title: Effects of Osteochondrin S and select connective tissue ribonucleinate components on human osteoclasts in vitro.
abstract: OBJECTIVE
  Osteochondrin S, a natural product derived from connective tissues and yeast, is used to treat osteoarthritis. The aim of this study was to determine the effect of Osteochondrin S on human osteoclast activity in vitro.
  
  
  METHODS
  Osteoclasts were derived from human peripheral blood mononuclear cells stimulated with macrophage colony-stimulating factor and receptor activator of nuclear factor kappa B (RANK) ligand. Cells were treated with 23.5-587.2 ng/ml Osteochondrin S or 0.2-5 mg/ml of RNA components (synovia, placenta, intervertebral disc or cartilage). The effects on osteoclast formation and resorptive activity were assessed. Real-time polymerase chain reaction was conducted to assess the expression of key osteoclast genes.
  
  
  RESULTS
  Osteochondrin S and the individual RNA extracts resulted in a concentration-dependent inhibition of human osteoclast activity. Osteochondrin S did not affect RANK, nuclear factor of activated T cells (NFATc1), osteoclast-associated receptor or cathepsin K expression. However, there was a significant (P < 0.05) reduction in mRNA expression of calcitonin receptor. Osteochondrin S treatment also significantly increased the expression of osteoclast inhibitory factor interferon-β and, interestingly, increased the expression of tumour necrosis-α-like weak inducer of apoptosis (TWEAK).
  
  
  CONCLUSIONS
  Osteochondrin S inhibited the resorptive ability of osteoclasts. These actions are likely to occur at a late stage during osteoclast formation, downstream of NFATc1. Overall, the findings show that Osteochondrin S inhibition of osteoclast activity may be responsible for its beneficial effects on diseases such as osteoarthritis.
authors.affiliation: Discipline of Anatomy and Pathology, School of Medical Sciences, The University of Adelaide, Adelaide, SA, Australia. melissa.cantley@adelaide.edu.au
authors.forename: Melissa D
authors.initials: MD
authors.lastname: Cantley
authors.forename: K D
authors.initials: KD
authors.lastname: Rainsford
authors.forename: David R
authors.initials: DR
authors.lastname: Haynes
mesh_terms: D018929:Cell Culture Techniques; D002478:Cells, Cultured; D003238:Connective Tissue / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008855:Microscopy, Electron, Scanning; D050778:NFATC Transcription Factors / Q000235:genetics; D009696:Nucleic Acids / Q000494:pharmacology*; D010010:Osteoclasts / Q000187:drug effects* / Q000648:ultrastructure; D053245:RANK Ligand / Q000235:genetics; D012313:RNA / Q000302:isolation & purification / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics; D018003:Receptors, Calcitonin / Q000235:genetics
chemical_list: D050778:NFATC Transcription Factors; C494003:NFATC1 protein, human; D009696:Nucleic Acids; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; D018003:Receptors, Calcitonin; C505686:TNFRSF11A protein, human; C586454:osteochondrin S; D012313:RNA
keywords: Bone resorption; Osteochondrin S; RNA extracts; in-vitro osteoclast assay