Osteoblasts from the sclerotic subchondral bone downregulate aggrecan but upregulate metalloproteinases expression by chondrocytes. This effect is mimicked by interleukin-6, -1beta and oncostatin M pre-treated non-sclerotic osteoblasts.
OBJECTIVE
To determine the effects of osteoarthritic (OA) subchondral osteoblasts on the metabolism of human OA chondrocytes in alginate beads.


METHODS
Human chondrocytes were isolated from OA cartilage and cultured in alginate beads for 4 days in the absence or in the presence of osteoblasts isolated from non-sclerotic (N) or sclerotic (SC) zones of human OA subchondral bone in monolayer (co-culture system). Before co-culture, osteoblasts were incubated for 72 h with or without 1.7ng/ml interleukin (IL)-1beta, 100 ng/ml IL-6 with its soluble receptor (50 ng/ml) or 10 ng/ml oncostatin M (OSM). Aggrecan (AGG) and matrix metalloproteases (MMP)-3 and -13 mRNA levels in chondrocytes were quantified by real-time polymerase chain reaction. AGG production was assayed by a specific enzyme amplified sensitivity immunoassay.


RESULTS
SC, but not N, osteoblasts induced a significant inhibition of AGG production and AGG gene expression by human OA chondrocytes in alginate beads, and significantly increased MMP-3 and MMP-13 gene expression by chondrocytes. When they were pre-incubated with IL-1beta, IL-6 or OSM, N osteoblasts inhibited AGG synthesis and increased MMP-3 and -13 gene expression by chondrocytes in alginate beads in a same order of magnitude as SC osteoblasts.


CONCLUSIONS
These results demonstrate that SC OA subchondral osteoblasts could contribute to cartilage degradation by stimulating chondrocytes to produce more MMP and also by inhibiting AGG synthesis.
Sanchez
C
C
Bone and Cartilage Metabolism Research Unit, Institute of Pathology B23, University Hospital, Sart-Tilman, 4000 Liège, Belgium.
Deberg
M A
MA
Piccardi
N
N
Msika
P
P
Reginster
J-Y L
JY
Henrotin
Y E
YE
D000368:Aged; D053674:Aggrecans; D002102:Cadaver; D019902:Chondrocytes / Q000276:immunology / Q000378:metabolism*; D018920:Coculture Techniques; D017364:Collagenases / Q000032:analysis; D015536:Down-Regulation / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000032:analysis*; D005269:Femur; D015870:Gene Expression / Q000502:physiology; D006131:Growth Inhibitors / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D037181:Lectins, C-Type / Q000032:analysis*; D008297:Male; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3 / Q000032:analysis; D045726:Metalloproteases / Q000032:analysis*; D008875:Middle Aged; D053683:Oncostatin M; D020370:Osteoarthritis, Knee / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism*; D010455:Peptides / Q000276:immunology; D010641:Phenotype; D011509:Proteoglycans / Q000032:analysis*; D012598:Sclerosis; D013977:Tibia; D015854:Up-Regulation / Q000502:physiology
D053674:Aggrecans; D016326:Extracellular Matrix Proteins; D006131:Growth Inhibitors; D007375:Interleukin-1; D015850:Interleukin-6; D037181:Lectins, C-Type; C508351:OSM protein, human; D010455:Peptides; D011509:Proteoglycans; D053683:Oncostatin M; D045726:Metalloproteases; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3