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Aktuelle Rheumatologie 2005; 30(6): 344-353
DOI: 10.1055/s-2005-858868
Originalarbeit

© Georg Thieme Verlag KG Stuttgart · New York

Physiologie und Pathophysiologie des Gelenkknorpels

Physiology and Pathophysiology of Joint CartilageD. Pfander1
  • 1Abteilung für Orthopädische Rheumatologie, Orthopädische Klinik mit Poliklinik der Friedrich-Alexander Universität Erlangen-Nürnberg
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Publication History

Publication Date:
09 December 2005 (online)

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Zusammenfassung

Synoviale Gelenke sind komplexe Funktionseinheiten, welche uns die Bewegung und Belastung der Extremitäten im dreidimensionalen Raum ermöglichen. Die häufigste Erkrankung der synovialen Gelenke ist die Osteoarthrose, die vor allem durch den fortschreitenden Knorpelschaden gekennzeichnet ist. In dieser Arbeit geben wir einen Überblick über die Physiologie des hyalinen Gelenkknorpels und die verschiedenen pathophysiologischen Modelle seiner Schädigung während des Arthroseprozesses.

Abstract

Synovial joints are highly complex functional units, which allow motion and mechanical loading of upper and lower extremities in the three-dimensional space. Osteoarthritis is the most common joint disease, most prominently characterized by a progressive damage of hyaline cartilage. In this paper, we provide an overview of the physiology of hyaline cartilage and different pathophysiological concepts of cartilage destruction, during the course of osteoarthritis.

