Physiologie und Pathophysiologie des Gelenkknorpels

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
• 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
• 3 Mohr W. Gelenkkrankheiten. Stuttgart, New York; Georg Thieme Verlag 1984
• 4 Pullig O, Pfander D, Swoboda B. [Molecular principles of induction and progression of arthrosis].  Orthopäde. 2001;  30 825-833
• 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
• 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
• 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
• 8 Hardingham T E. Proteoglycans - their structure interactions and molecular organization in cartilage.  Biochem Soc Trans. 1981;  30 489-497
• 9 Bruckner P, van der Rest M. Structure and function of cartilage collagens.  Microsc Res Tech. 1994;  30 378-384
• 10 Heinegard D, Oldberg A. Structure and biology of cartilage and bone matrix noncollagenous macromolecules.  Faseb J. 1989;  30 2042-2051
• 11 Mayne R. Cartilage collagens. What is their function, and are they involved in cartilage disease?.  Arthritis Rheum. 1989;  30 241-246
• 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
• 13 Maroudas A, Evans H. A study of ionic equilibria in cartilage.  Conn Tiss Res. 1974;  30 69-79
• 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
• 15 Neame P J, Tapp H, Azizan A. Noncollagenous, nonproteoglycan macromolecules of cartilage.  Cell Mol Life Sci. 1999;  30 1327-1340
• 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
• 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
• 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
• 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
• 20 Beguin J, Locker B. Chondropathie rotulienne. In 2ème Journèe d’arthroscopie du genou.  1983;  30 89-90
• 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
• 22 Otte P. Systematik des Arthroseprozesses und Zuordnung des pathophysiologischen Phänomens. Frankfurt; PMI Press 1987
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 31 Gay S, Rhodes R. Immunhistochemical demonstration of distinct collagens in normal and osteoarthritic joints.  Sem Arthritis Rheum. 1981;  30 43-44
• 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
• 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
• 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
• 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
• 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
• 37 Lippiello L, Hall D, Mankin H. Collagen synthesis in normal and osteoarthritic human cartilage.  J Clin Invest. 1977;  30 593-600
• 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
• 39 Pullig O, Weseloh G, Swoboda B. Expression of type VI collagen in normal and osteoarthritic human cartilage.  Osteoarthritis Cartilage. 1999;  30 191-202
• 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
• 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
• 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
• 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
• 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
• 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
• 46 Pfander D, Kortje D, Weseloh G. et al . [Cell proliferation in human arthrotic joint cartilage].  Z Orthop Ihre Grenzgeb. 2001;  30 375-381
• 47 Dustmann H, Puhl W, Krempien B. Das Phänomen der Cluster im Arthroseknorpel. Tierexperimentelle Untersuchungen.  Arch Orthop Unfallchir. 1974;  30 321-333
• 48 Telhag H. Mitosis of chondrocytes in experimental „osteoarthritis” in rabbits.  Clin Orthop Rel Res. 1972;  30 224-229
• 49 Heraud F, Heraud M, Harmand M. Apoptosis in normal and osteoarthritic human articular cartilage.  Ann Rheum Dis. 2000;  30 959-965
• 50 Blanco F, Guitian R, Vazquez-Martul E. et al . Osteoarthritis chondrocytes die by apoptosis.  Arthritis Rheum. 1998;  30 284-289
• 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
• 52 Aigner T, Kim H A. Apoptosis and cellular vitality: issues in osteoarthritic cartilage degeneration.  Arthritis Rheum. 2002;  30 1986-1996
• 53 Aigner T. Apoptosis, necrosis, or whatever: how to find out what really happens?.  J Pathol. 2002;  30 1-4
• 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
• 55 Pauwels F. Atlas zur Biomechanik der gesunden und kranken Hüfte. Berlin, Heidelberg, New York; Springer 1973
• 56 Hackenbroch M. Präarthrose und präarthrotische Deformität.  Z Orthop. 1978;  30 418-422
• 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
• 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
• 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
• 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
• 61 Sah R, Kim Y, Doong J. et al . Biosynthetic response of cartilage explants to dynamic compression.  J Orthop Res. 1989;  30 619-626
• 62 Steinmeyer J, Ackermann B, Raiss R X. Intermittent cyclic loading of cartilage explants modulates fibronectin metabolism.  Osteoarthritis Cartilage. 1997;  30 331-341
• 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
• 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
• 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
• 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
• 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
• 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
• 69 Lane N E. Exercise: a cause of osteoarthritis.  J Rheumatol. 1995;  30 3-6
• 70 Panush R S, Lane N E. Exercise and the musculoskeletal system.  Baillieres Clin Rheumatol. 1994;  30 79-102
• 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
• 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
• 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
• 74 Felson D T. Weight and osteoarthritis.  J Rheumatol. 1995;  30 7-9
• 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
• 76 Pujol J P, Loyau G. Interleukin-1 and osteoarthritis.  Life Sci. 1987;  30 1187-1198
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 86 Doyle D V. Tissue calcification and inflammation in osteoarthritis.  J Pathol. 1982;  30 199-216
• 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
• 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
• 89 Urban J P. The chondrocyte: A cell under pressure.  Br J Rheumatol. 1994;  30 901-908
• 90 Richman A I, Su E Y, Ho G. Reciprocal relationship of synovial fluid volume and oxygen tension.  Arthritis Rheum. 1981;  30 701-705
• 91 Schneider U, Miltner O, Graf J. et al . Intraarticular oxygen partial pressure measurements under working conditions.  Orthop Trans. 1994;  30 58
• 92 Schneider U, Miltner O, Thomsen M. et al . Intraartikuläre Sauerstoffpartialdruckmesung unter funtionellen Bedingungen.  Z Orthop. 1996;  30 422-425
• 93 Lund-Olesen K. Oxygen tension in synovial fluids.  Arthritis Rheum. 1970;  30 769-776
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 104 Pfander D, Cramer T, Swoboda B. Hypoxia and HIF-1alpha in osteoarthritis.  Int Orthop. 2005;  30 6-9
• 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
• 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