Relationship between inflammation, bone destruction, and osteoproliferation in the HLA-B27/human β2 -microglobulin-transgenic rat model of spondylarthritis.
OBJECTIVE
Inhibition of inflammation and destruction, but not of osteoproliferation, in patients with spondylarthritis (SpA) treated with anti-tumor necrosis factor raises the question of how these three processes are interrelated. This study was undertaken to analyze this relationship in a rat model of SpA.


METHODS
Histologic spine and joint samples from HLA-B27/human β(2) -microglobulin (hβ(2) m)-transgenic rats were analyzed for signs of spondylitis and destructive arthritis and semiquantitatively scored as showing mild, moderate, or severe inflammation.


RESULTS
In rats exhibiting spondylitis, mildly inflamed sections displayed lymphocyte infiltration in connective tissue adjacent to the junction of the anulus fibrosus and vertebral bone but not at the enthesis. Moderately inflamed tissue samples contained osteoclasts eroding bone outside the cartilage end plate. In sections from rats with severe inflammation, the cartilage end plate and underlying bone marrow were also affected. End-stage disease was characterized by complete destruction of the intervertebral disc and vertebrae, with ongoing infiltration. Osteoproliferation was not observed in samples from rats with no or mild inflammation, but was present at the edge of the vertebrae in sections with moderate inflammation and persisted during severe inflammation and end-stage destruction. Osteoproliferation occurred at the border of inflammation, at a distance from bone destruction. A strong correlation between the extent of inflammation, destruction, and osteoproliferation was observed. Sections from rats with arthritis displayed a similar pattern of synovial inflammation associated with bone destruction, and simultaneous but topographically distinct osteoproliferation starting from the periosteum.


CONCLUSIONS
SpA in B27/hβ(2) m-transgenic rats is characterized by destructive inflammatory pannus tissue rather than by enthesitis or osteitis. Destruction and osteoproliferation occur simultaneously but at distinct sites in joints with moderate to severe inflammation.
Academic Medical Center and University of Amsterdam, Amsterdam, The Netherlands. l.m.vanduivenvoorde@amc.uva.nl
Leonie M
LM
van Duivenvoorde
Martha L
ML
Dorris
Nimman
N
Satumtira
Melissa N
MN
van Tok
Kurt
K
Redlich
Paul P
PP
Tak
Joel D
JD
Taurog
Dominique L
DL
Baeten
D000818:Animals; D001842:Bone and Bones / Q000276:immunology / Q000473:pathology*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D015796:HLA-B27 Antigen / Q000235:genetics* / Q000276:immunology; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D007596:Joints / Q000276:immunology / Q000473:pathology*; D010010:Osteoclasts / Q000276:immunology / Q000473:pathology; D051381:Rats; D055647:Rats, Transgenic; D025241:Spondylarthritis / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D001613:beta 2-Microglobulin / Q000235:genetics / Q000276:immunology
D015796:HLA-B27 Antigen; D001613:beta 2-Microglobulin