Areas of Interest
We are interested in understanding how components of the
extracellular matrix regulate the behavior of normal bone cells
and cancer cells. We use the matricellular glycoprotein
osteonectin or SPARC as a paradigm for these studies, since this
protein can modulate cell behavior as well as play an
organizational role in the matrix. Osteonectin is widely
expressed in areas of active remodeling and cellular stress in
multiple organ systems. We found that osteonectin is critical
for the maintenance of bone mass, and for the appropriate
response of the skeleton to bone-anabolic PTH therapy.
Importantly, functional SNPs (single nucleotide polymorphisms)
in the 3’ untranslated region (UTR) of osteonectin are
associated with bone mass in a subset of osteoporosis patients.
Our present studies are focused on understanding how these SNPs
regulate gene expression in vitro and in vivo. In addition, we
found that a specific family of microRNAs (miRNAs) acts as
negative regulators of osteonectin expression in osteoblasts. We
are characterizing the mechanisms regulating the expression of
these miRNAs in bone cells, and determining other genes that may
also be regulated by these miRNAs. Lastly, we are interested in
understanding how bone matrix composition and organization
impacts the growth and survival of prostate carcinoma cells in
the skeleton. Bone-metastatic prostate carcinoma cells often
create an “osteoblastic response”, resulting in the deposition
of a disorganized bone matrix. We will determine whether this
matrix can preferentially support cancer cell survival. Our
research makes use of novel in vitro and in vivo models.
Lab Rotation Projects
Students with their own questions on how the extracellular
matrix modules cell function are welcome. Projects already
available in the lab include:
1. Determine how osteonectin supports the survival of bone
cells.
2. Determine the impact of bone matrix organization on the
behavior and survival of metastatic prostate carcinoma cells.
3. Determine how SNPs in the osteonectin 3’ UTR modulate gene
expression in vivo.
4. Determine the mechanisms regulating the miR-29 family in
osteoblasts.
Selected Publications
Kapinas K., Kessler C.B., Shubert-Coleman J., Delany A.M.
miR-29 suppresses osteonectin in response to FGF-2 and during
osteoblastic differentiation. Under revision
Machado do Reis L., Kessler C.B., Adams D.J., Lorenzo J.,
Jorgetti V., Delany A.M. Accentuated osteoclastic response to
parathyroid hormone undermines bone mass acquisition in
osteonectin-null mice. Bone 43:264-23, 2008.
Delany, A.M., McMahon D.J., Powell, J.S., Greenberg, D.A.,
Kurland, E.S. Osteonectin/SPARC polymorphisms in Caucasian men
with idiopathic osteoporosis. Osteoporosis International
19:969-978, 2008.
Kessler, C.B. and Delany, A.M. Increased notch 1 expression
and attenuated stimulatory G protein coupling to adenylyl
cyclase in osteonectin-null osteoblasts. Endocrinology
148:1665-1674, 2007.
Delany, A.M., Kalajzic, I., Bradshaw A.D., Sage, E.H.,
Canalis, E. Osteonectin-null mutation compromises osteoblast
formation, maturation, and survival. Endocrinology
144:2588-2596, 2003.
Boskey A.L., Moore D.J., Amling M., Canalis E., Delany A.M.
Infrared analysis of the mineral and matrix in bones of
osteonectin-null mice and their wild type controls. J. Bone
Miner. Res. 18:1005-1011, 2003.
Revised August, 2008. |
