Research Article
Hyaluronan oligosaccharide–induced activation of transcription factors in bovine articular chondrocytes
Shigeru Ohno,
Hee-Jeong Im,
Cheryl B. Knudson,
Warren Knudson,
Shigeru Ohno
Rush Medical College, Rush University Medical Center, Chicago, Illinois
Search for more papers by this authorHee-Jeong Im
Rush Medical College, Rush University Medical Center, Chicago, Illinois
Search for more papers by this authorCheryl B. Knudson
Rush Medical College, Rush University Medical Center, Chicago, Illinois
Search for more papers by this authorCorresponding Author
Warren Knudson
Rush Medical College, Rush University Medical Center, Chicago, Illinois
Department of Biochemistry, Rush Medical College, Rush University Medical Center, 1653 West Congress Parkway, Chicago, IL 60612Search for more papers by this authorShigeru Ohno,
Hee-Jeong Im,
Cheryl B. Knudson,
Warren Knudson,
Shigeru Ohno
Rush Medical College, Rush University Medical Center, Chicago, Illinois
Search for more papers by this authorHee-Jeong Im
Rush Medical College, Rush University Medical Center, Chicago, Illinois
Search for more papers by this authorCheryl B. Knudson
Rush Medical College, Rush University Medical Center, Chicago, Illinois
Search for more papers by this authorCorresponding Author
Warren Knudson
Rush Medical College, Rush University Medical Center, Chicago, Illinois
Department of Biochemistry, Rush Medical College, Rush University Medical Center, 1653 West Congress Parkway, Chicago, IL 60612Search for more papers by this authorAbstract
Objective
To document the activity profile of transcription factors following chondrocyte stimulation with hyaluronan (HA) hexasaccharides (HA6) and to determine the expression of genes whose transcriptional activation is tightly associated with the transcription factors.
Methods
Nuclear extracts from bovine articular chondrocytes treated with HA6 were subjected to transcription factor protein–DNA array analysis. Electrophoretic mobility shift assay (EMSA) analyses were performed to confirm the results of protein–DNA array. The gene expressions of matrix metalloproteinase 3 (MMP-3), type II collagen, and cartilage oligomeric matrix protein (COMP) were examined by quantitative real-time reverse transcription–polymerase chain reaction (RT-PCR), and protease activity was assessed by casein zymography.
Results
In the protein–DNA array analysis, 12 transcription factors were up-regulated and 2 transcription factors were down-regulated in the chondrocytes treated with HA6. The transcription factors retinoic acid receptor (RAR), retinoid X receptor (RXR), and Sp-1 exhibited >2-fold increased activity by HA6 treatment, as confirmed by EMSA. RT-PCR analysis showed that the expression levels of MMP-3, type II collagen, and COMP messenger RNA, which are tightly associated with the activation of RAR, RXR, or Sp-1, were up-regulated by treatment with HA6. Addition of high molecular mass HA after HA6 treatment resulted in abrogation of the MMP-3 induction.
Conclusion
These results suggest that HA6 increase the activity of multiple transcription factors in chondrocytes and signal the enhanced expression of key genes involved in cartilage-matrix remodeling and turnover. The data also demonstrate that high molecular mass HA has a potential to suppress the signaling activated by HA6.
REFERENCES
- 1 Hascall VC, Heinegard D. Aggregation of cartilage proteoglycans. II. Oligosaccharide competitors of the proteoglycan-hyaluronic acid interaction. J Biol Chem 1974; 249: 4242–9.
- 2 Knudson CB. Hyaluronan receptor-directed assembly of chondrocyte pericellular matrix. J Cell Biol 1993; 120: 825–34.
- 3 Knudson W, Bartnik E, Knudson CB. Assembly of pericellular matrices by COS-7 cells transfected with CD44 homing receptor genes. Proc Natl Acad Sci U S A 1993; 90: 4003–7.
