title: Selenoproteins and selenium status in bone physiology and pathology.
abstract: BACKGROUND
  Emerging evidence supports the view that selenoproteins are essential for maintaining bone health.
  
  
  METHODS
  The current state of knowledge concerning selenoproteins and Se status in bone physiology and pathology is summarized.
  
  
  CONCLUSIONS
  Antioxidant selenoproteins including glutathione peroxidase (GPx) and thioredoxin reductase (TrxR), as a whole, play a pivotal role in maintaining bone homeostasis and protecting against bone loss. GPx1, a major antioxidant enzyme in osteoclasts, is up-regulated by estrogen, an endogenous inhibitor of osteoclastogenesis. TrxR1 is an immediate early gene in response to 1α,25-dihydroxyvitamin D3, an osteoblastic differentiation agent. The combination of 1α,25-dihydroxyvitamin D3 and Se generates a synergistic elevation of TrxR activity in Se-deficient osteoblasts. Of particular concern, pleiotropic TrxR1 is implicated in promoting NFκB activation. Coincidentally, TrxR inhibitors such as curcumin and gold compounds exhibit potent osteoclastogenesis inhibitory activity. Studies in patients with the mutations of selenocysteine insertion sequence-binding protein 2, a key trans-acting factor for the co-translational insertion of selenocysteine into selenoproteins have clearly established a causal link of selenoproteins in bone development. Se transport to bone relies on selenoprotein P. Plasma selenoprotein P concentrations have been found to be positively correlated with bone mineral density in elderly women.
  
  
  CONCLUSIONS
  A full understanding of the role and function of selenoproteins and Se status on bone physiology and pathology may lead to effectively prevent against or modify bone diseases by using Se.
authors.affiliation: Department of Orthopaedic Oncology, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, PR China.
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: School of Tea Food Science, Anhui Agricultural University, Hefei 230036, Anhui, PR China. Electronic address: zjs@ahau.edu.cn.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedic Oncology, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, PR China. Electronic address: jianruxiao83@163.com.
authors.forename: Jianru
authors.initials: J
authors.lastname: Xiao
keywords: Bone; Osteoblast; Osteoclast; Selenium; Selenoprotein