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.
","abstract_html":"<p>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.</p> <p>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 <sup>3</sup>H 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.</p> <p>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.</p>","abstract_has_math":false,"creators":["Merriman, Harold Lyndon"],"institution":null,"degree_name":"Doctor of Philosophy (Medical Science)","degree_level":"Dissertation","degree_discipline":"Biochemistry","degree_department":null,"school":null,"contributors":["Subburaman Mohan","Thomas A. Linkhart","Jun-Ichi Ryu","Donna D. Strong","R. Bruce Wilcox"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":1990,"date_issued":"1990-08-01T07:00:00Z","date_published":"1990-08-01T07:00:00Z","updated_at":"2026-07-24T02:53:44Z","subjects":["Animal Experimentation and Research","Biochemistry","Medical Cell Biology","Bone and Bones -- physiology; Growth Substances; Proto-oncogenes; Insulin-Life Growth Factor I; Insulin-Life Growth Factor II"],"languages":["English"],"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."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://scholarsrepository.llu.edu/etd/1437","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Subburaman Mohan","Thomas A. 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Bruce Wilcox"]},{"key":"dc:creator","label":"Author","values":["Merriman, Harold Lyndon"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"thesis:degree_discipline","label":"Discipline","values":["Biochemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (Medical Science)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Animal Experimentation and Research","Biochemistry","Medical Cell Biology","Bone and Bones -- physiology; Growth Substances; Proto-oncogenes; Insulin-Life Growth Factor I; Insulin-Life Growth Factor II"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["English"]},{"key":"dc:rights","label":"Dc Rights","values":["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."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://scholarsrepository.llu.edu/etd/1437"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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.
"]},{"key":"dc:title","label":"Title","values":["Proto-oncogene Regulation by Growth Factors in Bone Cells"]}]}],"canonical_facts":{"dc:contributor":["Subburaman Mohan","Thomas A. Linkhart","Jun-Ichi Ryu","Donna D. Strong","R. Bruce Wilcox"],"dc:creator":["Merriman, Harold Lyndon"],"dc:description.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.
"],"dc:identifier":["https://scholarsrepository.llu.edu/etd/1437"],"dc:language":["English"],"dc: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."],"dc:subject":["Animal Experimentation and Research","Biochemistry","Medical Cell Biology","Bone and Bones -- physiology; Growth Substances; Proto-oncogenes; Insulin-Life Growth Factor I; Insulin-Life Growth Factor II"],"dc:title":["Proto-oncogene Regulation by Growth Factors in Bone Cells"],"thesis:degree_discipline":["Biochemistry"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (Medical Science)"]},"updated_at":"2026-07-24T02:53:44Z"}