Update on the biology of the chondrocyte and new approaches to treating cartilage diseases

Harris, 2001, The bone and joint decade: a catalyst for progress, Arthritis and Rheumatism, 44, 1969, 10.1002/1529-0131(200109)44:9<1969::AID-ART342>3.0.CO;2-A

Felson, 2004, Risk factors for osteoarthritis: understanding joint vulnerability, Clinical Orthopaedics and Related Research, 427, S16, 10.1097/01.blo.0000144971.12731.a2

Peach, 2005, Recent advances in the genetic investigation of osteoarthritis, Trends in Molecular Medicine, 11, 186, 10.1016/j.molmed.2005.02.005

Spencer, 2005, Genetic background increases the risk of hip osteoarthritis, Clinical Orthopaedics and Related Research, 134, 10.1097/01.blo.0000149242.85548.00

Valdes, 2006, Reproducible genetic associations between candidate genes and clinical knee osteoarthritis in men and women, Arthritis and Rheumatism, 54, 533, 10.1002/art.21621

Hunter, 2005, Structural factors associated with malalignment in knee osteoarthritis: the Boston osteoarthritis knee study, The Journal of Rheumatology, 32, 2192

Lee, 2005, Mechanical injury of cartilage explants causes specific time-dependent changes in chondrocyte gene expression, Arthritis and Rheumatism, 52, 2386, 10.1002/art.21215

Loeser, 2004, Aging cartilage and osteoarthritis – what's the link?, Science of Aging Knowledge Environment, 2004, pe31, 10.1126/sageke.2004.29.pe31

Carrington, 2005, Aging bone and cartilage: cross-cutting issues, Biochemical and Biophysical Research Communications, 328, 700, 10.1016/j.bbrc.2004.12.041

Wieland, 2005, Osteoarthritis – an untreatable disease?, Nature Reviews. Drug Discovery, 4, 331, 10.1038/nrd1693

Solomon, 2005, Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention, The New England Journal of Medicine, 352, 1071, 10.1056/NEJMoa050405

Brandt, 2005, Lessons learned from nine clinical trials of disease-modifying osteoarthritis drugs, Arthritis and Rheumatism, 52, 3349, 10.1002/art.21409

Wilkins, 2000, Surviving in a matrix: membrane transport in articular chondrocytes, The Journal of Membrane Biology, 177, 95, 10.1007/s002320001103

Mobasheri, 2005, Hypoxia inducible factor-1 and facilitative glucose transporters GLUT1 and GLUT3: putative molecular components of the oxygen and glucose sensing apparatus in articular chondrocytes, Histology and Histopathology, 20, 1327

Poole, 2005, Cartilage in health and disease, 223

Goldring, 2004, Chapter 1: Biology of the normal joint, 1

Poole, 2001, Composition and structure of articular cartilage: a template for tissue repair, Clinical Orthopaedics, 391, S26, 10.1097/00003086-200110001-00004

Struglics, 2006, Human osteoarthritis synovial fluid and joint cartilage contain both aggrecanase- and matrix metalloproteinase-generated aggrecan fragments, Osteoarthritis and Cartilage, 14, 101, 10.1016/j.joca.2005.07.018

Tetlow, 2001, Matrix metalloproteinase and proinflammatory cytokine production by chondrocytes of human osteoarthritic cartilage, Arthritis and Rheumatism, 44, 585, 10.1002/1529-0131(200103)44:3<585::AID-ANR107>3.0.CO;2-C

Wu, 2002, Sites of collagenase cleavage and denaturation of type II collagen in aging and osteoarthritic articular cartilage and their relationship to the distribution of matrix metalloproteinase 1 and matrix metalloproteinase 13, Arthritis and Rheumatism, 46, 2087, 10.1002/art.10428

Guilak, 2004, The role of biomechanics and inflammation in cartilage injury and repair, Clinical Orthopaedics and Related Research, 423, 17, 10.1097/01.blo.0000131233.83640.91

Homandberg, 2001, Cartilage damage by matrix degradation products: fibronectin fragments, Clinical Orthopaedics and Related Research, 391, S100, 10.1097/00003086-200110001-00010

Pritzker, 2006, Osteoarthritis cartilage histopathology: grading and staging, Osteoarthritis and Cartilage, 14, 13, 10.1016/j.joca.2005.07.014

