Osteoblasts and stromal cells isolated from femora in rheumatoid arthritis (RA) and osteoarthritis (OA) patients express IL-11, leukaemia inhibitory factor and oncostatin M.
We investigated both in vitro and ex vivo the role of mature osteoblasts (OB) and bone marrow stromal cells (BMSC) in RA and OA by analysing the expression of the following IL-6-type cytokines: IL-11, leukaemia inhibitory factor (LIF), oncostatin M (OSM) and IL-6. OB and BMSC were isolated from femora of RA, OA and post-traumatic (PT) patients, cultured in vitro in the presence or absence of IL-1beta and tumour necrosis factor-alpha (TNF-alpha), and assessed for the production and mRNA expression of IL-6-type cytokines. Trabecular bone biopsies were obtained from the inner portions of femoral heads and used for cytokine in situ immunostaining. Cultured OB and BMSC from different patients constitutively secreted IL-11 and IL-6 but not OSM. LIF was secreted only by BMSC, at very low levels. Interestingly, IL-11 basal production was significantly higher in BMSC than in OB in all three groups tested. IL-1beta and TNF-alpha strongly stimulated IL-6-type cytokine release (except for OSM) by both OB and BMSC. OSM was expressed only at mRNA levels in all groups studied. Cytokine immunostaining on bone biopsies confirmed the data obtained on cultured cells: IL-11, IL-6 and LIF proteins were detected both in mesenchymal (BMSC and OB) and mononuclear cells; OSM was found only in mononuclear cells. These data demonstrate that IL-6-type cytokines are constitutively expressed in the bone compartment in RA, OA and PT patients and can be secreted by bone cells at different stages of differentiation (BMSC and OB). This suggests that these cytokines may be involved in the mechanisms of bone remodelling in OA and RA.
Lisignoli
G
G
Laboratorio di Immunologia e Genetica, Instituto di Ricerca Codivilla Putti, Bologna, Italy.
Piacentini
A
A
Toneguzzi
S
S
Grassi
F
F
Cocchini
B
B
Ferruzzi
A
A
Gualtieri
G
G
Facchini
A
A
D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D001706:Biopsy; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005269:Femur / Q000378:metabolism / Q000473:pathology*; D005786:Gene Expression Regulation; D006131:Growth Inhibitors / Q000096:biosynthesis*; D006801:Humans; D017370:Interleukin-11 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000096:biosynthesis*; D008875:Middle Aged; D053683:Oncostatin M; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D010006:Osteoblasts / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology
D016207:Cytokines; D006131:Growth Inhibitors; D017370:Interleukin-11; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; C508351:OSM protein, human; D010455:Peptides; D053683:Oncostatin M