title: Inflammation in arthritis induces expression of BMP3, an inhibitor of bone formation.
abstract: OBJECTIVE
  Inflammation in diseases such as rheumatoid arthritis (RA) stimulates osteoclast-mediated articular bone erosion and inhibits osteoblast-mediated bone formation, leading to a net loss of bone. Pro-inflammatory cytokines and antagonists of the Wnt signalling pathway have been implicated in the inhibition of osteoblast differentiation and activity in RA, contributing to the erosive process and impairing erosion healing. Importantly, osteoblast differentiation and function are also regulated by the osteogenic bone morphogenetic protein (BMP) signalling pathway, which is antagonized by BMP3. We therefore examined the potential role of BMP3 in inflammatory arthritis.
  
  
  METHODS
  Two murine models of RA, K/BxN serum transfer arthritis (STA) and antigen-induced arthritis (AIA), were used to establish the temporal expression of BMP3 and the cellular sources of BMP3 mRNA and protein in inflammatory arthritis. To determine the effects of inflammation on the expression of BMP3 in osteoblasts, murine calvarial osteoblasts were treated with pro-inflammatory cytokines and BMP3 expression was assessed.
  
  
  RESULTS
  In both murine models of RA, BMP3 mRNA and protein are highly expressed by osteoblasts lining inflammation-bone interfaces late in the course of arthritis. Synovial tissues are not a significant source of BMP3. BMP3 expression is induced in osteocalcin-expressing osteoblasts in vitro following stimulation by tumour necrosis factor (TNF).
  
  
  CONCLUSIONS
  These data implicate BMP3 as a novel factor that may act locally to contribute to the erosive process and inhibit the repair of articular bone in RA through inhibition of osteoblast differentiation and function.
authors.affiliation: a Department of Medicine , University of Massachusetts Medical School , Worcester , MA , USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Matzelle
authors.affiliation: a Department of Medicine , University of Massachusetts Medical School , Worcester , MA , USA.
authors.forename: A T
authors.initials: AT
authors.lastname: Shaw
authors.affiliation: a Department of Medicine , University of Massachusetts Medical School , Worcester , MA , USA.
authors.forename: R
authors.initials: R
authors.lastname: Baum
authors.affiliation: a Department of Medicine , University of Massachusetts Medical School , Worcester , MA , USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Maeda
authors.affiliation: a Department of Medicine , University of Massachusetts Medical School , Worcester , MA , USA.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: a Department of Medicine , University of Massachusetts Medical School , Worcester , MA , USA.
authors.forename: S
authors.initials: S
authors.lastname: Karmakar
authors.affiliation: a Department of Medicine , University of Massachusetts Medical School , Worcester , MA , USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Manning
authors.affiliation: b Murdoch Childrens Research Institute , Parkville , Victoria , Australia.
authors.forename: N C
authors.initials: NC
authors.lastname: Walsh
authors.affiliation: c Department of Developmental Biology , Harvard School of Dental Medicine , Boston , MA , USA.
authors.forename: V
authors.initials: V
authors.lastname: Rosen
authors.affiliation: a Department of Medicine , University of Massachusetts Medical School , Worcester , MA , USA.
authors.forename: E M
authors.initials: EM
authors.lastname: Gravallese
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D055398:Bone Morphogenetic Protein 3 / Q000235:genetics* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012886:Skull / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C525758:Bmp3 protein, mouse; D055398:Bone Morphogenetic Protein 3; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha