Areas of Interest
Defining and evaluating function of the osteocyte restricted
genes
Osteocytes are terminally differentiated cells of the osteoblast
lineage. It is well known that bone tissue has the capacity to
alter its mass and structure in response to mechanical strain
using osteocytes as mechanosensory cells. Identification of
genes involved in these processes requires isolation of a pure
population of osteocytes and a comparison to the gene expression
profile to cells at other maturation stages of the osteoblast
lineage. In this project we aim to evaluate the gene expression
profile of an isolated osteocyte population and contrast its
gene expression to osteoblasts as they transition into the
osteocyte stage. The analysis of their gene expression profile
provides important information for a better understanding of the
mechanisms that regulate bone mass.
Myofibroblast/pericyte as an mesenchymal progenitor cell
Adult mesenchymal progenitor cells have enormous potential for
use in reparative medicine. The easy access and isolation of
bone marrow aspirate or liposuction collection have made these
cells a prime target for studies of differentiation into various
adult mesenchymal tissues for regenerative medicine purposes. To
define a population of myofibroblasts/pericyte we are utilizing
previously developed transgenic mice in which this cell type is
identified by a smooth muscle α-actin promoter GFP transgene
expression (αSMAGFP). To define the differentiation ability of
these cells, we are using osteoblast/adipocyte/chondrocyte
specific promoters driving GFP that we have previously
characterized. These transgenes activate at mature stages of the
lineage differentiation and by combining complementary colors,
we can test for the ability of isolated αSMA+ cells to progress
from a progenitor to fully mature bone, fat or cartilage.
Regenerative potential of periodontal progenitor cells
The process of tissue regeneration in craniofacial bone requires
the identification of optimal progenitor cells, and the
evaluation of their potential in clear models of new bone
formation. The periodontal ligament (PDL) contains a progenitor
population that can differentiate into osteoblasts,
cementoblasts and a mature periodontal ligament cells. PDL cells
are easily accessible at the time of tooth extraction, and
following expansion and long-term storage; they could be used
for bone regeneration or enhancement of bone in preparation for
placement of dental implants. Any broad clinical utility
requires exploring this source of progenitor cells, their true
identity and definition of their progeny. Obstacles to these
goals are the inability to identify and purify the progenitor
cells from PDL, and the lack of the in vivo markers that can be
used to confirm that progenitor cells can attain the state and
functionality of terminally differentiated phenotypes. In
addition an extensive comparison of osteogenic capacity between
the mesenchymal progenitor cells derived from PDL or from adult
bone marrow and adipose derived stromal cells has to be
completed.
Selected Publications
Kalajzic, Z., Li, H., Wang, L., Jiang, X., Lamothe, K., Adams,
DJ., Aguila, HL., Rowe, DW. and Kalajzic, I. Use of an
alpha-smooth muscle actin (α-SMA) GFP reporter to identify an
osteoprogenitor population. Bone. 2008 Sep;43(3):501-10.
Li, H., Marijanovic, I., Kronenberg, MS., Erceg, I., Stover,
ML., Velonis, D., Mina, M., Upholt, WB., Kalajzic, I., and AC.
Lichtler. Expression and Function of Dlx Genes in the Osteoblast
Lineage. Developmental Biology, 316; 2008 458–470.
Kalajzic, I., Staal, A., Yang, W., Wu, Y., Johnson, S.E.,
Feyen, J.H.M., Krueger, W., Maye, P., Yu, F., Zhao, Y., Kuo, L.,
Gupta, R.R., Achenie, L.E.K., Wang, H., Shin, D. and Rowe, D.W.
Expression profile of osteoblast lineage at defined stages of
differentiation. J Biol Chem. 2005, July 1; 280(26):24618-24627.
Yang W, Lu Y, Kalajzic I, Guo D, Harris MA, Gluhak-Heinrich
J, Kotha S, Bonewald LF, Feng JQ, Rowe DW, Turner CH, Robling
AG, Harris SE. Dentin matrix protein 1 gene cis-regulation. J
Biol Chem. 2005, May 27;280(21):20680-90.
Kalajzic, I., Braut, A., Guo D., Xi, J., Kronenberg, M.S.,
Mina, M., Harris MA, Harris, S.E. and Rowe, D.W. Dentin Matrix
Protein 1 Expression During Osteoblastic Differentiation:
generation of an osteocyte GFP-transgene. Bone. 2004. 35, 74-82.
Kalajzic I., Kalajzic Z., Hurley, M.M., Lichtler A.C. and
Rowe D.W. Stage specific inhibition of osteoblast lineage
differentiation by FGF2 and noggin. J of Cell Biochem. 2003. 88,
(6) 1168-1176.
Kalajzic, I., Terzic, J., Rumboldt, Z., Mack, K., Naprta, A.,
Ledgard, F., Gronowicz, G., Clark, S.H. and Rowe, D.W.
Osteoblastic Response to the Defective Matrix in the
Osteogenesis Imperfecta Murine (OIM) Mouse. 2002 Endocrinology,
143 (5) 1594-1601.
Kalajzic, I., Kalajzic, Z., Kaliterna, M., Gronowicz, G.,
Clark, S.H., Lichtler, A.C. and Rowe, D.W. Use of Col1a1GFP
transgenes to identify subpopulations of cells at different
stages of the osteoblast lineage. J Bone Miner Res.
2002,17:15-25. |
