TGF-beta1 modifications in nuclear matrix proteins of osteoblasts during differentiation.
Nuclear matrix protein (NMP) composition of osteoblasts shows distinct two-dimensional gel electrophoretic profiles of labeled proteins as a function of stages of cellular differentiation. Because NMPs are involved in the control of gene expression, we examined modifications in the representation of NMPs induced by TGF-beta1 treatment of osteoblasts to gain insight into the effects of TGF-beta on development of the osteoblast phenotype. Exposure of proliferating fetal rat calvarial derived primary cells in culture to TGF-beta1 for 48 h (day 4-6) modifies osteoblast cell morphology and proliferation and blocks subsequent formation of mineralized nodules. Nuclear matrix protein profiles were very similar between control and TGF-beta-treated cultures until day 14, but subsequently differences in nuclear matrix proteins were apparent in TGF-beta-treated cultures. These findings support the concept that TGF-beta1 modifies the final stage of osteoblast mineralization and alters the composition of the osteoblast nuclear matrix as reflected by selective and TGF-beta-dependent modifications in the levels of specific nuclear matrix proteins. The specific changes induced by TGF-beta in nuclear matrix associated proteins may reflect specialized mechanisms by which TGF-beta signalling mediates the alterations in cell organization and nodule formation and/or the consequential block in extracellular mineralization.
Lindenmuth
D
D
Department of Cell Biology and Cancer Center, University of Massachusetts Medical Center, Worcester 01655, USA.
van Wijnen
A J
AJ
Penman
S
S
Stein
J L
JL
Stein
G S
GS
Lian
J B
JB
D000818:Animals; D034961:Antigens, Nuclear; D002454:Cell Differentiation; D015180:Electrophoresis, Gel, Two-Dimensional; D005109:Extracellular Matrix / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D034961:Antigens, Nuclear; D009687:Nuclear Proteins; D016212:Transforming Growth Factor beta