The bone-related Zn finger transcription factor Osterix promotes proliferation of mesenchymal cells.
Osterix is a bone-related transcription factor that functions genetically downstream of Runx2, which controls both growth and differentiation in osteoblasts. Here we assessed the biological function of Osterix in mesenchymal cells that are not normally committed to the osteogenic lineage. Stably transfected NIH3T3 fibroblasts that express exogenous Osterix were examined for their ability to convert into osteoblastic cells by analyzing gene expression profiles of bone phenotype related markers, as well as by measuring bone nodule formation and cell proliferation. Forced expression of Osterix stimulates osteopontin gene expression but not the expression or activity of other bone-related markers, including collagen type I, alkaline phosphatase, osteocalcin, or osteonectin. Moreover, cells stably expressing Osterix do not induce bone nodule formation. Strikingly, both polyclonal and monoclonal cells expressing Osterix exhibit enhanced proliferation. Collectively, these results indicate that Osterix is insufficient to establish osteogenic lineage commitment, perhaps due to the ability of Osterix to promote cell growth. We propose that regulatory pathways operating upstream of or in parallel with Osterix are required for osteogenic conversion of uncommitted mesenchymal cells.
Kim
Yeon-Ju
YJ
Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea.
Kim
Hyun-Nam
HN
Park
Eui-Kyun
EK
Lee
Byung-Heon
BH
Ryoo
Hyun-Mo
HM
Kim
Shin-Yoon
SY
Kim
In-San
IS
Stein
Janet L
JL
Lian
Jane B
JB
Stein
Gary S
GS
van Wijnen
Andre J
AJ
Choi
Je-Yong
JY
D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D008648:Mesoderm / Q000166:cytology / Q000502:physiology*; D051379:Mice; D041681:NIH 3T3 Cells; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology*; D010012:Osteogenesis / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection / Q000379:methods
D000943:Antigens, Differentiation; D050659:Core Binding Factor Alpha 1 Subunit; C493716:Runx2 protein, mouse; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors