Bone Morphogenetic Proteins (BMPs) induce bone formation by
osteoblasts, but their direct role in bone resorption by osteoclasts remains to be
characterized. Twisted Gastrulation (Twsg1) is a secreted BMP binding protein
that inhibits BMPs from binding to their receptors. Mice lacking the Twsg1 gene
(Twsg1-/-) exhibit an osteopenic skeletal defect. Previous studies indicate that the
osteopenic phenotype in Twsg1-/- mice is due to increased osteoclastogenesis and
not due to reduced osteoblast function. This study hypothesizes that treatment of
wild-type osteoclasts with BMP2 will increase osteoclast gene expression and that
this gene expression will decrease with the addition of the known BMP inhibitor,
Noggin. The results of this investigation show that the addition of BMP2 to
RANKL upregulates Cathepsin K, Nfatc1, Acp5, DCSTAMP, and ATP6v6d02
gene expression levels. The addition of the more well understood BMP inhibitor,
Noggin, downregulates these gene expression levels. These results indicate a
possible direct mechanism of action for BMP2 on osteoclast activation.
University of Minnesota M.S. thesis. November 2009. Major: Dentistry. Advisors:Dr. Brent Larson and Dr. John Beyer. 1 computer file (PDF); vi, 39 pages. Ill. (some col.)
Espe, Kelly Christine.
Bone Morphogenetic Protein-2 (BMP2) upregulates osteoclast gene expression..
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