Proinflammatory cytokines and chemokine production and expression by human osteoblasts isolated from patients with rheumatoid arthritis and osteoarthritis.
OBJECTIVE
To evaluate whether subchondral osteoblasts (OB) are involved in the production of cytokines and chemokines in rheumatic diseases.


METHODS
OB were isolated from subchondral bone of rheumatoid arthritis (RA), osteoarthritis (OA) and post-traumatic (PT) patients, cultured in vitro in the presence or absence of interleukin 1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), and assessed for the production, immunolocalization, and mRNA expression of proinflammatory cytokines (IL-1alpha, IL-1beta, TNF-alpha) and alpha and beta chemokines [IL-8, growth related gene product (GRO-alpha), monocyte chemoattractant protein 1 (MCP-1), RANTES, and macrophage inflammatory proteins MIP-1alpha, MIP-1beta].


RESULTS
Cultured OB from different patients did not release IL-1alpha, IL-1beta, or TNF-alpha, and constitutively secreted IL-8, GRO-alpha, and MCP-1, while RANTES, MIP-1alpha, MIP-1beta were undetectable or near the lower level of sensitivity of the immunoenzymatic assay. GRO-alpha was significantly higher in RA than in OA and PT patients. IL-1beta and TNF-alpha alone or in combination strongly stimulated chemokine release by OB. Only RANTES production was not increased by the combination of the 2 cytokines. IL-1alpha, IL-1beta, and TNF-alpha were expressed as cytoplasmic proteins and were not secreted by OB even after stimulation.


CONCLUSIONS
OB from subchondral bone release chemokines that could be involved in the mechanisms that directly or indirectly cause bone remodelling and cartilage destruction.
Lisignoli
G
G
Laboratorio di Immunologia e Genetica, IV Divisione, Istituto Ortopedici Rizzoli, Bologna, Italy.
Toneguzzi
S
S
Pozzi
C
C
Piacentini
A
A
Riccio
M
M
Ferruzzi
A
A
Gualtieri
G
G
Facchini
A
A
D000368:Aged; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D019644:Arthroplasty, Replacement, Hip; D015415:Biomarkers / Q000032:analysis; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D017931:DNA Primers / Q000737:chemistry; D004357:Drug Synergism; D005260:Female; D005270:Femur Head / Q000293:injuries / Q000378:metabolism / Q000601:surgery; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D012313:RNA / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines; D017931:DNA Primers; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D012313:RNA