title: Omentin-1 exerts bone-sparing effect in ovariectomized mice.
abstract: Omentin-1 inhibited osteoblast differentiation in vitro. In co-culture systems of osteoblasts and osteoclast precursors, omentin-1 reduced osteoclast formation by stimulating osteoprotegerin (OPG) and inhibiting receptor activator for nuclear factor κB ligand (RANKL) production in osteoblasts. In vivo, adenovirus-mediated overexpression of omentin-1 suppressed bone turnover and restored bone mineral density (BMD) and bone strength in ovariectomized mice.
  
  
  BACKGROUND
  Omentin-1 (also intelectin-1) is a recently identified visceral adipose tissue-derived cytokine that is highly abundant in plasma. This study was undertaken to investigate the effects of omentin-1 on bone metabolism.
  
  
  METHODS
  Osteoblast differentiation was assessed by measuring alkaline phosphatase activity, osteocalcin production and matrix mineralization. OPG and RANKL protein expression and secretion in osteoblasts were detected by Western blot and ELISA, respectively. The effect of recombinant omentin-1 on osteoclast formation was examined in co-culture systems of osteoblasts and osteoclast precursors. The effects of intravenous administration of adenoviral-delivered omentin-1 on bone mass, bone strength, and bone turnover were also examined in ovariectomized mice.
  
  
  RESULTS
  In vitro, omentin-1 inhibited osteoblast differentiation, while it had no direct effect on osteoclast differentiation; it also reduced osteoclast formation in the co-culture systems through stimulating OPG and inhibiting RANKL production in osteoblasts. In vivo, adenovirus-mediated overexpression of omentin-1 partially restored BMD and bone strength in ovariectomized mice, accompanied by decreased levels of plasma osteocalcin and tartrate-resistant acid phosphatase-5b and lower serum RANKL/OPG ratios.
  
  
  CONCLUSIONS
  The present study suggests that omentin-1 ameliorates bone loss induced by estrogen deficiency via downregulating the RANKL/OPG ratio.
authors.affiliation: Institute of Endocrinology and Metabolism, Second Xiangya Hospital of Central South University, 139# Middle Renmin Road, Changsha, Hunan 410011, People's Republic of China.
authors.forename: H
authors.initials: H
authors.lastname: Xie
authors.forename: P-L
authors.initials: PL
authors.lastname: Xie
authors.forename: X-H
authors.initials: XH
authors.lastname: Luo
authors.forename: X-P
authors.initials: XP
authors.lastname: Wu
authors.forename: H-D
authors.initials: HD
authors.lastname: Zhou
authors.forename: S-Y
authors.initials: SY
authors.lastname: Tang
authors.forename: E-Y
authors.initials: EY
authors.lastname: Liao
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D016723:Bone Remodeling / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D037102:Lectins / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects; D010024:Osteoporosis / Q000097:blood / Q000503:physiopathology / Q000628:therapy*; D053244:Osteoprotegerin / Q000097:blood; D010052:Ovariectomy; D053245:RANK Ligand / Q000097:blood; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D016207:Cytokines; D058851:GPI-Linked Proteins; C432397:ITLN1 protein, human; D037102:Lectins; D053244:Osteoprotegerin; D053245:RANK Ligand; D011994:Recombinant Proteins; D000469:Alkaline Phosphatase