Hermansson, 2004, Proteomic analysis of articular cartilage shows increased type II collagen synthesis in osteoarthritis and expression of inhibin betaA (activin A), a regulatory molecule for chondrocytes, The Journal of Biological Chemistry, 279, 43514, 10.1074/jbc.M407041200

Aigner, 2004, Functional genomics of osteoarthritis: on the way to evaluate disease hypotheses, Clinical Orthopaedics and Related Research, 427, S138, 10.1097/01.blo.0000143838.53434.b8

Fukui, 2003, Stimulation of BMP-2 expression by pro-inflammatory cytokines IL-1 and TNF-α in normal and osteoarthritic chondrocytes, The Journal of Bone and Joint Surgery. American Volume, 85-A, 59, 10.2106/00004623-200300003-00011

Tchetina, 2005, Increased type II collagen degradation and very early focal cartilage degeneration is associated with upregulation of chondrocyte differentiation related genes in early human articular cartilage lesions, The Journal of Rheumatology, 32, 876

Aigner, 2003, SOX9 expression does not correlate with type II collagen expression in adult articular chondrocytes, Matrix Biology, 22, 363, 10.1016/S0945-053X(03)00049-0

Aigner, 2004, Aging theories of primary osteoarthritis: from epidemiology to molecular biology, Rejuvenation Research, 7, 134, 10.1089/1549168041552964

Goldring, 2004, The role of cytokines in cartilage matrix degeneration in osteoarthritis, Clinical Orthopaedics, 427, S27, 10.1097/01.blo.0000144854.66565.8f

Goldring, 2004, The regulation of chondrocyte function by proinflammatory mediators: prostaglandins and nitric oxide, Clinical Orthopaedics, 427, S37, 10.1097/01.blo.0000144484.69656.e4

Benito, 2005, Synovial tissue inflammation in early and late osteoarthritis, Annals of the Rheumatic Diseases, 64, 1263, 10.1136/ard.2004.025270

Malemud, 2004, Cytokines as therapeutic targets for osteoarthritis, BioDrugs, 18, 23, 10.2165/00063030-200418010-00003

Evans, 2005, Novel biological approaches to the intra-articular treatment of osteoarthritis, BioDrugs, 19, 355, 10.2165/00063030-200519060-00003

Borzi, 2004, Chemokines in cartilage degradation, Clinical Orthopaedics and Related Research, 427, S53, 10.1097/01.blo.0000143805.64755.4f

Lubberts, 2005, The role of T cell interleukin-17 in conducting destructive arthritis: lessons from animal models, Arthritis Research and Therapy, 7, 29, 10.1186/ar1478

Barksby, 2006, Interleukin-1 in combination with oncostatin M up-regulates multiple genes in chondrocytes: implications for cartilage destruction and repair, Arthritis and Rheumatism, 54, 540, 10.1002/art.21574

Denko, 2005, Role of the growth hormone/insulin-like growth factor-1 paracrine axis in rheumatic diseases, Seminars in Arthritis and Rheumatism, 35, 24, 10.1016/j.semarthrit.2005.03.001

Bobacz, 2003, Expression of bone morphogenetic protein 6 in healthy and osteoarthritic human articular chondrocytes and stimulation of matrix synthesis in vitro, Arthritis and Rheumatism, 48, 2501, 10.1002/art.11248

Chubinskaya, 2002, Age-related changes in cartilage endogenous osteogenic protein-1 (OP-1), Biochimica et Biophysica Acta, 1588, 126, 10.1016/S0925-4439(02)00158-8

Blaney Davidson, 2005, Reduced transforming growth factor-beta signaling in cartilage of old mice: role in impaired repair capacity, Arthritis Research and Therapy, 7, R1338, 10.1186/ar1833

Loeser, 2003, The combination of insulin-like growth factor 1 and osteogenic protein 1 promotes increased survival of and matrix synthesis by normal and osteoarthritic human articular chondrocytes, Arthritis and Rheumatism, 48, 2188, 10.1002/art.11209

Loeser, 2005, Basic fibroblast growth factor inhibits the anabolic activity of insulin-like growth factor 1 and osteogenic protein 1 in adult human articular chondrocytes, Arthritis and Rheumatism, 52, 3910, 10.1002/art.21472

