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Delineation of Regulatory Networks Underlying BMP Action in Chondrogenesis
Abstract 2005 MHE Conference
T. Michael Underhill1, Linsay M. Drysdale2, Konstantina Karamboulas1,
Matthew F. Cowan1, Jian Wang3, William A. Horton4 and Lisa M. Hoffman2
1 Department of Cellular and Physiological Sciences, University of British Columbia,
Vancouver, BC, Canada, V6T 1Z3; 5C1 2 Department of Physiology, Faculty of Medicine &
Dentistry, University of Western Ontario, London, ON,N6A 3 Robarts Research Institute,
100 Perth Dr., London, ON, Canada, N6A 5K8;4 Shriner’s Children’s Hospital, 3101 SW Sam
Jackson Park Road, Portland, OR, USA, 97239
The BMP and GDF signaling pathways have well-established and essential roles within the developing
skeleton in coordinating formation of cartilaginous anlagen. However, identification of bona fide
targets that underlie the action of these signaling molecules in chondrogenesis has remained elusive.
Using microarray-based methods coupled with functional profiling, we have identified the retinoic acid
(RA) synthesis enzyme, Aldh1a2, as a principal target of BMP signaling—prochondrogenic BMPs or
GDFs lead to attenuation of Aldh1a2 expression and consequently, reduced activation of the retinoid
signaling pathway.
Consistent with this, antagonism of retinoid signaling phenocopies BMP4 action, whereas RA inhibits
the chondrogenic stimulatory activity of BMP4. Further, moderate fold changes in endogenous
retinoid signaling (< 4.5 fold) are sufficient to regulate expression of the chondroblast phenotype.
In aggregate, these results establish a hierarchical relationship between the BMP and retinoid
signaling pathways in chondrogenesis.
These results will be presented along with additional findings that provide a molecular framework for
understanding BMP action in the chondrogenic program.
This research was supported by grants to T.M.U. from the Canadian Institutes of Health Research
and the Canadian Arthritis Network.
Abstract 2005 MHE Conference
T. Michael Underhill1, Linsay M. Drysdale2, Konstantina Karamboulas1,
Matthew F. Cowan1, Jian Wang3, William A. Horton4 and Lisa M. Hoffman2
1 Department of Cellular and Physiological Sciences, University of British Columbia,
Vancouver, BC, Canada, V6T 1Z3; 5C1 2 Department of Physiology, Faculty of Medicine &
Dentistry, University of Western Ontario, London, ON,N6A 3 Robarts Research Institute,
100 Perth Dr., London, ON, Canada, N6A 5K8;4 Shriner’s Children’s Hospital, 3101 SW Sam
Jackson Park Road, Portland, OR, USA, 97239
The BMP and GDF signaling pathways have well-established and essential roles within the developing
skeleton in coordinating formation of cartilaginous anlagen. However, identification of bona fide
targets that underlie the action of these signaling molecules in chondrogenesis has remained elusive.
Using microarray-based methods coupled with functional profiling, we have identified the retinoic acid
(RA) synthesis enzyme, Aldh1a2, as a principal target of BMP signaling—prochondrogenic BMPs or
GDFs lead to attenuation of Aldh1a2 expression and consequently, reduced activation of the retinoid
signaling pathway.
Consistent with this, antagonism of retinoid signaling phenocopies BMP4 action, whereas RA inhibits
the chondrogenic stimulatory activity of BMP4. Further, moderate fold changes in endogenous
retinoid signaling (< 4.5 fold) are sufficient to regulate expression of the chondroblast phenotype.
In aggregate, these results establish a hierarchical relationship between the BMP and retinoid
signaling pathways in chondrogenesis.
These results will be presented along with additional findings that provide a molecular framework for
understanding BMP action in the chondrogenic program.
This research was supported by grants to T.M.U. from the Canadian Institutes of Health Research
and the Canadian Arthritis Network.
Research authored by Dr. Underhill
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List of Publications via PubMed
(NIH National Library of Medicine)
List of Publications via PubMed
(NIH National Library of Medicine)
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Dr. Underhill's research
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Information on The Diseases Database a cross-referenced index of human disease, and the Intute: health & life
sciences a free online service providing access to the very best Web resources for education and research
located in the UK
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