Angiogenesis and nerve growth factor at the osteochondral junction in rheumatoid arthritis and osteoarthritis.
Objectives. The osteochondral junction can be a source of pain in both RA and OA. Growth of blood vessels and nerves from the subchondral bone into articular cartilage may mediate the association between joint pathology and symptoms. We have investigated associations between angiogenesis, inflammation and neurovascular growth factor expression at the osteochondral junction in human arthritis. Methods. Osteochondral junctions from medial tibial plateaux of patients undergoing arthroplasty for RA (n = 10) or OA (n = 11), or from non-arthritic post-mortem controls (n = 11) were characterized by immunohistochemistry for CD34 and smooth muscle α-actin (blood vessels), CD68 (macrophages), CD3 (lymphocytes), proliferating cell nuclear antigen, vascular endothelial, platelet-derived and nerve growth factor (NGF). Results. Osteochondral angiogenesis was demonstrated as increased endothelial cell proliferation and vascular density in non-calcified articular cartilage, both in RA and OA. Osteochondral angiogenesis was associated with subchondral bone marrow replacement by fibrovascular tissue expressing VEGF, and with increased NGF expression within vascular channels. RA was characterized by greater lymphocyte infiltration and PDGF expression than OA, whereas chondrocyte expression of VEGF was a particular feature of OA. NGF was observed in vascular channels that contained calcitonin gene-related peptide-immunoreactive sensory nerve fibres. Conclusions. Osteochondral angiogenesis in RA and OA is associated with growth factor expression by cells within subchondral spaces, vascular channels and by chondrocytes. NGF expression and sensory nerve growth may link osteochondral angiogenesis to pain in arthritis.
Walsh
David A
DA
Arthritis Research UK Pain Centre, Division of Academic Rheumatology, University of Nottingham, Clinical Sciences Building, Nottingham City Hospital, Nottingham, UK. david.walsh@nottingham.ac.uk
McWilliams
Dan F
DF
Turley
Matthew J
MJ
Dixon
Madeleine R
MR
Fransès
Rebecca E
RE
Mapp
Paul I
PI
Wilson
Deborah
D
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D002358:Cartilage, Articular / Q000378:metabolism; D005260:Female; D006801:Humans; D007719:Knee Joint / Q000098:blood supply; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D020932:Nerve Growth Factor / Q000378:metabolism*; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D013223:Statistics as Topic; D013583:Synovial Membrane
D020932:Nerve Growth Factor