- 4 Knudson W, Aguiar DJ, Hua Q, Knudson CB. CD44-anchored hyaluronan-rich pericellular matrices: an ultrastructural and biochemical analysis. Exp Cell Res 1996; 228: 216–28.
- 5 Knudson W, Loeser RF. CD44 and integrin matrix receptors participate in cartilage homeostasis. Cell Mol Life Sci 2002; 59: 36–44.
- 6 Knudson W, Casey B, Nishida Y, Eger W, Kuettner KE, Knudson CB. Hyaluronan oligosaccharides perturb cartilage matrix homeostasis and induce chondrocytic chondrolysis. Arthritis Rheum 2000; 43: 1165–74.
- 7 Solursh M, Hardingham TE, Hascall VC, Kimura JH. Separate effects of exogenous hyaluronic acid on proteoglycan synthesis and deposition in pericellular matrix by cultured chick embryo limb chondrocytes. Dev Biol 1980; 75: 121–9.
- 8 Kimura JH, Hardingham TE, Hascall VC, Solursh M. Biosynthesis of proteoglycans and their assembly into aggregates in cultures of chondrocytes from the Swarm rat chondrosarcoma. J Biol Chem 1979; 254: 2600–9.
- 9 Ratcliffe A, Tyler JA, Hardingham TE. Articular cartilage cultured with interleukin 1. Biochem J 1986; 238: 571–80.
- 10 Clements KM, Price JS, Chambers MG, Visco DM, Poole AR, Mason RM. Gene deletion of either interleukin-1β, interleukin-1β–converting enzyme, inducible nitric oxide synthase, or stromelysin 1 accelerates the development of knee osteoarthritis in mice after surgical transection of the medial collateral ligament and partial medial meniscectomy. Arthritis Rheum 2003; 48: 3452–63.
- 11 Chow G, Nietfeld JJ, Knudson CB, Knudson W. Antisense inhibition of chondrocyte CD44 expression leading to cartilage chondrolysis. Arthritis Rheum 1998; 41: 1411–9.
- 12 Shimazu A, Jikko A, Iwamoto M, Koike T, Yan W, Okada Y, et al. Effects of hyaluronic acid on the release of proteoglycan from the cell matrix in rabbit chondrocyte cultures in the presence and absence of cytokines. Arthritis Rheum 1993; 36: 247–53.
- 13 Stove J, Gerlach C, Huch K, Gunther KP, Puhl W, Scharf HP. Effects of hyaluronan on proteoglycan content of osteoarthritic chondrocytes in vitro. J Orthop Res 2002; 20: 551–5.
- 14
Bayliss MT,
Dudhia J.
Hyaluronan synthesis in human articular cartilage. In:
J Kennedy,
G Phillips,
P Williams,
V Hascall, editors.
Hyaluronan.
Cambridge:
MFK Group Ltd.;
2002. p.
297–302.
10.1533/9781845693121.297 Google Scholar
- 15 Dahl L, Dahl IM, Engstrom-Laurent A. Concentration and molecular weight of sodium hyaluronate in synovial fluid from patients with rheumatoid arthritis and other arthropathies. Ann Rheum Dis 1985; 44: 817–22.
- 16 Nishida Y, Knudson CB, Eger W, Kuettner KE, Knudson W. Osteogenic protein 1 stimulates cell-associated matrix assembly by normal human articular chondrocytes: up-regulation of hyaluronan synthase, CD44, and aggrecan. Arthritis Rheum 2000; 43: 206–14.
- 17 Rasmussen TB, Uttenthal A, de Stricker K, Belak S, Storgaard T. Development of a novel quantitative real-time RT-PCR assay for the simultaneous detection of all serotypes of foot-and-mouth disease virus. Arch Virol 2003; 148: 2005–21.
- 18 Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 2001; 29: e45.
- 19 Im HJ, Pacione C, Chubinskaya S, van Wijnen AJ, Sun Y, Loeser RF. Inhibitory effects of insulin-like growth factor-1 and osteogenic protein-1 on fibronectin fragment- and interleukin-1β-stimulated matrix metalloproteinase-13 expression in human chondrocytes. J Biol Chem 2003; 278: 25386–94.
