Differentiation dependent expression of urocortin's mRNA and peptide in human osteoprogenitor cells: influence of BMP-2, TGF-beta-1 and dexamethasone.
Urocortin-1 (UCN) a corticotropin releasing-factor (CRF) related peptide, has been found to be expressed in many different tissues like the central nervous system, the cardiovascular system, adipose tissue, and skeletal muscle. The effects of UCN are mediated via stimulation of CRF-receptors 1 and 2 (CRFR1 and 2, CRFR's) with a high affinity for CRFR2. It has been shown that the CRF-related peptides and CRFR's are involved in the regulation of stress-related endocrine, autonomic and behavioural responses. Using immunocytochemistry, immunohistochemistry and RT-PCR, we now can show the differentiation dependent expression of UCN mRNA and peptide in human mesenchymal progenitor cells (MSCs) directed to the osteoblastic phenotype for the first time. UCN expression was down regulated by TGF-beta and BMP-2 in the early proliferation phase of osteoblast development, whereas dexamethasone (dex) minimally induced UCN gene expression during matrix maturation after 24 h stimulation. Stimulation of MSCs for 28 days with ascorbate/beta-glycerophosphate (asc/bGp) induced UCN gene expression at day 14. This effect was prevented when using 1,25-vitamin D3 or dex in addition. There was no obvious correlation to osteocalcin (OCN) gene expression in these experiments. In MSCs from patients with metabolic bone disease (n = 9) UCN gene expression was significantly higher compared to MSCs from normal controls (n = 6). Human MSCs did not express any of the CRFR's during differentiation to osteoblasts. Our results indicate that UCN is produced during the development of MSCs to osteoblasts and differentially regulated during culture as well as by differentiation factors. The expression is maximal between proliferation and matrix maturation phase. However, UCN does not seem to act on the osteoblast itself as shown by the missing CRFR's. Our results suggest new perspectives on the role of urocortin in human skeletal tissue in health and disease.
Tezval
Mohammad
M
Department of Trauma, Plastic and Reconstructive Surgery, Goettingen University Hospital, University Medicine Goetingen, Robert Koch Str. 40, 37075 Goettingen, Germany. mtezval@med.uni-goettingen.de
Tezval
Hossein
H
Dresing
Klaus
K
Stuermer
Ewa Klara
EK
Blaschke
Martina
M
Stuermer
Klaus Michael
KM
Siggelkow
Heide
H
D000328:Adult; D000368:Aged; D001851:Bone Diseases, Metabolic / Q000235:genetics / Q000473:pathology; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D009928:Organ Specificity / Q000235:genetics; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D054832:Urocortins / Q000235:genetics* / Q000378:metabolism
D055396:Bone Morphogenetic Protein 2; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D053773:Transforming Growth Factor beta1; D054832:Urocortins; D003907:Dexamethasone