Abstract

Previous studies have shown that bone cells in culture produce a number of growth factors that are important in bone regulation. Chick and mouse primary calvarial cultures consist of a mixture of cell types that make it difficult to interpret the results from these model systems. In contrast, MC3T3-E1 cells are a clonal mouse osteoblast-like cell line. Since MC3T3-E1 cells consist of a single population of calvarial cells, they make an ideal system in which to study the autocrine effects of bone growth factors.

Based on this work, MC3T3-E1 cells are now known to produce IGF-I, TGF-beta and IGF-II in descending order of abundance. These growth factors also act on MC3T3-E1 cells in an autocrine manner. IGF-I and IGF-II increase while TGF-beta decreases cell proliferation as measured by 3H thymidine incorporation. MC3T3-E1 cells also produce two IGF binding proteins--MC-IGFBP-1 and MC-IGFBP-2. The major BP, MC-IGFBP-1, has N-terminal sequence identity with CSF BP which is found in cerebrospinal fluid. The minor BP, MC-IGFBP-2, N-terminal has sequence identity with In-IGFBP which is found in human bone cell conditioned medium. This is the first time that 1) an IGF BP (MC-IGFBP-1) with selective affinity for IGF-II has been shown to be produced by bone cells, and 2) In-IGFBP (MC-IGFBP-2) has been shown to be produced by non-human bone cells.

To determine how growth factors made by MC3T3-E1 cells might act on these cells at the molecular level, the expression of several proto-oncogenes was studied. IGF-I and IGF-II cause a rapid and transient induction of c-fos in MC3T3-E1 cells similar to that observed with other growth factors in other cell types. TGF-beta causes a similar rapid induction of c-fos which is slightly delayed. IGF-I and TGF-beta have no effect on the expression of c-jun and jun-D transcripts, while IGF-II moderately induces these transcripts. In contrast, jun-B transcripts are undetectable with IGF-I and IGF-II, but TGF-beta rapidly and dramatically induces jun-B in MC3T3-E1 cells. Thus, the differences in the c-fos and jun-B inductions may be a component in the molecular mechanism controlling cell proliferation in the MC3T3-E1 cell autocrine system.

LLU Discipline

Biochemistry

Department

Biochemistry

School

Graduate School

First Advisor

Subburaman Mohan

Second Advisor

Thomas A. Linkhart

Third Advisor

Jun-Ichi Ryu

Fourth Advisor

Donna D. Strong

Fifth Advisor

R. Bruce Wilcox

Degree Name

Doctor of Philosophy (Medical Science)

Degree Level

Ph.D.

Year Degree Awarded

1990

Date (Title Page)

8-1990

Language

English

Library of Congress/MESH Subject Headings

Bone and Bones -- physiology; Growth Substances; Proto-oncogenes; Insulin-Life Growth Factor I; Insulin-Life Growth Factor II

Type

Dissertation

Page Count

viii; 150

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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