Tension-induced reduction in connexin 43 expression in cranial sutures is linked to transcriptional regulation by TBX2.
Cranial sutures produce bone at precisely the right rate and time to maintain homeostasis. Connexin 43 (CX43), a protein important for communication in bone, is downregulated during cell proliferation and is released from suppression or upregulated during differentiation. Our previous studies have shown that binding sites for the transcription regulatory protein TBX2 are located in the promoter sequence, upstream of the Cx43 gene. We have shown that TBX2 binding suppresses Cx43 expression. The current study uses transgenic mice in which the TBX2 promoter has been spliced upstream of the coding sequence for green fluorescent protein (GFP). This study shows upregulation of TBX2 after stretching. RNA from stretched and unstretched sutures was used for GeneChip and Western analysis. The results show an increase in Tbx2 and a decrease in Cx43 gene and protein expression with stretch. Our findings support a model of strain-regulated bone formation with feedback inhibition that maintains sutural patency during development.
Borke
James L
JL
Department of Oral Biology and Maxillofacial Pathology, Medical College of Georgia, and the Veterans Administration Medical Center, Augusta, GA 30912-1129, USA. jborke@mail.mcg.edu
Yu
Jack C
JC
Isales
Carlos M
CM
Wagle
Namita
N
Do
Nha Nam
NN
Chen
Jung-Ren
JR
Bollag
Roni J
RJ
D000818:Animals; D015153:Blotting, Western; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D003393:Cranial Sutures / Q000378:metabolism / Q000502:physiology*; D015536:Down-Regulation; D005786:Gene Expression Regulation; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D010012:Osteogenesis; D051381:Rats; D013314:Stress, Mechanical; D020825:T-Box Domain Proteins / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation
D018031:Connexin 43; C097348:T-Box Domain Protein 2; D020825:T-Box Domain Proteins