- 20 Fernandez-Resa P, Mira E, Quesada AR. Enhanced detection of casein zymography of matrix metalloproteinases. Anal Biochem 1995; 224: 434–5.
- 21 Flannery CR, Little CB, Caterson B, Hughes CE. Effects of culture conditions and exposure to catabolic stimulators (IL-1 and retinoic acid) on the expression of matrix metalloproteinases (MMPs) and disintegrin metalloproteinases (ADAMs) by articular cartilage chondrocytes. Matrix Biol 1999; 18: 225–37.
- 22 Beehler BC, Hei YJ, Chen S, Lupisella JA, Ostrowski J, Starrett JE, et al. Inhibition of disease progression by a novel retinoid antagonist in animal models of arthritis. J Rheumatol 2003; 30: 355–63.
- 23 Ghayor C, Chadjichristos C, Herrouin JF, Ala-Kokko L, Suske G, Pujol JP, et al. Sp3 represses the Sp1-mediated transactivation of the human COL2A1 gene in primary and de-differentiated chondrocytes. J Biol Chem 2001; 276: 36881–95.
- 24 Deere M, Rhoades Hall C, Gunning KB, LeFebvre V, Ridall AL, Hecht JT. Analysis of the promoter region of human cartilage oligomeric matrix protein. Matrix Biol 2001; 19: 783–92.
- 25 Homandberg GA, Meyers R, Xie DL. Fibronectin fragments cause release of IL-1 from human cartilage in vitro. Clin Physiol 1993; 10: 1–6.
- 26 McKee CM, Penno MB, Cowman M, Burdick MD, Strieter RM, Bao C, et al. Hyaluronan (HA) fragments induce chemokine gene expression in alveolar macrophages: the role of HA size and CD44. J Clin Invest 1996; 98: 2403–13.
- 27 Hodge-Dufour J, Noble PW, Horton MR, Bao C, Wysoka M, Burdick MD, et al. Induction of IL-12 and chemokines by hyaluronan requires adhesion-dependent priming of resident but not elicited macrophages. J Immunol 1997; 159: 2492–500.
- 28 Chambon P. A decade of molecular biology of retinoic acid receptors. FASEB J 1996; 10: 940–54.
- 29 Bi W, Deng JM, Zhang Z, Behringer RR, de Crombrugghe B. Sox9 is required for cartilage formation. Nat Genet 1999; 22: 85–9.
- 30 Weston AD, Chandraratna RA, Torchia J, Underhill TM. Requirement for RAR-mediated gene repression in skeletal progenitor differentiation. J Cell Biol 2002; 158: 39–51.
- 31 Nishihara A, Fujii M, Sampath TK, Miyazono K, Reddi AH. Bone morphogenetic protein signaling in articular chondrocyte differentiation. Biochem Biophys Res Commun 2003; 301: 617–22.
- 32 Sylvester J, Liacini A, Li WQ, Dehnade F, Zafarullah M. Tripterygium wilfordii Hook F extract suppresses proinflammatory cytokine-induced expression of matrix metalloproteinase genes in articular chondrocytes by inhibiting activating protein-1 and nuclear factor-κB activities. Mol Pharmacol 2001; 59: 1196–205.
- 33 Liacini A, Sylvester J, Li WQ, Zafarullah M. Inhibition of interleukin-1-stimulated MAP kinases, activating protein-1 (AP-1) and nuclear factor κ B (NF-κB) transcription factors down-regulates matrix metalloproteinase gene expression in articular chondrocytes. Matrix Biol 2002; 21: 251–62.
- 34 Julovi SM, Yasuda T, Shimizu M, Hiramitsu T, Nakamura T. Inhibition of interleukin-1β–stimulated production of matrix metalloproteinases by hyaluronan via CD44 in human articular cartilage. Arthritis Rheum 2004; 50: 516–25.
