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.
Thomas A. Linkhart
Donna D. Strong
R. Bruce Wilcox
Doctor of Philosophy (Medical Science)
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
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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.
Merriman, Harold Lyndon, "Proto-oncogene Regulation by Growth Factors in Bone Cells" (1990). Loma Linda University Electronic Theses, Dissertations & Projects. 1437.
Loma Linda University Electronic Theses and Dissertations
Loma Linda University. Del E. Webb Memorial Library. University Archives