TGF-β1 modifications in nuclear matrix proteins of osteoblasts during differentiation

Abstract

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.

Intercellular Adhesion Molecule 1 Discriminates Functionally Different Populations of Human Osteoblasts: Characteristic Involvement of Cell Cycle Regulators

“…It also is reported that direct coculture of osteoblasts and osteoclast precursors induces maturation of osteoclast‐like cells but decreases the ALP activity expressed by osteoblasts (7) . Transforming growth factor β (TGF‐β) increases osteoblast recruitment, differentiation, production of matrix proteins, and modification of mineralization, leading to enhanced trabecular bone formation (40,41) . Interestingly, Jilka et al (42) recently showed that TGF‐β prevents osteoblast apoptosis.…”

Okadaic acid stimulates osteopontin expression through de novo induction of AP‐1

“…Our previous reports showed that the growth factors PDGF‐BB [Kim et al, 1999] and FGF‐2 [Bae et al, 2000] stimulate OP expression in the early stages of MC3T3‐E1 cell differentiation but suppress it strongly in the later mineralization stage. Nuclear matrix components and their organization change dramatically with cell differentiation, and the changes would greatly influence the use of the transcriptional machinery [Lindenmuth et al, 1998]. Thus, OP regulation by growth factors relies on the cellular environment.…”