- 35 Spessotto P, Rossi FM, Degan M, di Francia R, Perris R, Colombatti A, et al. Hyaluronan-CD44 interaction hampers migration of osteoclast-like cells by down-regulating MMP-9. J Cell Biol 2002; 158: 1133–44.
- 36 Kohda D, Morton CJ, Parkar AA, Hatanaka H, Inagaki FM, Campbell ID, et al. Solution structure of the link module: a hyaluronan-binding domain involved in extracellular matrix stability and cell migration. Cell 1996; 86: 767–75.
- 37
Varedi M,
Ghahary A,
Scott PG,
Tredget EE.
Cytoskeleton regulates expression of genes for transforming growth factor-β1 and extracellular matrix proteins in dermal fibroblasts.
J Cell Physiol
1997;
172:
192–9.
10.1002/(SICI)1097-4652(199708)172:2<192::AID-JCP6>3.0.CO;2-J CAS PubMed Web of Science® Google Scholar
- 38 Ogata Y, Pratta MA, Nagase H, Arner EC. Matrix metalloproteinase 9 (92-kDa gelatinase/type IV collagenase) is induced in rabbit articular chondrocytes by cotreatment with interleukin 1β and a protein kinase C activator. Exp Cell Res 1992; 201: 245–9.
- 39 Tanaka S, Hamanishi C, Kikuchi H, Fukuda K. Factors related to degradation of articular cartilage in osteoarthritis: a review. Semin Arthritis Rheum 1998; 27: 392–9.
- 40 Fitzgerald KA, Bowie AG, Skeffington BS, O'Neill LA. Ras, protein kinase C ζ, and I κ B kinases 1 and 2 are downstream effectors of CD44 during the activation of NF-κB by hyaluronic acid fragments in T-24 carcinoma cells. J Immunol 2000; 164: 2053–63.
- 41 Saito S, Yamaji N, Yasunaga K, Saito T, Matsumoto S, Katoh M, et al. The fibronectin extra domain A activates matrix metalloproteinase gene expression by an interleukin-1-dependent mechanism. J Biol Chem 1999; 274: 30756–63.
- 42
Yasuda T,
Poole AR.
A fibronectin fragment induces type II collagen degradation by collagenase through an interleukin-1–mediated pathway.
Arthritis Rheum
2002;
46:
138–48.
10.1002/1529-0131(200201)46:1<138::AID-ART10051>3.0.CO;2-K CAS PubMed Web of Science® Google Scholar
- 43 Mitchell PG, Magna HA, Reeves LM, Lopresti-Morrow LL, Yocum SA, Rosner PJ, et al. Cloning, expression, and type II collagenolytic activity of matrix metalloproteinase-13 from human osteoarthritic cartilage. J Clin Invest 1996; 97: 761–8.
- 44 Fosang AJ, Last K, Knauper V, Murphy G, Neame PJ. Degradation of cartilage aggrecan by collagenase-3 (MMP-13). FEBS Lett 1996; 380: 17–20.
- 45 Jimenez MJ, Balbin M, Alvarez J, Komori T, Bianco P, Holmbeck K, et al. A regulatory cascade involving retinoic acid, Cbfa1, and matrix metalloproteinases is coupled to the development of a process of perichondrial invasion and osteogenic differentiation during bone formation. J Cell Biol 2001; 155: 1333–44.
- 46 Mengshol JA, Vincenti MP, Coon CI, Barchowsky A, Brinckerhoff CE. Interleukin-1 induction of collagenase 3 (matrix metalloproteinase 13) gene expression in chondrocytes requires p38, c-Jun N-terminal kinase, and nuclear factor κB: differential regulation of collagenase 1 and collagenase 3. Arthritis Rheum 2000; 43: 801–11.
- 47 Nishida N, Knudson CB, Knudson W. Extracellular matrix recovery by human articular chondrocytes after treatment with hyaluronan hexasaccharides or Streptomyces hyaluronidase. Mod Rheumatol 2003; 13: 62–8.
