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Curcumin circulates as an inactive glucuronide that can be deconjugated in situ by bone's high \u03b2\u2010glucuronidase (GUSB) content, forming the active aglycone. Because curcumin is a common remedy for musculoskeletal disease, effects of microenvironmental changes consequent to skeletal development or disease on bone curcumin metabolism are explored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      Across sexual\/skeletal development or between sexes in C57BL\/6 mice ingesting curcumin (500\u00a0mg kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      ), bone curcumin metabolism and GUSB enzyme activity are unchanged, except for &gt;twofold higher (\n                      <jats:italic>p<\/jats:italic>\n                      &lt;\u00a00.05) bone curcumin\u2010glucuronide substrate levels in immature (4\u20136\u2010week\u2010old) mice. In ovariectomized (OVX) or bone metastasis\u2010bearing female mice, bone substrate levels are also &gt;twofold higher. Aglycone curcumin levels tend to increase proportional to substrate such that the majority of glucuronide distributing to bone is deconjugated, including OVX mice where GUSB decreases by 24% (\n                      <jats:italic>p<\/jats:italic>\n                      &lt;\u00a00.01). GUSB also catalyzes deconjugation of resveratrol and quercetin glucuronides by bone, and a requirement for the aglycones for anti\u2010osteoclastogenic bioactivity, analogous to curcumin, is confirmed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Dietary polyphenols circulating as glucuronides may require in situ deconjugation for bone\u2010protective effects, a process influenced by bone microenvironmental changes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mnfr.202000072","type":"journal-article","created":{"date-parts":[[2020,6,7]],"date-time":"2020-06-07T10:00:46Z","timestamp":1591524046000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Bone\u2010Specific Metabolism of Dietary Polyphenols in Resorptive Bone Diseases"],"prefix":"10.1002","volume":"64","author":[{"given":"Andrew G.","family":"Kunihiro","sequence":"first","affiliation":[{"name":"Department of Nutritional Sciences University of Arizona  Tucson AZ 85721 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula B.","family":"Luis","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Vanderbilt University  Nashville TN 37232 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer B.","family":"Frye","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Arizona  Tucson AZ 85724 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wade","family":"Chew","sequence":"additional","affiliation":[{"name":"University of Arizona Cancer Center University of Arizona  Tucson AZ 85719 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. H.","family":"Chow","sequence":"additional","affiliation":[{"name":"University of Arizona Cancer Center University of Arizona  Tucson AZ 85719 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4215-967X","authenticated-orcid":false,"given":"Claus","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Vanderbilt University  Nashville TN 37232 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9826-5407","authenticated-orcid":false,"given":"Janet L.","family":"Funk","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences University of Arizona  Tucson AZ 85721 USA"},{"name":"Department of Medicine University of Arizona  Tucson AZ 85724 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,6,25]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2015.06.006"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2005.11.007"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.23242"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22180"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.2147\/CIA.S115472"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2014.12.010"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2019.01.015"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1011513223894"},{"key":"e_1_2_7_9_1","first-page":"1","volume":"79","author":"Clarke T. 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