Iwanaga, 2005, Enhanced expression of insulin-like growth factor-binding proteins in human osteoarthritic cartilage detected by immunohistochemistry and in situ hybridization, Osteoarthritis and Cartilage, 13, 439, 10.1016/j.joca.2004.12.006

De Ceuninck, 2004, Pharmacological disruption of insulin-like growth factor 1 binding to IGF-binding proteins restores anabolic responses in human osteoarthritic chondrocytes, Arthritis Research and Therapy, 6, R393, 10.1186/ar1201

Smeets, 2006, A novel role for SOCS3 in cartilage destruction via induction of chondrocyte desnesitization towards IGF-1, Arthritis and Rheumatism, 54, 1518, 10.1002/art.21752

Wang, 2003, Insulin-like growth factor 1-induced interleukin-1 receptor II overrides the activity of interleukin-1 and controls the homeostasis of the extracellular matrix of cartilage, Arthritis and Rheumatism, 48, 1281, 10.1002/art.11061

Takahashi, 2005, Elucidation of IL-1/TGF-beta interactions in mouse chondrocyte cell line by genome-wide gene expression, Osteoarthritis and Cartilage, 13, 426, 10.1016/j.joca.2004.12.010

Moulharat, 2004, Effects of transforming growth factor-beta on aggrecanase production and proteoglycan degradation by human chondrocytes in vitro, Osteoarthritis and Cartilage, 12, 296, 10.1016/j.joca.2003.11.009

Kaiser, 2004, Bone morphogenetic protein and transforming growth factor beta inhibitory Smads 6 and 7 are expressed in human adult normal and osteoarthritic cartilage in vivo and are differentially regulated in vitro by interleukin-1beta, Arthritis and Rheumatism, 50, 3535, 10.1002/art.20750

Blaney Davidson, 2006, Expression of TGF-beta and the TGF-beta signaling molecule SMAD-2P in spontaneous and instability-induced osteoarthritis. Role in cartilage degradation, chondrogenesis and osteophyte formation, Annals of the Rheumatic Diseases, 10.1136/ard.2005.045971

Goldring, 2006, The control of chondrogenesis, Journal of Cellular Biochemistry, 97, 33, 10.1002/jcb.20652

Gruber, 2001, Effects of cartilage-derived morphogenetic proteins and osteogenic protein-1 on osteochondrogenic differentiation of periosteum-derived cells, Endocrinology, 142, 2087, 10.1210/en.142.5.2087

Majumdar, 2001, BMP-2 and BMP-9 promotes chondrogenic differentiation of human multipotential mesenchymal cells and overcomes the inhibitory effect of IL-1, Journal of Cellular Physiology, 189, 275, 10.1002/jcp.10025

Chubinskaya, 2003, Regulation of osteogenic proteins by chondrocytes, The International Journal of Biochemistry and Cell Biology, 35, 1323, 10.1016/S1357-2725(03)00035-9

Grunder, 2004, Bone morphogenetic protein (BMP)-2 enhances the expression of type II collagen and aggrecan in chondrocytes embedded in alginate beads, Osteoarthritis and Cartilage, 12, 559, 10.1016/j.joca.2004.04.001

Ornitz, 2005, FGF signaling in the developing endochondral skeleton, Cytokine and Growth Factor Reviews, 16, 205, 10.1016/j.cytogfr.2005.02.003

Trippel, 2004, Growth factor inhibition: potential role in the etiopathogenesis of osteoarthritis, Clinical Orthopaedics and Related Research, 427, S47, 10.1097/01.blo.0000144973.09363.a5

Vincent, 2002, Basic FGF mediates an immediate response of articular cartilage to mechanical injury, Proceedings of the National Academy of Sciences of the USA, 99, 8259, 10.1073/pnas.122033199

Vincent, 2004, Basic fibroblast growth factor mediates transduction of mechanical signals when articular cartilage is loaded, Arthritis and Rheumatism, 50, 526, 10.1002/art.20047

Ellsworth, 2002, Fibroblast growth factor-18 is a trophic factor for mature chondrocytes and their progenitors, Osteoarthritis and Cartilage, 10, 308, 10.1053/joca.2002.0514

