Phone: (215) 898-8933
Fax: (215) 898-3695
Position: Professor Appointed: 1976
My laboratory is studying changes in gene expression associated with the formation and maintenance of skeletal tissue. There are currently two major areas of research: identifying the path of osteoblast differentiation from bone marrow stromal cells; changes in gene expression associated with mineralization of extracellular matrix.
The first project derives from the relatively recent finding that, throughout life, there are stem cells in the bone marrow which can give rise to osteoblasts and therefore permit maintenance of our bones. My lab has developed systems for inducing osteoblast differentiation from bone marrow cells in culture. Using these systems, we are analyzing the stages in commitment to the osteoprogenitor lineage, the further steps in differentiation to mature osteoblas ts, the hormones and growth factors that regulate these processes,and the transcription factors controlling commitment to this lineage.
The second project examines the changes in extracellular matrix components and key enzymes of phosphate and calcium metabolism required for calcification of tissues. These studies focus on factors which control whether cartilage will remain uncalcified or will become mineralized. The switch from uncalcified to calcified cartilage is one which occurs normally in the growth plate of bones during growth of an individual; premature calcification during development can lead to shortened stature, while calci fication of cartilage in adults can lead to osteoarthritis. Current studies in my lab examine the role of vitamin C and bone morphogenetic proteins in controlling transcription of key chondrocyte genes as well as their ability to induce cell cycle, matrix, and enzyme changes associated with cartilage mineralization.
1. LEBOY,PS, Grasso-Knight,G, D'Angelo,M, Volk,SW, and Adams,SL.
Smad-RUNX interactions during chondrocyte maturation. J.Bone Joint Surg.
2. D'Angelo, M., Billings,PC, Pacifici,M., LEBOY, PS, and Kirsch,T.
Authentic matrix vesicles contain active metalloproteases. J. Biol. Chem.
276: 11347-11353, 2001.
3. D'Angelo, M., Yan,Z., Nooreyazdan,M., Sarment,D.S., Pacifici,M.,
Billings,P., and LEBOY, P.S. MMP-13 is induced during chondrocyte
hypertrophy. J. Cell. Biochem. 77: 678-693, 2000.
4. Zimmerman, D., Jin, F., LEBOY, P.S., Hardy, S., and Damsky,
Impaired bone formation in transgenic mice resulting from altered integrin
function in osteoblasts. Dev. Biol. 220: 2-15, 2000
5. Volk, S.W., D'Angelo, M., Diefenderfer,D. and Leboy, P.S.
of BMP receptors during chondrocyte maturation. J. Bone and Min. Res. 15:
6.Volk, S.W., LuValle, P., Leask, T., and LEBOY, P.S. A BMP responsive
transcriptional region in the chicken type X collagen gene. J. Bone and
Min. Res. 13: 1521-1529, 1998.
7.Venezian, R.A., Shenker, B.J., Datar,S., and LEBOY, P.S. Modulation
chondrocyte proliferation by ascorbic acid and BMP-2. J Cell. Physiol.
174: 331-341, 1998.
8.Kazhdan, I., Rickard,D. and LEBOY, P.S. HLH transcription
activity in osteogenic cells. J Cell. Biochem. 65: 1-10, 1997.
9.LEBOY, P.S., Sullivan, T.A., Nooreyazdan, M., and Venezian,
chondrocyte maturation by serum-free culture with BMP-2 and ascorbic acid.
J. Cell. Biochem. 66: 394-403, 1997.
10.Sullivan, T.A., Uschmann, B., Hough, R., and LEBOY, P.S. Ascorbate
modulation of chondrocyte gene expression is independent of its role in
collagen secretion. J. Biol. Chem. 269: 22500-22506, 1994.
11. Rickard,D.J., Sullivan, T.A., Shenker, B.J., LEBOY,
Kazhdan, I. Induction of rapid osteoblast differentiation in rat bone
marrow stromal cell cultures by dexamethasone and BMP-2. Dev. Biol.,