Schlüsselwörter

Arthrose - Knorpel - Pathophysiologie

Key words

Osteoarthritis - cartilage - pathophysiology

Literatur

  • 1 Yelin E, Callahan L F. The economic cost and social and psychological impact of musculoskeletal conditions.  Arthritis Rheum. 1995;  30 1351-1362
    PubMedGoogle Scholar
  • 2 Felson D T, Zhang Y, Hannan M T. et al . The incidence and natural history of knee osteoarthritis in the eldery: The Framingham osteoarthritis study.  Arthritis Rheum. 1995;  30 1500-1505
    PubMedGoogle Scholar
  • 3 Mohr W. Gelenkkrankheiten. Stuttgart, New York; Georg Thieme Verlag 1984
    Google Scholar
  • 4 Pullig O, Pfander D, Swoboda B. [Molecular principles of induction and progression of arthrosis].  Orthopäde. 2001;  30 825-833
    CrossrefPubMedGoogle Scholar
  • 5 Pelletier J P, Martel-Pelletier J. [Role of synovial inflammation, cytokines and IGF-1 in the physiopathology of osteoarthritis].  Rev Rhum Ed Fr. 1994;  30 103S-108S
    PubMedGoogle Scholar
  • 6 Moos V, Fickert S, Müller B. et al . Immunohistological analysis of cytokine expression in human osteoarthritic and healthy cartilage.  J Rheumatol. 1999;  30 870-879
    PubMedGoogle Scholar
  • 7 Pelletier J P, Caron J P, Evans C. et al . In vivo suppression of early experimental osteoarthritis by interleukin-1 receptor antagonist using gene therapy.  Arthritis Rheum. 1997;  30 1012-1019
    PubMedGoogle Scholar
  • 8 Hardingham T E. Proteoglycans - their structure interactions and molecular organization in cartilage.  Biochem Soc Trans. 1981;  30 489-497
    PubMedGoogle Scholar
  • 9 Bruckner P, van der Rest M. Structure and function of cartilage collagens.  Microsc Res Tech. 1994;  30 378-384
    PubMedGoogle Scholar
  • 10 Heinegard D, Oldberg A. Structure and biology of cartilage and bone matrix noncollagenous macromolecules.  Faseb J. 1989;  30 2042-2051
    PubMedGoogle Scholar
  • 11 Mayne R. Cartilage collagens. What is their function, and are they involved in cartilage disease?.  Arthritis Rheum. 1989;  30 241-246
    PubMedGoogle Scholar
  • 12 Aigner T, Stöve J. Collagens-major component of the physiological matrix, major target of cartilage degeneration, major tool in cartilage repair.  Advanced Drug Delivery Reviews. 2003;  30 1569-1593
    PubMedGoogle Scholar
  • 13 Maroudas A, Evans H. A study of ionic equilibria in cartilage.  Conn Tiss Res. 1974;  30 69-79
    PubMedGoogle Scholar
  • 14 Maroudas A, Bannon C. Measurement of swelling pressure in cartilage and comparison with the osmotic pressure of constituent proteoglycans.  Biorheology. 1981;  30 619-632
    PubMedGoogle Scholar
  • 15 Neame P J, Tapp H, Azizan A. Noncollagenous, nonproteoglycan macromolecules of cartilage.  Cell Mol Life Sci. 1999;  30 1327-1340
    PubMedGoogle Scholar
  • 16 Mollenhauer J, Mok M T, King K B. et al . Expression of anchorin CII (cartilage annexin V) in human young, normal adult, and osteoarthritic cartilage.  J Histochem Cytochem. 1999;  30 209-222
    PubMedGoogle Scholar
  • 17 Pfander D, Swoboda B, Kirsch T. Expression of early and late differentiation markers (proliferating cell nuclear antigen, syndecan-3, annexin VI, and alkaline phosphatase) by human osteoarthritic chondrocytes.  Am J Pathol. 2001;  30 1777-1783
    PubMedGoogle Scholar
  • 18 Pfander D, Rahmanzadeh R, Scheller E E. Presence and distribution of collagen II, collagen I, fibronectin, and tenascin in rabbit normal and osteoarthritic cartilage.  J Rheumatol. 1999;  30 386-394
    PubMedGoogle Scholar