Au, 2004, Evaluation of thermoreversible polymers containing fibroblast growth factor 9 (FGF-9) for chondrocyte culture, Journal of Biomedical Materials Research A, 69, 367, 10.1002/jbm.a.20132

Shimoaka, 2002, Regulation of osteoblast, chondrocyte, and osteoclast functions by fibroblast growth factor (FGF)-18 in comparison with FGF-2 and FGF-10, The Journal of Biological Chemistry, 277, 7493, 10.1074/jbc.M108653200

Moore, 2005, Fibroblast growth factor-18 stimulates chondrogenesis and cartilage repair in a rat model of injury-induced osteoarthritis, Osteoarthritis and Cartilage, 13, 623, 10.1016/j.joca.2005.03.003

Solomon, 2005, Selective cyclooxygenase 2 inhibitors and cardiovascular events, Arthritis and Rheumatism, 52, 1968, 10.1002/art.21132

McAlindon, 2005, Nutritional factors and osteoarthritis: recent developments, Current Opinion in Rheumatology, 17, 647

Uitterlinden, 2005, Glucosamine decreases expression of anabolic and catabolic genes in human osteoarthritic cartilage explants, Osteoarthritis and Cartilage, 14, 250, 10.1016/j.joca.2005.10.001

Clegg, 2005, The efficacy of glucosamine and chondroitin sulfate in patients with painful knee osteoarthritis (OA): the glucosamine/chondroitin arthritis intervention trial (GAIT), Arthritis and Rheumatism, 52, S256

Braddock, 2004, Targeting IL-1 in inflammatory disease: new opportunities for therapeutic intervention, Nature Reviews. Drug Discovery, 3, 330, 10.1038/nrd1342

Murphy, 2005, What are the roles of metalloproteinases in cartilage and bone damage?, Annals of the Rheumatic Diseases, 64, iv44, 10.1136/ard.2005.042465

Brandt, 2005, Effects of doxycycline on progression of osteoarthritis: results of a randomized, placebo-controlled, double-blind trial, Arthritis and Rheumatism, 52, 2015, 10.1002/art.21122

Boyle, 2001, Anti-inflammatory effects of ABT-702, a novel non-nucleoside adenosine kinase inhibitor, in rat adjuvant arthritis, The Journal of Pharmacology and Experimental Therapeutics, 296, 495

Chevalier, 2005, Safety study of intraarticular injection of interleukin 1 receptor antagonist in patients with painful knee osteoarthritis: a multicenter study, The Journal of Rheumatology, 32, 1317

Frisbie, 2002, Treatment of experimental equine osteoarthritis by in vivo delivery of the equine interleukin-1 receptor antagonist gene, Gene Therapy, 9, 12, 10.1038/sj.gt.3301608

Glasson, 2005, Identification of targets through histologic evaluation of osteoarthritis in knockout mice, Osteoarthritis and Cartilage, 13, S3

Rudolphi, 2003, Pralnacasan, an inhibitor of interleukin-1beta converting enzyme, reduces joint damage in two murine models of osteoarthritis, Osteoarthritis and Cartilage, 11, 738, 10.1016/S1063-4584(03)00153-5

Blom, 2004, Synovial lining macrophages mediate osteophyte formation during experimental osteoarthritis, Osteoarthritis and Cartilage, 12, 627, 10.1016/j.joca.2004.03.003

de Hooge, 2005, Male IL-6 gene knock out mice developed more advanced osteoarthritis upon aging, Osteoarthritis and Cartilage, 13, 66, 10.1016/j.joca.2004.09.011

Keystone, 2003, Abandoned therapies and unpublished trials in rheumatoid arthritis, Current Opinion in Rheumatology, 15, 253, 10.1097/00002281-200305000-00012

Berenbaum, 2004, Signaling transduction: target in osteoarthritis, Current Opinion in Rheumatology, 16, 616, 10.1097/01.bor.0000133663.37352.4a

Malemud, 2004, Protein kinases in chondrocyte signaling and osteoarthritis, Clinical Orthopaedics and Related Research, 427, S145, 10.1097/01.blo.0000143802.41885.50

Fanning, 2003, Mechanical regulation of mitogen-activated protein kinase signaling in articular cartilage, The Journal of Biological Chemistry, 278, 50940, 10.1074/jbc.M305107200

