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





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


Year Degree Awarded


Date (Title Page)




Library of Congress/MESH Subject Headings

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



Page Count

viii; 150

Digital Format


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.


Loma Linda University Electronic Theses and Dissertations

Collection Website



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