  • 19 Pullig O, Weseloh G, Klatt A R. et al . Matrilin-3 in human articular cartilage: increased expression in osteoarthritis.  Osteoarthritis Cartilage. 2002;  30 253-263
    PubMedGoogle Scholar
  • 20 Beguin J, Locker B. Chondropathie rotulienne. In 2ème Journèe d’arthroscopie du genou.  1983;  30 89-90
    PubMedGoogle Scholar
  • 21 Dougados M, Ayral X, Listrat V. et al . The SFA system for assessing articular cartilage lesions at arthroscopy of the knee.  Arthroscopy. 1994;  30 69-77
    PubMedGoogle Scholar
  • 22 Otte P. Systematik des Arthroseprozesses und Zuordnung des pathophysiologischen Phänomens. Frankfurt; PMI Press 1987
    Google Scholar
  • 23 Aigner T, Zien A, Gehrsitz A. et al . Anabolic and catabolic gene expression pattern analysis in normal versus osteoarthritic cartilage using DNA-Array technology.  Arthritis Rheum. 2001;  30 2777-2789
    PubMedGoogle Scholar
  • 24 van den Berg W B, van der Kraan P M, van Beuningen H M. Role of growth factors and cartilage repair. Reginster JY, Pelletier JP, Martel-Pelletier J, Henrotin Y Osteoarthritis. Clinical and experimental aspects Berlin, Heidelberg, New York; Springer 1999: 188-209
    Google Scholar
  • 25 Kobayashi M, Squires G R, Mousa A. et al . Role of interleukin-1 and tumor necrosis factor alpha in matrix degradation of human osteoarthritic cartilage.  Arthritis Rheum. 2005;  30 128-135
    PubMedGoogle Scholar
  • 26 Cawston T, Billington C, Cleaver C. et al . The regulation of MMP’s and TIMP’s in cartilage turnover.  Ann N Y Acad Sci. 1999;  30 120-129
    PubMedGoogle Scholar
  • 27 Glasson S S, Askew R, Sheppard B. et al . Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis.  Nature. 2005;  30 644-648
    PubMedGoogle Scholar
  • 28 Aigner T, Bertling W, Stöss H. et al . Independent expression of fibril-forming collagens I, II and III in chondrocytes of human osteoarthritic cartilage.  J Clin Invest. 1993;  30 829-837
    PubMedGoogle Scholar
  • 29 Von der Mark K, Kirsch T, Nerlich A. et al . Type X collagen synthesis in human osteoarthritic cartilage.  Arthritis Rheum. 1992;  30 806-811
    PubMedGoogle Scholar
  • 30 Aigner T, Gluckert K, von der Mark K. Activation of fibrillar collagen synthesis and phenotypic modulation of chondrocytes in early human osteoarthritic cartilage lesions.  Osteoarthritis Cartilage. 1997;  30 183-189
    PubMedGoogle Scholar
  • 31 Gay S, Rhodes R. Immunhistochemical demonstration of distinct collagens in normal and osteoarthritic joints.  Sem Arthritis Rheum. 1981;  30 43-44
    PubMedGoogle Scholar
  • 32 Pullig O, Weseloh G, Gauer S. et al . Osteopontin is expressed by adult human osteoarthritic chondrocytes: protein and mRNA analysis of normal and osteoarthritic cartilage.  Matrix Biol. 2000;  30 245-255
    PubMedGoogle Scholar
  • 33 Pullig O, Weseloh G, Ronneberger D. et al . Chondrocyte differentiation in human osteoarthritis: expression of osteocalcin in normal and osteoarthritic cartilage and bone.  Calcif Tissue Int. 2000;  30 230-240
    PubMedGoogle Scholar
  • 34 Kirsch T, Swoboda B, Nah H. Activation of annexin II and V expression, terminal differentiation, mineralization and apoptosis in human osteoarthritic cartilage.  Osteoarthritis Cartilage. 2000;  30 294-302
    PubMedGoogle Scholar
  • 35 Hashimoto S, Ochs R, Rosen F. et al . Chondrocyte-derived apoptotic bodies and calcification of articular cartilage.  Proc Natl Acad Sci. 1998;  30 3094-3099
    PubMedGoogle Scholar
  • 36 Hatori M, Klatte K J, Teixeira C C. et al . End labeling studies of fragmented DNA in the avian growth plate: evidence of apoptosis in terminally differentiated chondrocytes.  J Bone Miner Res. 1995;  30 1960-1968
