PMID- 19769530
OWN - NLM
STAT- MEDLINE
DCOM- 20100927
LR  - 20220410
IS  - 1937-335X (Electronic)
IS  - 1937-3341 (Linking)
VI  - 16
IP  - 2
DP  - 2010 Feb
TI  - Transforming growth factor beta1 induces osteogenic differentiation of murine 
      bone marrow stromal cells.
PG  - 725-33
LID - 10.1089/ten.TEA.2009.0495 [doi]
AB  - Bone marrow stromal cells (BMSCs) have been shown to contribute to regeneration 
      of numerous mesodermal tissue types including adipose, bone, and cartilage. 
      Recent studies have shown that BMSCs migrate into damaged bone and help 
      facilitate effects such as fracture healing. Although bone morphogenic proteins 
      have been shown to stimulate bone repair, their levels remain low postfracture. 
      Peripheral blood levels of transforming growth factor beta1 (TGF-beta1), on the 
      other hand, rise dramatically within 2 weeks postfracture. Therefore, we 
      investigated the role of TGF-beta1 on BMSC osteogenic differentiation in vitro. 
      Murine BMSCs were freshly isolated from femurs, fluorescence-activated cell 
      sorted for Sca-1, cultured in Iscove's modified Dulbecco's medium, and exposed to 
      TGF-beta1. After 14 days, real-time reverse transcriptase-polymerase chain 
      reaction and immunohistochemical staining were performed to examine the 
      expression of self-renewal and terminal differentiation markers. Results showed 
      that the treatment with TGF-beta1 reduced mRNA levels of self-renewal markers 
      (Oct4, Stella, Nanos3, and Abcg2) by twofold and increased osteoblast 
      differentiation markers (Runx2, Opn, and Col1) up to sevenfold compared with 
      controls. We also observed decreased mRNA levels of adipogenic markers (Pparg2 
      and Adn) and an increase in alkaline phosphatase activity. Transcriptional 
      coactivator with PDZ-binding motif (TAZ) mRNA and protein levels were elevated up 
      to threefold following TGF-beta1 stimulation. In conclusion, our findings 
      revealed an unexpected osteogenic differentiation pathway in murine BMSCs under 
      the control of TGF-beta that is mediated by TAZ, which is known to increase 
      RUNX2-dependent gene transcription while repressing PPARgamma2-dependent 
      transcription. This is the first report demonstrating the upregulation of TAZ 
      activity in BMSCs by a physiological growth factor present during acute bone 
      injury.
FAU - Zhao, Longmei
AU  - Zhao L
AD  - Division of Plastic Surgery, Department of Surgery, Stanford University School of 
      Medicine, Stanford, California 94305, USA.
FAU - Jiang, Shu
AU  - Jiang S
FAU - Hantash, Basil M
AU  - Hantash BM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Tissue Eng Part A
JT  - Tissue engineering. Part A
JID - 101466659
RN  - 0 (RNA, Messenger)
RN  - 0 (Smad Proteins)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - EC 3.1.3.1 (Alkaline Phosphatase)
SB  - IM
MH  - Adipogenesis/drug effects
MH  - Alkaline Phosphatase/metabolism
MH  - Animals
MH  - Bone Marrow Cells/*cytology/*drug effects/enzymology
MH  - Cell Differentiation/drug effects/*genetics
MH  - Cell Lineage/drug effects
MH  - Cell Separation
MH  - Epidermal Growth Factor/pharmacology
MH  - Female
MH  - Fibroblasts/cytology/drug effects
MH  - Gene Expression Regulation/drug effects
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Osteogenesis/*drug effects/genetics
MH  - RNA, Messenger/genetics/metabolism
MH  - Smad Proteins/genetics/metabolism
MH  - Stromal Cells/cytology/drug effects/enzymology
MH  - Transforming Growth Factor beta1/*pharmacology
EDAT- 2009/09/23 06:00
MHDA- 2010/09/29 06:00
CRDT- 2009/09/23 06:00
PHST- 2009/09/23 06:00 [entrez]
PHST- 2009/09/23 06:00 [pubmed]
PHST- 2010/09/29 06:00 [medline]
AID - 10.1089/ten.TEA.2009.0495 [doi]
PST - ppublish
SO  - Tissue Eng Part A. 2010 Feb;16(2):725-33. doi: 10.1089/ten.TEA.2009.0495.