The high mobility group transcription factor Sox8 is a negative regulator of osteoblast differentiation.
Bone remodeling is an important physiologic process that is required to maintain a constant bone mass. This is achieved through a balanced activity of bone-resorbing osteoclasts and bone-forming osteoblasts. In this study, we identify the high mobility group transcription factor Sox8 as a physiologic regulator of bone formation. Sox8-deficient mice display a low bone mass phenotype that is caused by a precocious osteoblast differentiation. Accordingly, primary osteoblasts derived from these mice show an accelerated mineralization ex vivo and a premature expression of osteoblast differentiation markers. To confirm the function of Sox8 as a negative regulator of osteoblast differentiation we generated transgenic mice that express Sox8 under the control of an osteoblast-specific Col1a1 promoter fragment. These mice display a severely impaired bone formation that can be explained by a strongly reduced expression of runt-related transcription factor 2, a gene encoding a transcription factor required for osteoblast differentiation. Together, these data demonstrate a novel function of Sox8, whose tightly controlled expression is critical for bone formation.
Schmidt
Katy
K
Institute of Biochemistry, Friedrich-Alexander-University, Erlangen-Nürnberg, Erlangen 91054, Germany.
Schinke
Thorsten
T
Haberland
Michael
M
Priemel
Matthias
M
Schilling
Arndt F
AF
Mueldner
Cordula
C
Rueger
Johannes M
JM
Sock
Elisabeth
E
Wegner
Michael
M
Amling
Michael
M
D000818:Animals; D000831:Animals, Newborn; D001851:Bone Diseases, Metabolic / Q000235:genetics; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000378:metabolism; D002113:Calcification, Physiologic; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D018507:Gene Expression Regulation, Developmental; D006609:High Mobility Group Proteins / Q000172:deficiency*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000166:cytology*; D011401:Promoter Regions, Genetic; D011859:Radiography; D055757:SOXE Transcription Factors; D013194:Staining and Labeling; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism / Q000502:physiology
D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D055757:SOXE Transcription Factors; C498639:Sox8 protein, mouse; D050656:Transcription Factor AP-2; D014157:Transcription Factors