title: Arthritis induces lymphocytic bone marrow inflammation and endosteal bone formation.
abstract: Arthritis can destroy the cortical bone barrier and expose bone marrow to synovial tissue. This study examines bone marrow changes in arthritis and its effects on cortical bone remodeling. Bone marrow next to arthritic lesions exhibits B-lymphocyte-rich infiltrates, which express BMPs and stimulate endosteal bone formation. Thus, bone marrow actively participates in the arthritic process.
  
  
  BACKGROUND
  Imaging studies have shown that bone marrow changes occur in patients with rheumatoid arthritis (RA). To examine whether bone marrow is affected during arthritis, human TNF transgenic (hTNFtg) mice, which constitute an established animal model of human RA, were examined for bone marrow changes.
  
  
  METHODS
  The hind paws (tarsal area) of 22 untreated hTNFtg mice, 5 hTNFtg mice treated with anti-TNF (infliximab), and 5 wildtype (WT) mice were examined histologically, immunohistochemically, and by means of mRNA in situ hybridization.
  
  
  CONCLUSIONS
  All untreated hTNFtg mice with moderate (n = 10) and severe (n = 7) disease developed inflammatory bone marrow lesions during the course of disease, whereas no such lesions appeared in hTNFtg mice with mild disease (n = 5) and WT mice. Bone marrow infiltrates were almost exclusively composed of lymphocytes, and the overwhelming proportion (>80%) was B-cells. Presence and extent of bone marrow infiltrates were closely linked to severity of arthritis. In addition, blockade of TNF effectively reduced bone marrow inflammation. Interestingly, osteoblast numbers were increased at the endosteal surface in the vicinity of these lesions. Moreover, osteoid deposition; expression of bone matrix proteins, such as osteocalcin and osteopontin; and mineralization were enhanced, suggesting that inflammatory bone marrow infiltrates induce bone formation. Indeed, B-lymphocytes of these lesions expressed bone morphogenetic protein (BMP)-6 and -7, which are important stimulators of new bone formation. Thus, we conclude that bone marrow actively participates in destructive arthritis by generating B-lymphocyte-rich bone marrow lesions and inducing endosteal bone formation.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine III, University of Vienna, Vienna, Austria.
authors.forename: Birgit
authors.initials: B
authors.lastname: Görtz
authors.forename: Silvia
authors.initials: S
authors.lastname: Hayer
authors.forename: Kurt
authors.initials: K
authors.lastname: Redlich
authors.forename: Jochen
authors.initials: J
authors.lastname: Zwerina
authors.forename: Makyieh
authors.initials: M
authors.lastname: Tohidast-Akrad
authors.forename: Birgit
authors.initials: B
authors.lastname: Tuerk
authors.forename: Christine
authors.initials: C
authors.lastname: Hartmann
authors.forename: George
authors.initials: G
authors.lastname: Kollias
authors.forename: Günter
authors.initials: G
authors.lastname: Steiner
authors.forename: Josef S
authors.initials: JS
authors.lastname: Smolen
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000473:pathology*; D001402:B-Lymphocytes / Q000473:pathology*; D001853:Bone Marrow / Q000473:pathology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D014409:Tumor Necrosis Factor-alpha