. , 1998, The international journal of biochemistry & cell biology.

[14]  M. Merika,et al.  Intra- and intermolecular cooperative binding of high-mobility-group protein I(Y) to the beta-interferon promoter , 1997, Molecular and cellular biology.

[15]  P. Rogalla,et al.  HMGI-C expression patterns in human tissues. Implications for the genesis of frequent mesenchymal tumors. , 1996, The American journal of pathology.

[16]  U. Patel,et al.  The gene for the human architectural transcription factor HMGI-C consists of five exons each coding for a distinct functional element. , 1995, Nucleic acids research.

[17]  D. Wemmer,et al.  Short peptide fragments derived from HMG-I/Y proteins bind specifically to the minor groove of DNA. , 1994, Biochemistry.

[18]  M. Nissen,et al.  The A.T-DNA-binding domain of mammalian high mobility group I chromosomal proteins. A novel peptide motif for recognizing DNA structure. , 1990, The Journal of biological chemistry.