    PubMedGoogle Scholar
  • 37 Lippiello L, Hall D, Mankin H. Collagen synthesis in normal and osteoarthritic human cartilage.  J Clin Invest. 1977;  30 593-600
    PubMedGoogle Scholar
  • 38 Nelson F, Dahlberg L, Laverty S. et al . Evidence for altered synthesis of type II collagen in patients with osteoarthritis.  J Clin Invest. 1998;  30 2115-2125
    PubMedGoogle Scholar
  • 39 Pullig O, Weseloh G, Swoboda B. Expression of type VI collagen in normal and osteoarthritic human cartilage.  Osteoarthritis Cartilage. 1999;  30 191-202
    PubMedGoogle Scholar
  • 40 Swoboda B, Pullig O, Kirsch T. et al . Increased content of type-VI collagen epitopes in human osteoarthritic cartilage: quantitation by inhibition ELISA.  J Orthop Res. 1998;  30 96-99
    PubMedGoogle Scholar
  • 41 Pfander D, Heinz N, Rothe P. et al . Tenascin and aggrecan expression by articular chondrocytes is influenced by interleukin 1beta: a possible explanation for the changes in matrix synthesis during osteoarthritis.  Ann Rheum Dis. 2004;  30 240-244
    PubMedGoogle Scholar
  • 42 Yasuda T, Poole A R. A fibronectin fragment induces type II collagen degradation by collagenase through an interleukin-1-mediated pathway.  Arthritis Rheum. 2002;  30 138-148
    PubMedGoogle Scholar
  • 43 Miller R R, Mc Devitt C A. Thrombospondin is present in articular cartilage and is synthesized by articular chondrocytes.  Biochem Biophys Res Commun. 1988;  30 708-714
    PubMedGoogle Scholar
  • 44 Pfander D, Cramer T, Deuerling D. et al . Expression of thrombospondin-1 and its receptor CD36 in human osteoarthritic cartilage.  Ann Rheum Dis. 2000;  30 448-454
    PubMedGoogle Scholar
  • 45 Gebauer M, Saas J, Haag J. et al . Repression of anti-proliferative factor Tob1 in osteoarthritic cartilage.  Arthritis Res Ther. 2005;  30 R274-284
    PubMedGoogle Scholar
  • 46 Pfander D, Kortje D, Weseloh G. et al . [Cell proliferation in human arthrotic joint cartilage].  Z Orthop Ihre Grenzgeb. 2001;  30 375-381
    Article in Thieme ConnectPubMedGoogle Scholar
  • 47 Dustmann H, Puhl W, Krempien B. Das Phänomen der Cluster im Arthroseknorpel. Tierexperimentelle Untersuchungen.  Arch Orthop Unfallchir. 1974;  30 321-333
    PubMedGoogle Scholar
  • 48 Telhag H. Mitosis of chondrocytes in experimental „osteoarthritis” in rabbits.  Clin Orthop Rel Res. 1972;  30 224-229
    PubMedGoogle Scholar
  • 49 Heraud F, Heraud M, Harmand M. Apoptosis in normal and osteoarthritic human articular cartilage.  Ann Rheum Dis. 2000;  30 959-965
    PubMedGoogle Scholar
  • 50 Blanco F, Guitian R, Vazquez-Martul E. et al . Osteoarthritis chondrocytes die by apoptosis.  Arthritis Rheum. 1998;  30 284-289
    PubMedGoogle Scholar
  • 51 Hashimoto S, Setareh M, Ochs R. et al . Fas/Fas ligand expression and induction of apoptosis in chondrocytes.  Arthritis Rheum. 1997;  30 1749-1755
    PubMedGoogle Scholar
  • 52 Aigner T, Kim H A. Apoptosis and cellular vitality: issues in osteoarthritic cartilage degeneration.  Arthritis Rheum. 2002;  30 1986-1996
    PubMedGoogle Scholar
  • 53 Aigner T. Apoptosis, necrosis, or whatever: how to find out what really happens?.  J Pathol. 2002;  30 1-4
    PubMedGoogle Scholar
  • 54 Hodge W A, Fijan R S, Carlson K L. et al . Contact pressures in the human hip joint measured in vivo.  Proc Natl Acad Sci U S A. 1986;  30 2879-2883
    PubMedGoogle Scholar
  • 55 Pauwels F. Atlas zur Biomechanik der gesunden und kranken Hüfte. Berlin, Heidelberg, New York; Springer 1973
