{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T23:38:40Z","timestamp":1790638720117,"version":"4.1.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2017,10,30]],"date-time":"2017-10-30T00:00:00Z","timestamp":1509321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K08 AR067854, R01 AR061376, R01 EB017274, and P30 AR061313"],"award-info":[{"award-number":["K08 AR067854, R01 AR061376, R01 EB017274, and P30 AR061313"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,3,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>Osteocytes remodel their surrounding perilacunar matrix and canalicular network to maintain skeletal homeostasis. Perilacunar\/canalicular remodeling is also thought to play a role in determining bone quality. X-linked hypophosphatemia (XLH) is characterized by elevated serum fibroblast growth factor 23 (FGF23) levels, resulting in hypophosphatemia and decreased production of 1,25 dihydroxyvitamin D (1,25D). In addition to rickets and osteomalacia, long bones from mice with XLH (Hyp) have impaired whole-bone biomechanical integrity accompanied by increased osteocyte apoptosis. To address whether perilacunar\/canalicular remodeling is altered in Hyp mice, histomorphometric analyses of tibia and 3D intravital microscopic analyses of calvaria were performed. These studies demonstrate that Hyp mice have larger osteocyte lacunae in both the tibia and calvaria, accompanied by enhanced osteocyte mRNA and protein expression of matrix metalloproteinase 13 (MMP13) and genes classically used by osteoclasts to resorb bone, such as cathepsin K (CTSK). Hyp mice also exhibit impaired canalicular organization, with a decrease in number and branching of canaliculi extending from tibial and calvarial lacunae. To determine whether improving mineral ion and hormone homeostasis attenuates the lacunocanalicular phenotype, Hyp mice were treated with 1,25D or FGF23 blocking antibody (FGF23Ab). Both therapies were shown to decrease osteocyte lacunar size and to improve canalicular organization in tibia and calvaria. 1,25D treatment of Hyp mice normalizes osteocyte expression of MMP13 and classic osteoclast markers, while FGF23Ab decreases expression of MMP13 and selected osteoclast markers. Taken together, these studies point to regulation of perilacunar\/canalicular remodeling by physiologic stimuli including hypophosphatemia and 1,25D. \u00a9 2017 American Society for Bone and Mineral Research.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.3327","type":"journal-article","created":{"date-parts":[[2017,10,30]],"date-time":"2017-10-30T11:05:37Z","timestamp":1509361537000},"page":"499-509","source":"Crossref","is-referenced-by-count":51,"title":["Hormonal Regulation of Osteocyte Perilacunar and Canalicular Remodeling in the Hyp Mouse Model of X-Linked Hypophosphatemia"],"prefix":"10.1093","volume":"33","author":[{"given":"Danielle","family":"Tokarz","sequence":"first","affiliation":[{"name":"Harvard Medical SchoolBostonMAUSA"},{"name":"Advanced Microscopy ProgramCenter for Systems Biology and Wellman Center for PhotomedicineMassachusetts General HospitalBostonMAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janaina S","family":"Martins","sequence":"additional","affiliation":[{"name":"Endocrine UnitMassachusetts General HospitalBostonMAUSA"},{"name":"Harvard Medical SchoolBostonMAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth T","family":"Petit","sequence":"additional","affiliation":[{"name":"Endocrine UnitMassachusetts General HospitalBostonMAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles P","family":"Lin","sequence":"additional","affiliation":[{"name":"Harvard Medical SchoolBostonMAUSA"},{"name":"Advanced Microscopy ProgramCenter for Systems Biology and Wellman Center for PhotomedicineMassachusetts General HospitalBostonMAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie B","family":"Demay","sequence":"additional","affiliation":[{"name":"Endocrine UnitMassachusetts General HospitalBostonMAUSA"},{"name":"Harvard Medical SchoolBostonMAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva 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