The effect of exogenous histone H1 on rat adipose-derived stem cell proliferation, migration, and osteogenic differentiation in vitro.
Adipose-derived stem cells (ASCs) are of great interest for the development of novel cell therapies due to their ease of isolation and expansion, immunosuppressive activity, and multilineage differentiation potential. However, the mechanisms underlying the therapeutic potential of ASCs remain to be elucidated. Others and we have shown that nuclear proteins such as histone H1 and high mobility group box 1 (HMGB1) play important roles in the maturation of dendritic cells (DCs). Furthermore, we previously demonstrated translocation of histone H1 from the nucleus to the cytoplasm and activation of mitogen-activated protein kinases (MAPKs) in DCs. In the present study, we confirmed that histone H1 does not alter the immunophenotype and immunosuppression potential of ASCs, but that histone H1 enhanced wound healing and increased interleukin (IL)-6 expression. Moreover, histone H1 treated-ASCs showed up-regulation of MAPKs extracellular-regulated kinase 1/2 (ERK1/2) and sequential NF-κB translocation. Finally, we found that culture in differentiation media supplemented with histone H1 enhanced ASC osteogenesis. In contrast, inhibition of histone H1 by small interfering RNA (siRNA) reduced osteogenic differentiation markers including ALP. These results suggest that histone H1 may be useful for induction of mesenchymal stem cells in tissue engineering and future potential ASC therapies.
Center for Translational Research in Biomedical Sciences, Liver Transplantation Program and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Niao-Sung, Kaohsiung, Taiwan.
Li-Wen
LW
Hsu
Shigeru
S
Goto
Toshiaki
T
Nakano
Kuang-Den
KD
Chen
Chih-Chi
CC
Wang
Chia-Yun
CY
Lai
Chiung-Hui
CH
Hou
Yen-Chen
YC
Chang
Yu-Fan
YF
Cheng
King-Wah
KW
Chiu
Chien-Chih
CC
Chen
Shu-Hui
SH
Chen
Chao-Long
CL
Chen
D017667:Adipocytes / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D048708:Cell Growth Processes / Q000502:physiology; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism / Q000502:physiology; D024243:HMGB1 Protein / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology*; D021381:Protein Transport; D051381:Rats; D011917:Rats, Inbred Lew; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology*; D023822:Tissue Engineering / Q000379:methods; D015854:Up-Regulation; D014945:Wound Healing / Q000235:genetics / Q000502:physiology
D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D006657:Histones; D015850:Interleukin-6; D016328:NF-kappa B; D020928:Mitogen-Activated Protein Kinases