    Google Scholar
  • 56 Hackenbroch M. Präarthrose und präarthrotische Deformität.  Z Orthop. 1978;  30 418-422
    PubMedGoogle Scholar
  • 57 Burton-Wurster N, Vernier-Singer M, Farquhar T. et al . Effect of compressive loading and unloading on the synthesis of total protein, proteoglycan, and fibronectin by canine cartilage explants.  J Orthop Res. 1993;  30 717-729
    PubMedGoogle Scholar
  • 58 Palmoski M J, Brandt K D. Effects of static and cyclic compressive loading on articular cartilage plugs in vitro.  Arthritis Rheum. 1984;  30 675-681
    PubMedGoogle Scholar
  • 59 De Witt M T, Handley C J, Oakes B W. et al . In vitro response of chondrocytes to mechanical loading. The effect of short term mechanical tension.  Connect Tissue Res. 1984;  30 97-109
    PubMedGoogle Scholar
  • 60 Buschmann M, Gluzband Y, Grodzinsky A. et al . Mechanical compression modulates matrix biosynthesis in chondrocyte/agarose culture.  J Cell Sci. 1995;  30 1497-1508
    PubMedGoogle Scholar
  • 61 Sah R, Kim Y, Doong J. et al . Biosynthetic response of cartilage explants to dynamic compression.  J Orthop Res. 1989;  30 619-626
    PubMedGoogle Scholar
  • 62 Steinmeyer J, Ackermann B, Raiss R X. Intermittent cyclic loading of cartilage explants modulates fibronectin metabolism.  Osteoarthritis Cartilage. 1997;  30 331-341
    PubMedGoogle Scholar
  • 63 Sauerland K, Raiss R X, Steinmeyer J. Proteoglycan metabolism and viability of articular cartilage explants as modulated by the frequency of intermittent loading.  Osteoarthritis Cartilage. 2003;  30 343-350
    PubMedGoogle Scholar
  • 64 Fehrenbacher A, Steck E, Rickert M. et al . Rapid regulation of collagen but not metalloproteinase 1, 3, 13, 14 and tissue inhibitor of metalloproteinase 1, 2, 3 expression in response to mechanical loading of cartilage explants in vitro.  Arch Biochem Biophys. 2003;  30 39-47
    PubMedGoogle Scholar
  • 65 Kiviranta I, Tammi M, Jurvelin J. et al . Moderate running exercise augments glycosaminoglycans and thickness of articular cartilage in the knee joint of young beagle dogs.  J Orthop Res. 1988;  30 188-195
    PubMedGoogle Scholar
  • 66 Jortikka M O, Inkinen R I, Tammi M I. et al . Immobilisation causes longlasting matrix changes both in the immobilised and contralateral joint cartilage.  Ann Rheum Dis. 1997;  30 255-261
    PubMedGoogle Scholar
  • 67 Kiviranta I, Jurvelin J, Tammi M. et al . Weight bearing controls glycosaminoglycan concentration and articular cartilage thickness in the knee joints of young beagle dogs.  Arthritis Rheum. 1987;  30 801-809
    PubMedGoogle Scholar
  • 68 Arokoski J, Kiviranta I, Jurvelin J. et al . Long-distance running causes site dependent decrease of cartilage glycosaminoglycan content in the knee joints of beagle dogs.  Arthritis Rheum. 1993;  30 1451-1459
    PubMedGoogle Scholar
  • 69 Lane N E. Exercise: a cause of osteoarthritis.  J Rheumatol. 1995;  30 3-6
    PubMedGoogle Scholar
  • 70 Panush R S, Lane N E. Exercise and the musculoskeletal system.  Baillieres Clin Rheumatol. 1994;  30 79-102
    PubMedGoogle Scholar
  • 71 Hannan M T, Felson D T, Anderson J J. et al . Habitual physical activity is not associated with knee osteoarthritis: the Framingham Study.  J Rheumatol. 1993;  30 704-709
    PubMedGoogle Scholar
  • 72 Felson D T, Naimark A, Anderson J. et al . The prevalence of knee osteoarthritis in the elderly. The Framingham Osteoarthritis Study.  Arthritis Rheum. 1987;  30 914-918
    CrossrefPubMedGoogle Scholar
