B-cell infiltrates induce endosteal bone formation in inflammatory arthritis.
The objective of this study was to investigate the function of inflammatory bone marrow infiltrates found in vicinity to joints affected by inflammatory arthritis. These bone marrow infiltrates are rich in B cells and emerge at the interphase between bone marrow and synovial inflammatory tissue, where cortical bone has been broken. We deleted an essential molecule of B-cell development, Brutońs tyrosine kinase (Btk), in arthritic TNF-transgenic mice and studied its effect on bone marrow inflammation. Although antigen responses, immunoglobulin levels, and autoantibody production were diminished in Btk(-/-)hTNFtg mice, synovial inflammation developed normally. However, bone marrow infiltrates were significantly diminished in Btk(-/-)hTNFtg mice, which lead to impaired bone formation at endosteal sites underneath bone erosions and an increased invasion of synovial inflammatory cells into the bone marrow. Expression of bone morphogenic protein-7 was dramatically decreased in Btk(-/-)hTNFtg mice. These results do not only indicate that bone formation at endosteal regions next to bone marrow infiltrates is driven by B cells but also show that bone marrow aggregates in the vicinity of inflamed joint appear as an attempt to counter the invasion of inflammatory tissue into the bone marrow.
Hayer
Silvia
S
Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
Polzer
Karin
K
Brandl
Andreas
A
Zwerina
Jochen
J
Kireva
Trayana
T
Smolen
Josef S
JS
Schett
Georg
G
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000473:pathology*; D001402:B-Lymphocytes / Q000473:pathology*; D001483:Base Sequence; D001846:Bone Development; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction
D017931:DNA Primers