Fitzgerald, 2004, Mechanical compression of cartilage explants induces multiple time-dependent gene expression patterns and involves intracellular calcium and cyclic AMP, The Journal of Biological Chemistry, 279, 19502, 10.1074/jbc.M400437200

Agarwal, 2004, Role of NF-kappaB transcription factors in antiinflammatory and proinflammatory actions of mechanical signals, Arthritis and Rheumatism, 50, 3541, 10.1002/art.20601

Roshak, 2002, Small-molecule inhibitors of NF-kappaB for the treatment of inflammatory joint disease, Current Opinion in Pharmacology, 2, 316, 10.1016/S1471-4892(02)00165-0

Hammaker, 2003, Signal transduction networks in rheumatoid arthritis, Annals of the Rheumatic Diseases, 62, ii86

McIntyre, 2003, A highly selective inhibitor of I kappa B kinase, BMS-345541, blocks both joint inflammation and destruction in collagen-induced arthritis in mice, Arthritis and Rheumatism, 48, 2652, 10.1002/art.11131

Pattoli, 2005, Collagen and aggrecan degradation is blocked in interleukin-1-treated cartilage explants by an inhibitor of IkappaB kinase through suppression of metalloproteinase expression, The Journal of Pharmacology and Experimental Therapeutics, 315, 382, 10.1124/jpet.105.087569

Pargellis, 2003, Inhibitors of p38 mitogen-activated protein kinase for the treatment of rheumatoid arthritis, Current Opinion in Investigational Drugs, 4, 566

Badger, 2001, Disease-modifying activity of SB 273005, an orally active, nonpeptide alphavbeta3 (vitronectin receptor) antagonist, in rat adjuvant-induced arthritis, Arthritis and Rheumatism, 44, 128, 10.1002/1529-0131(200101)44:1<128::AID-ANR17>3.0.CO;2-M

Nishikawa, 2003, Prevention of the onset and progression of collagen-induced arthritis in rats by the potent p38 mitogen-activated protein kinase inhibitor FR167653, Arthritis and Rheumatism, 48, 2670, 10.1002/art.11227

Zwerina, 2006, Activation of p38 MAPK is a key step in tumor necrosis factor-mediated inflammatory bone destruction, Arthritis and Rheumatism, 54, 463, 10.1002/art.21626

Dominguez, 2005, p38 MAP kinase inhibitors: many are made, but few are chosen, Current Opinion in Drug Discovery and Development, 8, 421

Pramanik, 2003, p38 isoforms have opposite effects on AP-1-dependent transcription through regulation of c-Jun. The determinant roles of the isoforms in the p38 MAPK signal specificity, The Journal of Biological Chemistry, 278, 4831, 10.1074/jbc.M207732200

Beier, 2005, Cell-cycle control and the cartilage growth plate, Journal of Cellular Physiology, 202, 1, 10.1002/jcp.20111

Mavunkel, 2003, Indole-based heterocyclic inhibitors of p38alpha MAP kinase: designing a conformationally restricted analogue, Bioorganic and Medicinal Chemistry Letters, 13, 3087, 10.1016/S0960-894X(03)00653-X

Wrobleski, 2005, Structural comparison of p38 inhibitor-protein complexes: a review of recent p38 inhibitors having unique binding interactions, Current Topics in Medicinal Chemistry, 5, 1005, 10.2174/1568026054985894

Bogoyevitch, 2004, Targeting the JNK MAPK cascade for inhibition: basic science and therapeutic potential, Biochimica et Biophysica Acta, 1697, 89, 10.1016/j.bbapap.2003.11.016

Bogoyevitch, 2005, Therapeutic promise of JNK ATP-noncompetitive inhibitors, Trends in Molecular Medicine, 11, 232, 10.1016/j.molmed.2005.03.005

Bennett, 2001, SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase, Proceedings of the National Academy of Sciences of the USA, 98, 13681, 10.1073/pnas.251194298

Clancy, 2001, Activation of stress-activated protein kinase in osteoarthritic cartilage: evidence for nitric oxide dependence, Osteoarthritis and Cartilage, 9, 294, 10.1053/joca.2000.0388

Loeser, 2003, Fibronectin fragment activation of proline-rich tyrosine kinase PYK2 mediates integrin signals regulating collagenase-3 expression by human chondrocytes through a protein kinase C-dependent pathway, The Journal of Biological Chemistry, 278, 24577, 10.1074/jbc.M304530200

