Skeletal site-related variation in human trabecular bone transcriptome and signaling.
BACKGROUND
The skeletal site-specific influence of multiple genes on bone morphology is recognised, but the question as to how these influences may be exerted at the molecular and cellular level has not been explored.


METHODS
To address this question, we have compared global gene expression profiles of human trabecular bone from two different skeletal sites that experience vastly different degrees of mechanical loading, namely biopsies from iliac crest and lumbar spinal lamina.


RESULTS
In the lumbar spine, compared to the iliac crest, the majority of the differentially expressed genes showed significantly increased levels of expression; 3406 transcripts were up- whilst 838 were down-regulated. Interestingly, all gene transcripts that have been recently demonstrated to be markers of osteocyte, as well as osteoblast and osteoclast-related genes, were markedly up-regulated in the spine. The transcriptome data is consistent with osteocyte numbers being almost identical at the two anatomical sites, but suggesting a relatively low osteocyte functional activity in the iliac crest. Similarly, osteoblast and osteoclast expression data suggested similar numbers of the cells, but presented with higher activity in the spine than iliac crest. This analysis has also led to the identification of expression of a number of transcripts, previously known and novel, which to our knowledge have never earlier been associated with bone growth and remodelling.


CONCLUSIONS
This study provides molecular evidence explaining anatomical and micro-architectural site-related changes in bone cell function, which is predominantly attributable to alteration in cell transcriptional activity. A number of novel signaling molecules in critical pathways, which have been hitherto not known to be expressed in bone cells of mature vertebrates, were identified.
Varanasi
Satya S
SS
Musculoskeletal Research Group, Institute of Cellular Medicine, Medical School, Newcastle University, Newcastle Upon Tyne, United Kingdom.
Olstad
Ole K
OK
Swan
Daniel C
DC
Sanderson
Paul
P
Gautvik
Vigdis T
VT
Reppe
Sjur
S
Francis
Roger M
RM
Gautvik
Kaare M
KM
Datta
Harish K
HK
D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism*; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks / Q000235:genetics; D006801:Humans; D008297:Male; D040542:Mechanotransduction, Cellular / Q000235:genetics; D008875:Middle Aged; D009928:Organ Specificity / Q000235:genetics; D010011:Osteocytes / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D013223:Statistics as Topic; D053667:Syndecans / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
D019485:Bone Morphogenetic Proteins; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D053667:Syndecans