title: Effects of Resveratrol Supplementation on  Methotrexate Chemotherapy-Induced Bone Loss.
abstract: Intensive cancer chemotherapy is known to cause bone defects, which currently lack treatments. This study investigated the effects of polyphenol resveratrol (RES) in preventing bone defects in rats caused by methotrexate (MTX), a commonly used antimetabolite in childhood oncology. Young rats received five daily MTX injections at 0.75 mg/kg/day. RES was orally gavaged daily for seven days prior to, and during, five-day MTX administration. MTX reduced growth plate thickness, primary spongiosa height, trabecular bone volume, increased marrow adipocyte density, and increased mRNA expression of the osteogenic, adipogenic, and osteoclastogenic factors in the tibial bone. RES at 10 mg/kg was found not to affect bone health in normal rats, but to aggravate the bone damage in MTX-treated rats. However, RES supplementation at 1 mg/kg preserved the growth plate, primary spongiosa, bone volume, and lowered the adipocyte density. It maintained expression of genes involved in osteogenesis and decreased expression of adipogenic and osteoclastogenic factors. RES suppressed osteoclast formation ex vivo of bone marrow cells from the treated rats. These data suggest that MTX can enhance osteoclast and adipocyte formation and cause bone loss, and that RES supplementation at 1 mg/kg may potentially prevent these bone defects.
authors.affiliation: Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide SA 5001, Australia. alice.lee@unisa.edu.au.
authors.forename: Alice M C
authors.initials: AM
authors.lastname: Lee
authors.affiliation: Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide SA 5001, Australia. tetyanas@geneworks.com.au.
authors.forename: Tetyana
authors.initials: T
authors.lastname: Shandala
authors.affiliation: Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide SA 5001, Australia. soopp001@students.unisa.edu.au.
authors.forename: Pei Pei
authors.initials: PP
authors.lastname: Soo
authors.affiliation: Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide SA 5001, Australia. wen.su@unisa.edu.au.
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Su
authors.affiliation: Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide SA 5001, Australia. tristan.king@unisa.edu.au.
authors.forename: Tristan J
authors.initials: TJ
authors.lastname: King
authors.affiliation: Institute of Orthopaedics, Lanzhou General Hospital, Lanzhou Command of People's Liberation Army, Lanzhou 730050, China. chenkm@lut.cn.
authors.forename: Ke-Ming
authors.initials: KM
authors.lastname: Chen
authors.affiliation: Clinical Nutrition Research Centre, University of Newcastle, Callaghan NSW 2308, Australia. peter.howe@newcastle.edu.au.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Howe
authors.affiliation: Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide SA 5001, Australia. cory.xian@unisa.edu.au.
authors.forename: Cory J
authors.initials: CJ
authors.lastname: Xian
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D001847:Bone Diseases / Q000139:chemically induced / Q000188:drug therapy*; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects*; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage*
chemical_list: D012333:RNA, Messenger; D013267:Stilbenes; D000077185:Resveratrol; D008727:Methotrexate
keywords: resveratrol;   bone growth arrest;  adipocytes;  bone loss;  bone marrow adiposity;  cancer chemotherapy;  growth plate;  methotrexate;  osteoblasts;  osteoclasts