Enhanced expression of interleukin-6, matrix metalloproteinase-13, and receptor activator of NF-kappaB ligand in cells derived from osteoarthritic subchondral bone.
BACKGROUND
The aim of this study was to clarify the significance of subchondral bone in the pathology of osteoarthritis (OA) by investigating the expression of inflammatory cytokines, proteases, and receptor activator of NF-kappaB ligand (RANKL)/receptor activator of NF-kappaB (RANK)/osteoprotegerin (OPG) involved in cartilage degeneration.


METHODS
Subchondral bone was obtained from 19 patients diagnosed with knee OA and 4 patients diagnosed with femoral neck fracture. Subchondral bone osteoblasts (SBOs) were isolated, and total RNA was extracted. Messenger RNA expression of inflammatory cytokines, proteases, and RANKL/RANK/OPG were analyzed using a real-time reverse transcription-polymerase chain reaction (RT-PCR).


RESULTS
Real-time RT-PCR showed that mRNA expressions of interleukin-6 (IL-6), matrix metalloproteinase-13 (MMP-13), and RANKL were significantly enhanced in OA SBOs compared to SBOs without OA. The expressions of these genes was greater in patients with severe cartilage damage than in those with mild cartilage damage. A high correlation between mRNA expression of IL-6 and that of MMP-13 was found in OA SBOs.


CONCLUSIONS
The increases in IL-6, MMP-13, and RANKL expression in OA SBOs suggest that in subchondral bone OA progression involves abnormal osseous tissue remodeling, which induces mechanical property changes. Cartilage degeneration in OA may also be due, at least in part, to IL-6 and MMP-13 produced by SBOs. Comprehensive research on these pathological features may lead to the development of more effective therapies for OA by administration of molecules that affect bone remodeling and metabolism.
Sakao
Kei
K
Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, Japan.
Takahashi
Kenji A
KA
Mazda
Osam
O
Arai
Yuji
Y
Tonomura
Hitoshi
H
Inoue
Atsuo
A
Saito
Masazumi
M
Fujioka
Mikihiro
M
Takamiya
Hisatake
H
Imanishi
Jiro
J
Kubo
Toshikazu
T
D000368:Aged; D000369:Aged, 80 and over; D016723:Bone Remodeling / Q000502:physiology; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D005270:Femur Head / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism*; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
D015850:Interleukin-6; D053245:RANK Ligand; D012333:RNA, Messenger; D053509:Matrix Metalloproteinase 13