Ahmed, 2003, Phenyl N-tert-butylnitrone down-regulates interleukin-1 beta-stimulated matrix metalloproteinase-13 gene expression in human chondrocytes: suppression of c-Jun NH2-terminal kinase, p38-mitogen-activated protein kinase and activating protein-1, The Journal of Pharmacology and Experimental Therapeutics, 305, 981, 10.1124/jpet.102.048611

Pelletier, 2003, In vivo selective inhibition of mitogen-activated protein kinase kinase 1/2 in rabbit experimental osteoarthritis is associated with a reduction in the development of structural changes, Arthritis and Rheumatism, 48, 1582, 10.1002/art.11014

Cha, 2006, The novel Syk inhibitor R406 blocks JNK-mediated gene expression in synoviocytes, The Journal of Pharmacology and Experimental Therapeutics, 10.1124/jpet.105.097436

Hunziker, 2002, Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects, Osteoarthritis and Cartilage, 10, 432, 10.1053/joca.2002.0801

Brittberg, 1994, Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation, The New England Journal of Medicine, 331, 889, 10.1056/NEJM199410063311401

Knutsen, 2004, Autologous chondrocyte implantation compared with microfracture in the knee. A randomized trial, The Journal of Bone and Joint Surgery. American Volume, 86-A, 455, 10.2106/00004623-200403000-00001

Lories, 2005, Bone morphogenetic protein signaling in joint homeostasis and disease, Cytokine and Growth Factor Reviews, 16, 287, 10.1016/j.cytogfr.2005.02.009

Seeherman, 2005, Delivery of bone morphogenetic proteins for orthopedic tissue regeneration, Cytokine and Growth Factor Reviews, 16, 329, 10.1016/j.cytogfr.2005.05.001

Sellers, 2000, Repair of articular cartilage defects one year after treatment with recombinant human bone morphogenetic protein-2 (rhBMP-2), The Journal of Bone and Joint Surgery. American Volume, 82, 151, 10.2106/00004623-200002000-00001

Louwerse, 2000, Use of recombinant human osteogenic protein-1 for the repair of subchondral defects in articular cartilage in goats, Journal of Biomedical Materials Research, 49, 506, 10.1002/(SICI)1097-4636(20000315)49:4<506::AID-JBM9>3.0.CO;2-A

Jelic, 2001, Regeneration of articular cartilage chondral defects by osteogenic protein-1 (bone morphogenetic protein-7) in sheep, Growth Factors, 19, 101, 10.3109/08977190109001079

Katayama, 2004, Repair of articular cartilage defects in rabbits using CDMP1 gene-transfected autologous mesenchymal cells derived from bone marrow, Rheumatology (Oxford), 43, 980, 10.1093/rheumatology/keh240

Gooch, 2002, Bone morphogenetic proteins-2, -12, and -13 modulate in vitro development of engineered cartilage, Tissue Engineering, 8, 591, 10.1089/107632702760240517

Hills, 2005, Bone morphogenetic protein 9 is a potent anabolic factor for juvenile bovine cartilage, but not adult cartilage, Journal of Orthopaedic Research, 23, 611, 10.1016/j.orthres.2004.12.009

Tcacencu, 2005, Effect of recombinant human BMP-2 on the repair of cricoid cartilage defects in young and adult rabbits: a comparative study, International Journal of Pediatric Otorhinolaryngology, 69, 1239, 10.1016/j.ijporl.2005.03.026

Zoricic, 2003, Expression of bone morphogenetic proteins and cartilage-derived morphogenetic proteins during osteophyte formation in humans, Journal of Anatomy, 202, 269, 10.1046/j.1469-7580.2003.00158.x

Hunziker, 2001, Chondrogenesis in cartilage repair is induced by members of the transforming growth factor-beta superfamily, Clinical Orthopaedics and Related Research, 391, S171, 10.1097/00003086-200110001-00017

Scharstuhl, 2002, Inhibition of endogenous TGF-beta during experimental osteoarthritis prevents osteophyte formation and impairs cartilage repair, The Journal of Immunology, 169, 507, 10.4049/jimmunol.169.1.507