  • 73 Felson D T, Goggins J, Niu J. et al . The effect of body weight on progression of knee osteoarthritis is dependent on alignment.  Arthritis Rheum. 2004;  30 3904-3909
    PubMedGoogle Scholar
  • 74 Felson D T. Weight and osteoarthritis.  J Rheumatol. 1995;  30 7-9
    PubMedGoogle Scholar
  • 75 Felson D T, Zhang Y, Hannan M T. et al . Risk factors for incident radiographic knee osteoarthritis in the elderly: the Framingham Study.  Arthritis Rheum. 1997;  30 728-733
    PubMedGoogle Scholar
  • 76 Pujol J P, Loyau G. Interleukin-1 and osteoarthritis.  Life Sci. 1987;  30 1187-1198
    PubMedGoogle Scholar
  • 77 Pelletier J P, Faure M P, DiBattista J A. et al . Coordinate synthesis of stromelysin, interleukin-1, and oncogene proteins in experimental osteoarthritis. An immunohistochemical study.  Am J Pathol. 1993;  30 95-105
    PubMedGoogle Scholar
  • 78 Nietfeld J J, Wilbrink B, Helle M. et al . Interleukin-1-induced interleukin-6 is required for the inhibition of proteoglycan synthesis by interleukin-1 in human articular cartilage.  Arthritis Rheum. 1990;  30 1695-1701
    PubMedGoogle Scholar
  • 79 Tetlow L C, Adlam D J, Wooley D E. Matrix metalloproteinase and proinflammatory cytokine production by chondrocytes of human osteoarthritic cartilage: associations with degenerative changes.  Arthritis Rheumatism. 2001;  30 585-594
    PubMedGoogle Scholar
  • 80 Smith M D, Triantafillou S, Parker A. Synovial membrane inflammation and cytokine production in patients with early osteoarthritis.  J Rheumatol. 1997;  30 365-371
    PubMedGoogle Scholar
  • 81 Goldring M B, Birkhead J, Sandell L J. et al . Interleukin-1 suppresses expression of cartilage-specific types II and IX collagens and increases types I and III collagens in human chondrocytes.  J Clin Invest. 1988;  30 2026-2037
    PubMedGoogle Scholar
  • 82 Pfander D, Heinz N, Rothe P. et al . Tenascin and aggrecan expression by articular chondrocytes is influenced by IL-1beta. A possible explanation for changes in matrix synthesis during OA.  Ann Rheum Dis Ann Rheum Dis. 2004;  30 240-244
    PubMedGoogle Scholar
  • 83 Nalbant S, Martinez J A, Kitumnuaypong T. et al . Synovial fluid features and their relations to osteoarthritis severity: new findings from sequential studies.  Osteoarthritis Cartilage. 2003;  30 50-54
    PubMedGoogle Scholar
  • 84 Felson D T, Anderson J J, Naimark A. et al . The prevalence of chondrocalcinosis in the elderly and its association with knee osteoarthritis: the Framingham Study.  J Rheumatol. 1989;  30 1241-1245
    PubMedGoogle Scholar
  • 85 Carroll G J, Stuart R A, Armstrong J A. et al . Hydroxyapatite crystals are a frequent finding in osteoarthritic synovial fluid, but are not related to increased concentrations of keratan sulfate or interleukin 1 beta.  J Rheumatol. 1991;  30 861-866
    PubMedGoogle Scholar
  • 86 Doyle D V. Tissue calcification and inflammation in osteoarthritis.  J Pathol. 1982;  30 199-216
    PubMedGoogle Scholar
  • 87 Reuge L, Van Linthoudt D, Gerster J C. Local deposition of calcium pyrophosphate crystals in evolution of knee osteoarthritis.  Clin Rheumatol. 2001;  30 428-431
    PubMedGoogle Scholar
  • 88 Derfus B, Kranendok S, Camacho N. et al . Human osteoarthritic cartilage matrix vesicles generate both calcium pyrophosphate dihydrate and apatite in vitro.  Calcif Tissue Int. 1998;  30 258-262
    PubMedGoogle Scholar
  • 89 Urban J P. The chondrocyte: A cell under pressure.  Br J Rheumatol. 1994;  30 901-908
    PubMedGoogle Scholar
