{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T06:18:34Z","timestamp":1778566714819,"version":"3.51.4"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[1994,6,1]],"date-time":"1994-06-01T00:00:00Z","timestamp":770428800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1994,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>It has been suggested that one of the mechanisms by which estrogen protects against postmenopausal osteoporosis is by modulating the production of cytokines, such as interleukin-1 (IL-1), tumor necrosis factors (TNF), and interleukin-6 (IL-6), in the bone microenvironment. In this study, reverse transcription\/polymerase chain reaction (RT\/PCR) was used to analyze expression of the mRNAs encoding these cytokines in freshly isolated human bone biopsy samples. Marked differences were found in the prevalence with which certain cytokines were expressed in different patient subgroups. Specifically, IL-1\u03b1, IL-1\u03b2, and IL-6 mRNAs were expressed significantly more often in bone samples from postmenopausal women with osteoporotic fractures than in postmenopausal women with normal bone density or postmenopausal women on hormone replacement therapy (HRT). The prevalence of IL-1\u03b1 expression was 54% in bone samples from patients with osteoporotic fractures (n = 22), compared with 30% in nonosteoporotic postmenopausal patients (n = 10) and 10% in postmenopausal patients on HRT (difference between groups by \u03c7 test = 7.0; DF = 2,p &amp;lt; 0.05). Corresponding figures for IL-1\u03b2 were 54 versus 30 versus 0% (\u03c7 = 8.6; DF = 2, p &amp;lt; 0.01) and, for IL-6, 94 versus 51 versus 40%; \u03c7 = 13.5; DF = 2, p &amp;lt; 0.01). TNF-\u03b1 was expressed in a similar proportion of osteoporotic (63%) and normal postmenopausal patients (60%), whereas only 10% of HRT-treated patients showed expression of TNF-\u03b1 (\u03c7 = 8.2; DF = 2, p &amp;lt; 0.05). TNF-\u03b2 was less commonly expressed in osteoporosis (18%) and was not detected at all in normal postmenopausal or HRT-treated patients, but this difference was not significant. Cytokine expression in bone samples from young healthy individuals showed sex-dependent differences in cytokine expression. In males, the pattern was similar to that observed in normal postmenopausal patients, with IL-1\u03b1 expression in 36%, IL-1\u03b2 in 36%, TNF-\u03b1 in 63%, TNF-\u03b2 in 9%, and IL-6 in 54% of cases. In young females (n = 7), however, the patterns of expression were similar to those in the HRT group, with IL-1\u03b1 expression in 28%, IL-1\u03b2 in 14%; TNF-\u03b1 in 43%, TNF-\u03b2 in 6%, and IL-6 in 28%. These experiments demonstrate that several cytokine mRNAs are expressed in the bone microenvironment. The high proportion of osteoporotic biopsies that showed expression of IL-1\u03b1, IL-1\u03b2, TNF-\u03b1, and IL-6 mRNAs lends support to the hypothesis that activation of cytokine expression in bone is a feature of postmenopausal osteoporosis and raises the possibility that local release of these cytokines contributes to bone loss in this condition.<\/jats:p>","DOI":"10.1002\/jbmr.5650090614","type":"journal-article","created":{"date-parts":[[2010,2,3]],"date-time":"2010-02-03T16:32:53Z","timestamp":1265214773000},"page":"883-890","source":"Crossref","is-referenced-by-count":143,"title":["Analysis of gene expression in human bone biopsies by polymerase chain reaction: Evidence for enhanced cytokine expression in postmenopausal osteoporosis"],"prefix":"10.1093","volume":"9","author":[{"given":"Stuart H.","family":"Ralston","sequence":"first","affiliation":[{"name":"Department of Medicine and Therapeutics, Forresterhill Hospital Aberdeen, Scotland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[1994,6,1]]},"reference":[{"key":"2024013113134158000_bib1","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1056\/NEJM198803313181305","article-title":"Local and systemic factors in the pathogenesis of osteoporosis","volume":"318","author":"Raisz","year":"1988","journal-title":"N Engl J Med"},{"key":"2024013113134158000_bib2","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1172\/JCI113318","article-title":"Growth factors and bone remodelling","volume":"81","author":"Canalis","year":"1988","journal-title":"J Clin Invest"},{"key":"2024013113134158000_bib3","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1172\/JCI115584","article-title":"Interleukin-6: A potential autocrine\/paracrine factor in Paget's disease of bone","volume":"89","author":"Roodman","year":"1992","journal-title":"J Clin Invest"},{"key":"2024013113134158000_bib4","volume-title":"Cytokines and Bone Metabolism","author":"Gowen","year":"1992"},{"key":"2024013113134158000_bib5","doi-asserted-by":"crossref","first-page":"4616","DOI":"10.1073\/pnas.84.13.4616","article-title":"Spontaneous release of interleukin-1 from human blood monocytes reflects bone formation in idiopathic osteoporosis","volume":"84","author":"Pacifici","year":"1987","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024013113134158000_bib6","doi-asserted-by":"crossref","first-page":"2398","DOI":"10.1073\/pnas.86.7.2398","article-title":"Ovarian steroid treatment blocks a postmenopausal increase in blood interleukin-1 release","volume":"86","author":"Pacifici","year":"1989","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024013113134158000_bib7","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1016\/S0015-0282(16)59945-2","article-title":"Gonadal