title: (-)-Epigallocatechin-3-gallate improves bone microarchitecture in ovariectomized rats.
abstract: OBJECTIVE
  Previously, we reported that (-)-epigallocatechin-3-gallate (EGCG), a green tea polyphenol, increased the osteogenic differentiation of murine bone marrow mesenchymal stem cells by increasing the messenger RNA expression of osteogenesis-related genes, alkaline phosphatase activity, and, eventually, mineralization. The present study further investigated the effects of EGCG on bone microstructure change and possible mechanisms in ovariectomy (OVX)-induced osteopenic rats.
  
  
  METHODS
  Rats subjected to OVX were administered EGCG systemically for 12 weeks. Proximal tibial bone mineral densities before and after treatment were compared between groups. Changes in the microarchitecture of both the proximal tibia and the third lumbar spine were compared between EGCG-treated and nontreated groups using micro-CT (μCT). Bone histology and immunohistochemistry in the proximal tibia were evaluated.
  
  
  RESULTS
  Results showed that EGCG 3.4 mg/kg/day (estimated peak serum concentration, 10 μmol/L) hampered the decrease in bone mineral density (from 7.97% to 3.96%) and improved the parameters of μCT measurements, including bone volume (from 18% to 27%), trabecular thickness (from 0.17 to 0.22 mm), trabecular number (from 1.13 to 1.37 mm(-1)), and trabecular separation (from 0.91 to 0.69 mm), compared with nontreated ovariectomized rats. Similar improvements in bone volume (from 30% to 49%) and trabecular thickness (from 0.14 to 0.26 mm) were also found in the third lumbar spine. Bone volume in the tibial cortex also increased after EGCG treatment (from 9% to 28%). A higher trabecular number and greater trabecular volume were also seen in histology, further confirming the results of μCT. The immunolocalized bone morphogenetic protein 2 brown-stained area increased from 31% in the OVX group to 53% in the OVX + 10 EGCG group (P < 0.01). Serial biochemistry data revealed no significant systemic toxic effect of EGCG.
  
  
  CONCLUSIONS
  Intraperitoneal treatment with EGCG 3.4 mg/kg/day for 3 months can mitigate bone loss and improve bone microarchitecture in ovariectomized rats, and increased expression of bone morphogenetic protein 2 may contribute to this effect.
authors.affiliation: Department of Orthopedics, College of Medicine, Faculty of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chung-Hwan
authors.initials: CH
authors.lastname: Chen
authors.forename: Lin
authors.initials: L
authors.lastname: Kang
authors.forename: Ru-Wei
authors.initials: RW
authors.lastname: Lin
authors.forename: Yin-Chih
authors.initials: YC
authors.lastname: Fu
authors.forename: Yi-Shan
authors.initials: YS
authors.lastname: Lin
authors.forename: Je-Ken
authors.initials: JK
authors.lastname: Chang
authors.forename: Hui-Ting
authors.initials: HT
authors.lastname: Chen
authors.forename: Chia-Hsin
authors.initials: CH
authors.lastname: Chen
authors.forename: Sung-Yen
authors.initials: SY
authors.lastname: Lin
authors.forename: Gwo-Jaw
authors.initials: GJ
authors.lastname: Wang
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Ho
mesh_terms: D000818:Animals; D001835:Body Weight; D015519:Bone Density / Q000187:drug effects; D001851:Bone Diseases, Metabolic / Q000473:pathology / Q000517:prevention & control*; D055396:Bone Morphogenetic Protein 2 / Q000032:analysis; D001842:Bone and Bones / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000473:pathology; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000187:drug effects / Q000473:pathology
chemical_list: D055396:Bone Morphogenetic Protein 2; D002392:Catechin; C045651:epigallocatechin gallate