Temporal expression of pdgf receptors and pdgf regulatory effects
on fetal rat calvarial osteoblastic cells in long-term mineralizing
cultures.
Yu, Xiaohui, Sung-Chih Hsieh, Wei Bao, and Dana T. Graves.
Department of Periodontology and Oral Biology, Boston University
Goldman School of Dental Medicine, Boston, Massachusetts
APStracts 3:0394C, 1996.
PDGF is mitogenic and chemotactic for osteoblastic cells in vitro. It
is expressed during osseous wound healing and stimulates formation of
new bone in vivo. PDGF stimulates cells by binding to specific cell
surface receptors. The purpose of this study was to examine the
effects of PDGF on osteoblastic proliferation and differentiation in
long term mineralizing cultures. Utilizing Northern blot analysis, we
found that continuous PDGF treatment increased histone expression,
indicative of enhanced proliferation, but suppressed osteoblast
differentiation, demonstrated by inhibition of alkaline phosphatase,
type I collagen and osteocalcin expression. The inhibitory effect of
PDGF on the differentiated function of osteoblasts was further
established by findings that P PDGF significantly inhibited nodule
formation. The expression of PDGF receptors varied at different
stages of culture. PDGF receptor mRNA expression increased when the
cells had achieved a mature phenotype, during the stage of matrix
maturation, then decreased. However, as demonstrated by thymidine
incorporation assays, the capacity of PDGF to stimulate DNA synthesis
actually decreased during osteoblast maturation, as receptor
expression increased. To investigate this apparent contradiction,
tyrosyl phosphorylation was determined by immunoblot assays to assess
changes in PDGF activation of their cognate receptors. The pattern of
PDGF-induced tyrosyl phosphorylation remained relatively constant.
This suggests suggesting that the diminished mitogenic activity of
response to PDGF that occurs following osteoblast differentiation
occurs is regulated at a post-receptor level.
Received 23 September 1996; accepted in final form 4 December
1996.
APS Manuscript Number C550-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996