steroids modulate human monocyte interleukin-1 (IL-1) activity","volume":"49","author":"Polan","year":"1988","journal-title":"Fertil Steril"},{"key":"2024013113134158000_bib8","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1210\/jcem-69-6-1200","article-title":"Progesterone and estradiol modulate interleukin-1 messenger ribonucleic acid levels in cultured human peripheral monocytes","volume":"89","author":"Polan","year":"1989","journal-title":"J Clin Endocrinol Metab"},{"key":"2024013113134158000_bib9","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1002\/jbmr.5650050912","article-title":"Estrogen inhibits release of tumor necrosis factor from peripheral blood mononuclear cells in postmenopausal women","volume":"5","author":"Ralston","year":"1990","journal-title":"J Bone Miner Res"},{"key":"2024013113134158000_bib10","first-page":"54","article-title":"Estradiol modulates the synthesis of tumor necrosis factor but not interleukin-6 by adult human osteoblasts in vitro","volume":"1","author":"Rickard","year":"1990","journal-title":"Osteoporosis Int"},{"key":"2024013113134158000_bib11","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1172\/JCI115668","article-title":"17-Beta estradiol inhibits interleukin-6 production by bone-marrow-derived stromal cells and osteoblasts in vitro: A potential mechanism for the anti-osteoporotic effect of estrogens","volume":"8","author":"Girasole","year":"1992","journal-title":"J Clin Invest"},{"key":"2024013113134158000_bib12","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1126\/science.1621100","article-title":"Increased osteoclast development after estrogen loss\u2014mediation by interleukin-6","volume":"257","author":"Jilka","year":"1992","journal-title":"Science"},{"key":"2024013113134158000_bib13","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1126\/science.8480174","article-title":"Cytokines and estrogen in bone: Anti-osteoporotic effects","volume":"260","author":"Horowitz","year":"1993","journal-title":"Science"},{"key":"2024013113134158000_bib14","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/0003-2697(87)90021-2","article-title":"Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction","volume":"162","author":"Chomczynski","year":"1987","journal-title":"Anal Biochem"},{"key":"2024013113134158000_bib15","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/339237a0","article-title":"Avoiding false positives with PCR","volume":"339","author":"Kwok","year":"1989","journal-title":"Nature"},{"key":"2024013113134158000_bib16","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1093\/nar\/12.1Part1.387","article-title":"A comprehensive set of sequence analysis programs for the Vax","volume":"12","author":"Devereaux","year":"1984","journal-title":"Nucleic Acids Res"},{"key":"2024013113134158000_bib17","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1084\/jem.174.2.493","article-title":"Cytokine gene transcription in vascularised organ grafts: Analysis using semiquantitative polymerase chain reaction","volume":"174","author":"Dallman","year":"1991","journal-title":"J Exp Med"},{"key":"2024013113134158000_bib18","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/978-1-349-20235-5_8","volume-title":"PCR Technology","author":"Kawasaki","year":"1989"},{"issue":"Suppl. 1","key":"2024013113134158000_bib19","first-page":"154","article-title":"Infusion of IL-1 receptor antagonist increases bone density in ovariectomized rats","volume":"50","author":"Kimble","year":"1992","journal-title":"Calcif Tissue Int"},{"key":"2024013113134158000_bib20","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1210\/jcem-68-2-364","article-title":"Effect of estrogen in vivo and in vitro on spontaneous interleukin-1 release by monocytes from post-menopausal women","volume":"68","author":"Stock","year":"1989","journal-title":"J Clin Endrocrinol Metab"},{"issue":"Suppl. 1","key":"2024013113134158000_bib21","first-page":"S166","article-title":"Interleukin-1 receptor antagonist but not anti IL-6 antibody blocks ovariectomy induced osteoclast formation and bone resorption in mice. (abstract)","volume":"8","author":"Kitazawa","year":"1993","journal-title":"J Bone Miner Res"},{"key":"2024013113134158000_bib22","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1172\/JCI114975","article-title":"Bone matrix constituents stimulate interleukin-1 release from human blood mononuclear cells","volume":"87","author":"Pacifici","year":"1990","journal-title":"J Clin Invest"},{"key":"2024013113134158000_bib23","first-page":"1","volume-title":"Cytokines and Bone Metabolism","author":"Skjodt","year":"1992"}],"container-title":["Journal of Bone and Mineral Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjbmr.5650090614","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/9\/6\/883\/56495906\/5650090614.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/9\/6\/883\/56495906\/5650090614.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T14:58:27Z","timestamp":1710341907000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/9\/6\/883-890\/7380822"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,6,1]]},"references-count":23,"journal-issue":{"issue":"6","published-online":{"date-parts":[[1994,6,1]]},"published-print":{"date-parts":[[1994,6,1]]}},"URL":"https:\/\/doi.org\/10.1002\/jbmr.5650090614","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[1994,6,1]]},"published":{"date-parts":[[1994,6,1]]}}}