Gene expression changes in cancellous bone of type 2 diabetics: a biomolecular basis for diabetic bone disease.
OBJECTIVE
Diabetes mellitus type 2 (2DM) is associated with altered bone quality. In order to analyze associated changes on a molecular level, we investigated the gene expression of key factors of osteoblast metabolism in type 2 diabetics.


METHODS
Total mRNA and protein of bone samples from 2DM patients and non-diabetic patients were isolated, and subsequently, reverse transcription polymerase chain reaction (RT-PCR) or Western blot was performed. Furthermore, pro- and anti-inflammatory serum cytokine levels were determined using a cytokine array.


RESULTS
Expression of runt-related transcription factor 2 (RUNX2) was increased by 53 %. Expression of the bone sialoproteins, secreted phosphoprotein 1 (SPP1; osteopontin), and integrin-binding sialoprotein (IBSP), was elevated by more than 50 %, and activating transcription factor 4 (ATF4) expression was 13 % lower in the investigated diabetes group compared to the control group. Similarly, the expression of versican (VCAN) and decorin (DCN) was upregulated twofold in the diabetic group. At the same time, 2DM patients and controls show alterations in pro- and anti-inflammatory cytokine levels in the serum.


CONCLUSIONS
This study identifies considerable changes in the expression of transcription factors and extracellular matrix (ECM) components of bone in 2DM patients. Furthermore, the analysis of key differentiation factors of osteoblasts revealed significant alterations in gene expression of these factors, which may contribute to the dysregulation of energy metabolism in 2DM.
Dept. of Trauma Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaninger Straße 22, 81675, Munich, Germany, haug@uchir.me.tum.de.
A T
AT
Haug
K F
KF
Braun
S
S
Ehnert
L
L
Mayer
U
U
Stöckle
A K
AK
Nüssler
S
S
Pscherer
T
T
Freude
D051701:Activating Transcription Factor 4 / Q000235:genetics*; D015153:Blotting, Western; D001847:Bone Diseases / Q000175:diagnosis / Q000235:genetics*; D016001:Confidence Intervals; D016207:Cytokines / Q000378:metabolism; D003720:Densitometry / Q000379:methods; D048909:Diabetes Complications / Q000175:diagnosis / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics*; D008875:Middle Aged; D008967:Molecular Biology; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012016:Reference Values; D050794:STAT1 Transcription Factor / Q000235:genetics*; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D014157:Transcription Factors / Q000235:genetics*
C497109:ATF4 protein, human; D016207:Cytokines; D036961:Matrix Attachment Region Binding Proteins; D012333:RNA, Messenger; C521297:SATB2 protein, human; D050794:STAT1 Transcription Factor; D014157:Transcription Factors; D051701:Activating Transcription Factor 4