Changes in IGF-I and -II expression and secretion during the proliferation and differentiation of normal rat osteoblasts

R. S. Birnbaum, R. R. Bowsher, Kristine Wiren

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Abstract

IGF-I and -II have potent effects on proliferation and differentiation of osteoblasts in vitro. These cells secrete both IGFs and expression of these peptides is regulated by several of the hormones and growth factors that promote bone resorption and/or formation. However, the physiological role(s) of IGFs in the remodelling process of adult bone is still unclear. Some confusion may arise from results influenced, in part, by differences in the state of osteoblast development of in vitro cultures. Several laboratories have demonstrated that murine osteoblast cultures progress from proliferating preosteoblasts, to mature differentiated osteoblasts that form an extracellular matrix, to cultures that form a mineralized matrix. We have recently documented changes in IGF-binding protein expression and secretion in these cultures. To complement and extend this work, we have examined IGF-I expression and secretion and IGF-II expression during in vitro osteoblast development. Steady-state mRNA levels of both IGF-I and -II increased from the earliest time examined, day 5 in culture, to a maximum at day 11 and, thereafter, declined. IGF-I secreted into the medium also changed in a biphasic manner, but IGF-II could not be quantitated due to the sensitivity of our assay. Secretion of IGF-I was lowest between days 8 and 14. IGF-I secretion on day 5 was significantly greater than day 8. Similarly, IGF-I secretion from day 17 to 26 was also greater than observed for days 8 to 14. If differentiation of the cells was inhibited, this late rise in IGF-I secretion was abolished. We conclude that IGF-I is an autocrine mitogen of the proliferating preosteoblasts. Further, we also suggest that the rise in IGF-I secretion, late in osteoblast development, may lead to sequestration of this mitogen in the extracellular matrix for release during a subsequent remodelling cycle.

Original languageEnglish (US)
Pages (from-to)251-259
Number of pages9
JournalJournal of Endocrinology
Volume144
Issue number2
StatePublished - 1995

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Insulin-Like Growth Factor II
Osteoblasts
Insulin-Like Growth Factor I
Mitogens
Extracellular Matrix
Insulin-Like Growth Factor Binding Proteins
Bone Resorption
Osteogenesis
Cell Differentiation
Intercellular Signaling Peptides and Proteins
Hormones
Bone and Bones
Messenger RNA
Peptides

ASJC Scopus subject areas

  • Endocrinology

Cite this

Changes in IGF-I and -II expression and secretion during the proliferation and differentiation of normal rat osteoblasts. / Birnbaum, R. S.; Bowsher, R. R.; Wiren, Kristine.

In: Journal of Endocrinology, Vol. 144, No. 2, 1995, p. 251-259.

Research output: Contribution to journalArticle

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