{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T15:04:52Z","timestamp":1706713492224},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,2,4]],"date-time":"2005-02-04T00:00:00Z","timestamp":1107475200000},"content-version":"vor","delay-in-days":7400,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[1984,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The mitogenic activity of somatomedin\u2010C\/insulinlike growth factor\u2010I (SM\u2010C\/IGF\u2010I) appears to be greatly influenced by cell culture conditions, especially the presence of other growth factors and nutrients in the culture medium. To investigate the effect of cell density on SM\u2010C\/IGF\u2010I activity, we have evaluated SM\u2010C\/IGF\u2010I binding and stimulation of DNA synthesis and cell replication as a function of cell density in cultured human fibroblast monolayers. At fibroblast concentrations of 2.7 \u00d7 10<jats:sup>5<\/jats:sup> and 1.48 \u00d7 10<jats:sup>6<\/jats:sup> cells per 60\u2010mm dish, specific binding of [<jats:sup>125<\/jats:sup>I]SM\u2010C\/IGF\u2010I per 10<jats:sup>6<\/jats:sup> cells was 170% higher in sparse than dense monolayers (9.3% vs. 3.4%). Increased binding in sparse monolayers was attributable to approximately twice as many receptors in sparse as in dense cells (31,000 vs. 16,000 sites per cell), as well as to a modest increase in the affinity constant. Similarly, half\u2010maximal stimulation of [methyl\u2010<jats:sup>3<\/jats:sup>H]thymidine incorporation was achieved at SM\u2010C\/IGF\u2010I concentrations of 2.5 ng\/ml in sparse cells but required 20 ng\/ml in dense cells. Although this required only 45% occupancy of membrane receptors on sparse cells, and almost 80% occupancy on dense cells, the total number of occupied receptors was similar in both sparse and dense cells (approximately 13,000 receptors\/cell for half\u2010maximal stimulation). The presence of increased numbers of \u201cfunctional receptors\u201d on sparse fibroblasts thus results in enhanced sensitivity to SM\u2010C\/IGF\u2010I stimulation of DNA synthesis and cell replication. Progressive decreases in the number of functional receptors, secondary to cell crowding, may contribute to density\u2010dependent inhibition of fibroblast growth.<\/jats:p>","DOI":"10.1002\/jcp.1041210221","type":"journal-article","created":{"date-parts":[[2005,2,26]],"date-time":"2005-02-26T14:21:37Z","timestamp":1109427697000},"page":"419-424","source":"Crossref","is-referenced-by-count":17,"title":["Density\u2010associated loss of functional receptors for somatomedin\u2010C\/insulinlike growth factor I (SM\u2010C\/IGF\u2010I) on cultured human fibroblast monolayers"],"prefix":"10.1002","volume":"121","author":[{"given":"Ron G.","family":"Rosenfeld","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura A.","family":"Dollar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheryl A.","family":"Conover","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,2,4]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.77.11.6644"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041160210"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-50-4-690"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/235107a0"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI108816"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-54-2-442"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/258487a0"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.74.11.5046"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/194495a0"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-113-1-228"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/269155a0"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1040890305"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1040790302"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-39-3-512"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-55-3-434"},{"key":"e_1_2_1_17_1","first-page":"502","article-title":"Normal somatomedin\u2010C\/insulin\u2010like growth factor I binding and action in cultured human fibroblasts from Turner syndrome","volume":"104","author":"Rosenfeld R. G.","year":"1983","journal-title":"Acta Endocrinol. (Copenhagen)"},{"key":"e_1_2_1_18_1","first-page":"825","article-title":"A hormonally controlled serum factor which stimulates sulfate incorporation by cartilage in vitro","volume":"49","author":"Salmon W. D.","year":"1957","journal-title":"J. Lab. Clin. Med."},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1949.tb27297.x"},{"key":"e_1_2_1_20_1","first-page":"21","article-title":"Effect of purified somatomedins on thymidine incorporation into lectin\u2010activated human lymphocyes","volume":"102","author":"Schimpff R\u2010M.","year":"1983","journal-title":"Acta Endocrinol. (Copenhagen)"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.76.3.1279"},{"key":"e_1_2_1_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/246200a0"},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(76)90154-9"},{"key":"e_1_2_1_24_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI110383"},{"key":"e_1_2_1_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.74.4.1619"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcp.1041210221","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.1041210221","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,20]],"date-time":"2023-10-20T16:36:06Z","timestamp":1697819766000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.1041210221"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1984,11]]},"references-count":24,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1984,11]]}},"alternative-id":["10.1002\/jcp.1041210221"],"URL":"https:\/\/doi.org\/10.1002\/jcp.1041210221","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[1984,11]]}}}