{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T13:29:39Z","timestamp":1783517379107,"version":"3.55.0"},"reference-count":0,"publisher":"Bioscientifica","issue":"2","content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1996,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The cellular mechanisms involved in the accelerated bone loss occurring in association with estrogen deprivation as seen following the menopause are not fully understood. Insulin-like growth factor-I (IGF-I) is the local regulator of osteoblasts and one of its binding proteins, insulin-like growth factor-binding protein-4 (IGFBP-4), binds to IGF-I and suppresses biological activity. Previous studies have shown that the binding activity of IGFBP-4 in the conditioned medium of parathyroid hormone (PTH)-treated SaOS-2 osteoblastic-like cells is enhanced twofold and that this PTH-enhanced IGFBP-4 binding activity is abolished by 17\u03b2-estradiol. Levels of IGFBP-4 in the conditioned medium have been reported to be regulated not only at the level of production but also at the level of degradation which is catalyzed by a protease that specifically cleaves IGFBP-4. We have, therefore, studied the effects of 17\u03b2-estradiol and PTH on IGFBP-4 protease activity using SaOS-2 cells. SaOS-2 cells produce a protease that specifically cleaves IGFBP-4 into two fragments of approximately 18 and 14 kilodaltons. IGFBP-4 protease activity in the conditioned medium from PTH-treated cells was suppressed, while this PTH-induced suppression of protease activity was reversed by the addition of 17\u03b2-estradiol to the cultures. IGFBP-4 proteolytic activity was stimulated by IGF-I or IGF-II added exogenously and was inhibited by EDTA or protease inhibitors. IGFBP-4 proteolyzed in the conditioned medium from cells treated with PTH and 17\u03b2-estradiol was less effective at inhibiting IGF-I-stimulated [3H]thymidine incorporation into DNA compared with that proteolyzed in the conditioned medium from PTH-treated cells. The simplest explanation is that 17\u03b2-estradiol suppressed the inhibitory effect of PTH on osteoblastic activity by inhibiting the PTH-induced suppression of IGFBP-4 protease activity.<\/jats:p>\n                  <jats:p>Journal of Endocrinology (1996) 150, 223\u2013229<\/jats:p>","DOI":"10.1677\/joe.0.1500223","type":"journal-article","created":{"date-parts":[[2004,12,2]],"date-time":"2004-12-02T18:42:13Z","timestamp":1102012933000},"page":"223-229","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":18,"title":["Regulation of insulin-like growth factor-binding protein-4 protease activity by estrogen and parathyroid hormone in SaOS-2 cells: implications for the pathogenesis of postmenopausal osteoporosis"],"prefix":"10.1530","volume":"150","author":[{"given":"Y","family":"Kudo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Iwashita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Itatsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Iguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Takeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","container-title":["Journal of Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/joe.bioscientifica.com\/view\/journals\/joe\/150\/2\/joe_150_2_007.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.bioscientifica.com\/joe\/article-pdf\/150\/2\/223\/104977\/joe_150_2_007.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.bioscientifica.com\/joe\/article-pdf\/150\/2\/223\/104977\/joe_150_2_007.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T13:09:44Z","timestamp":1783516184000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.bioscientifica.com\/joe\/article\/150\/2\/223\/18639\/Regulation-of-insulin-like-growth-factor-binding"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,8,1]]},"references-count":0,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1996,8,1]]}},"URL":"https:\/\/doi.org\/10.1677\/joe.0.1500223","relation":{},"ISSN":["1479-6805","0022-0795"],"issn-type":[{"value":"1479-6805","type":"electronic"},{"value":"0022-0795","type":"print"}],"subject":[],"published":{"date-parts":[[1996,8,1]]}}}