  • 90 Richman A I, Su E Y, Ho G. Reciprocal relationship of synovial fluid volume and oxygen tension.  Arthritis Rheum. 1981;  30 701-705
    PubMedGoogle Scholar
  • 91 Schneider U, Miltner O, Graf J. et al . Intraarticular oxygen partial pressure measurements under working conditions.  Orthop Trans. 1994;  30 58
    PubMedGoogle Scholar
  • 92 Schneider U, Miltner O, Thomsen M. et al . Intraartikuläre Sauerstoffpartialdruckmesung unter funtionellen Bedingungen.  Z Orthop. 1996;  30 422-425
    PubMedGoogle Scholar
  • 93 Lund-Olesen K. Oxygen tension in synovial fluids.  Arthritis Rheum. 1970;  30 769-776
    PubMedGoogle Scholar
  • 94 Silver I A. Measurement of pH and ionic composition of pericellular sites.  Philos Trans R Soc Lond B Biol Sci. 1975;  30 261-272
    PubMedGoogle Scholar
  • 95 Ogata K, Whiteside L, Lesker P. Subchondral route for nutrition to articular cartilage in the rabbit.  J Bone Joint Surg (Am). 1978;  30 905-910
    PubMedGoogle Scholar
  • 96 Semenza G, Nejfelt M, Chi S. et al . Hypoxia-inducible nuclear factors bind to an enhancer element located 3’ to the human erythropoietin gene.  Proc Natl Acad Sci USA. 1991;  30 5680-5684
    PubMedGoogle Scholar
  • 97 Jaakkola P, Mole D R, Tian Y M. et al . Targeting of HIF-1 a to the von Hippel-Lindau ubiquitiylation complex by O2-regulated prolyl hydroxylation.  Science. 2001;  30 468-472
    PubMedGoogle Scholar
  • 98 Semenza G L. Hif-1, O(2), and the 3 phds. How animal cells signal hypoxia to the nucleus.  Cell. 2001;  30 1-3
    PubMedGoogle Scholar
  • 99 Pfander D, Kortje D, Zimmermann R. et al . Vascular endothelial growth factor in articular cartilage of healthy and osteoarthritic human knee joints.  Ann Rheum Dis. 2001;  30 1070-1073
    PubMedGoogle Scholar
  • 100 Enomoto H, Inoki I, Komiya K. et al . Vascular endothelial growth factor isoforms and their receptors are expressed in human osteoarthritic cartilage.  Am J Pathol. 2003;  30 171-181
    PubMedGoogle Scholar
  • 101 Cramer T, Schipani E, Johnson R S. et al . Expression of VEGF isoforms by epiphyseal chondrocytes during low-oxygen tension is HIF-1 alpha dependent.  Osteoarthritis Cartilage. 2004;  30 433-439
    PubMedGoogle Scholar
  • 102 Pufe T, Petersen W, Tillmann B. et al . The splice variants VEGF121 and VEGF189 of the angiogenic peptide vascular endothelial growth factor are expressed in osteoarthritic cartilage.  Arthritis Rheum. 2001;  30 1082-1088
    PubMedGoogle Scholar
  • 103 Pfander D, Cramer T, Schipani E. et al . HIF-1alpha controls extracellular matrix synthesis by epiphyseal chondrocytes.  J Cell Sci. 2003;  30 1819-1826
    PubMedGoogle Scholar
  • 104 Pfander D, Cramer T, Swoboda B. Hypoxia and HIF-1alpha in osteoarthritis.  Int Orthop. 2005;  30 6-9
    PubMedGoogle Scholar
  • 105 Jung Y J, Isaacs J S, Lee S. et al . IL-1beta-mediated up-regulation of HIF-1alpha via an NFkappaB/COX-2 pathway identifies HIF-1 as a critical link between inflammation and oncogenesis.  FASEB J. 2003;  2115-2117
    PubMedGoogle Scholar
  • 106 Chang H, Shyu K G, Wang B W. et al . Regulation of hypoxia-inducible factor-1alpha by cyclical mechanical stretch in rat vascular smooth muscle cells.  Clin Sci (Lond). 2003;  30 447-456
    PubMedGoogle Scholar

Priv.-Doz. Dr. med. David Pfander

Abteilung für Orthopädische Rheumatologie, Orthopädische Klinik mit Poliklinik der Friedrich-Alexander-Universität Erlangen-Nürnberg

Rathsbergerstraße 57

91054 Erlangen

Phone: ++ 49/91 31/82 39 09

Email: DPfander@t-online.de

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