The c-maf gene expression profile was investigated in normal and osteoarthritic articular cartilage using in situ hybridization, qualitative reverse transcription-polymerase chain reaction (RT-PCR) and quantitative real-time RT-PCR. Osteoarthritic samples were obtained from 10 patients undergoing total knee replacement for severe osteoarthritis of the knee joints, and control samples from 10 trauma patients undergoing amputation. Expression of c-maf was significantly upregulated in osteoarthritic cartilage compared with normal cartilage. Using in situ hybridization, distribution of a specific c-maf mRNA signal was found in the top zone and a decreased signal was found in the lower middle zone and the deep zone in osteoarthritic cartilage. A prominent c-maf mRNA signal was seen particularly in proliferating ‘chondrocyte clusters’. In contrast, in normal cartilage almost no c-maf-positive cells were found. These findings suggest that c-maf may be important in chondrocyte hypertrophy and terminal differentiation, and may be involved in the pathogenesis of osteoarthritis.
Martel-PelletierJ: Pathophysiology of osteoarthritis. Osteoarthritis Cartilage2004; 12 (suppl A): S31–S33.
2.
PulligOWeselohGRonnebergerD: Chondrocyte differentiation in human osteoarthritis: Expression of osteocalcin in normal and osteoarthritic cartilage and bone. Calcif Tissue Int2000; 67: 230–240.
3.
DrissiHZuscikMRosierR: Transcriptional regulation of chondrocyte maturation: Potential involvement of transcription factors in OA pathogenesis. Mol Aspects Med2005; 26: 169–179.
4.
TchetinaEVAntoniouJTanzerM: Transforming growth factor-β2 suppresses collagen cleavage in cultured human osteoarthritic cartilage, reduces expression of genes associated with chondrocyte hypertrophy and degradation, and increases prostaglandin E2 production. Am J Pathol2006; 168: 131–140.
5.
KataokaKNishizawaMKawaiS: Structure–function analysis of the maf oncogene product, a member of the b-Zip protein family. J Virol1993; 67: 2133–2141.
6.
NishizawaMKataokaKGotoN: v-maf, a viral oncogene that encodes a ‘leucine zipper’ motif. Proc Natl Acad Sci USA1989; 86: 7711–7715.
7.
ChesiMBergsagelPLShonukanOO: Frequent dysregulation of the c-maf protooncogene at 16q23 by translocation to an Ig locus in multiple myeloma. Blood1998; 91: 4457–4463.
8.
GiudicelliFGilardi-HebenstreitPMechta-GrigoriouF: Novel activities of Mafb underlie its dual role in hindbrain segmentation and regional specification. Dev Biol2003; 253: 150–162.
9.
FrancastelCPoindessous-JazatVAugery-BourgetY: NF-E2p18/mafK is required in DMSO-induced differentiation of Friend erythroleukemia cells by enhancing NF-E2 activity. Leukemia1997; 11: 273–280.
10.
ChenXPFalknerDHMorelPA: Impaired IL-4 production by CD8+ T cells in NOD mice is related to a defect of c-Maf binding to the IL-4 promoter. Eur J Immunol2005; 35: 1408–1417.
11.
OginoHYasudaK: Induction of lens differentiation by activation of a bZIP transcription factor, L-Maf. Science1998; 280: 115–118.
12.
MacLeanHEKimJIGlimcherMJ: Absence of transcription factor c-maf causes abnormal terminal differentiation of hypertrophic chondrocytes during endochondral bone development. Dev Biol2003; 262: 51–63.
13.
ThomasCMFullerCJWhittlesCE: Chondrocyte death by apoptosis is associated with cartilage matrix degradation. Osteoarthritis Cartilage2007; 15: 27–34.
14.
KirschTSwobodaBNahH: Activation of annexin II and V expression, terminal differentiation, mineralization and apoptosis in human osteoarthritic cartilage. Osteoarthritis Cartilage2000; 8: 294–302.
15.
von der MarkKKirschTNerlichA: Type X collagen synthesis in human osteoarthritic cartilage. Indication of chondrocyte hypertrophy. Arthritis Rheum1992; 35: 806–811.
16.
D'AngeloMYanZNooreyazdanM: MMP-13 is induced during chondrocyte hypertrophy. J Cell Biochem2000; 77: 678–693.
17.
AignerTStössHWeselohG: Activation of collagen type II expression in osteoarthritic and rheumatoid cartilage. Virchows Arch B Cell Pathol Incl Mol Pathol1992; 62: 337–345.
18.
HambachLNeureiterDZeilerG: Severe disturbance of the distribution and expression of type VI collagen chains in osteoarthritic articular cartilage. Arthritis Rheum1998; 41: 986–996.
19.
BillinghurstRCDahlbergLIonescuM: Enhanced cleavage of type II collagen by collagenases in osteoarthritic articular cartilage. J Clin Invest1997; 99: 1534–1545.
20.
LefebvreVHuangWHarleyVR: SOX9 is a potent activator of the chondrocyte-specific enhancer of the pro α1(II) collagen gene. Mol Cell Biol1997; 17: 2336–2346.
21.
HuangWLuNEberspaecherH: A new long form of c-Maf cooperates with Sox9 to activate the type II collagen gene. J Biol Chem2002; 277: 50668–50675.
22.
YatsugiNTsukazakiTOsakiM: Apoptosis of articular chondrocytes in rheumatoid arthritis and osteoarthritis: Correlation of apoptosis with degree of cartilage destruction and expression of apoptosis-related proteins of p53 and c-myc. J Orthop Sci2000; 5: 150–156.
23.
PengSLalaniSLeavenworthJW: c-Maf interacts with c-Myb to down-regulate Bcl-2 expression and increase apoptosis in peripheral CD4 cells. Eur J Immunol2007; 37: 2868–2880.