Scharstuhl, 2003, Reduction of osteophyte formation and synovial thickening by adenoviral overexpression of transforming growth factor beta/bone morphogenetic protein inhibitors during experimental osteoarthritis, Arthritis and Rheumatism, 48, 3442, 10.1002/art.11328

Friedenstein, 1966, Osteogenesis in transplants of bone marrow cells, Journal of Embryology and Experimental Morphology, 16, 381

Tuan, 2004, Biology of developmental and regenerative skeletogenesis, Clinical Orthopaedics and Related Research, 427, S105, 10.1097/01.blo.0000143560.41767.ee

Barry, 2004, Mesenchymal stem cells: clinical applications and biological characterization, International Journal of Biochemistry and Cell Biology, 36, 568, 10.1016/j.biocel.2003.11.001

Caplan, 2005, Review: mesenchymal stem cells: cell-based reconstructive therapy in orthopedics, Tissue Engineering, 11, 1198, 10.1089/ten.2005.11.1198

Magne, 2005, Mesenchymal stem cell therapy to rebuild cartilage, Trends in Molecular Medicine, 11, 519, 10.1016/j.molmed.2005.09.002

Urist, 1965, Bone: formation by autoinduction, Science, 150, 893, 10.1126/science.150.3698.893

Huang, 2005, Chondrogenic potential of progenitor cells derived from human bone marrow and adipose tissue: a patient-matched comparison, Journal of Orthopaedic Research, 23, 1383, 10.1016/j.orthres.2005.03.008.1100230621

Palmer, 2005, Gene-induced chondrogenesis of primary mesenchymal stem cells in vitro, Molecular Therapy, 12, 219, 10.1016/j.ymthe.2005.03.024

Ikeda, 2004, The combination of SOX5, SOX6, and SOX9 (the SOX trio) provides signals sufficient for induction of permanent cartilage, Arthritis and Rheumatism, 50, 3561, 10.1002/art.20611

Tew, 2005, Retroviral transduction with SOX9 enhances re-expression of the chondrocyte phenotype in passaged osteoarthritic human articular chondrocytes, Osteoarthritis and Cartilage, 13, 80, 10.1016/j.joca.2004.10.011

Goldring, 2006, Are bone morphogenetic proteins effective inducers of cartilage repair? Ex vivo transduction of muscle-derived stem cells, Arthritis and Rheumatism, 54, 387, 10.1002/art.21756

Kuroda, 2006, Cartilage repair using bone morphogenetic protein 4 and muscle-derived stem cells, Arthritis and Rheumatism, 54, 433, 10.1002/art.21632

El Hajjaji, 2004, Treatment with calcitonin prevents the net loss of collagen, hyaluronan and proteoglycan aggregates from cartilage in the early stages of canine experimental osteoarthritis, Osteoarthritis and Cartilage, 12, 904, 10.1016/j.joca.2004.08.005

Bagger, 2005, Oral salmon calcitonin induced suppression of urinary collagen type II degradation in postmenopausal women: a new potential treatment of osteoarthritis, Bone, 37, 425, 10.1016/j.bone.2005.04.032

Spector, 2003, Bisphosphonates: potential therapeutic agents for disease modification in osteoarthritis, Aging Clinical and Experimental Research, 15, 413, 10.1007/BF03327362

Ham, 2004, Effects of estrogen replacement therapy on bone turnover in subchondral bone and epiphyseal metaphyseal cancellous bone of ovariectomized cynomolgus monkeys, Journal of Bone and Mineral Research, 19, 823, 10.1359/jbmr.040309

Radin, 1986, Role of subchondral bone in the initiation and progression of cartilage damage, Clinical Orthopaedics and Related Research, 213, 34, 10.1097/00003086-198612000-00005

Burr, 2004, Anatomy and physiology of the mineralized tissues: role in the pathogenesis of osteoarthrosis, Osteoarthritis and Cartilage, 12, S20, 10.1016/j.joca.2003.09.016

Buckland-Wright, 2004, Subchondral bone changes in hand and knee osteoarthritis detected by radiography, Osteoarthritis and Cartilage, 12, S10, 10.1016/j.joca.2003.09.007

Mrosek, 2006, Subchondral bone trauma causes cartilage matrix degeneration: an immunohistochemical analysis in a canine model, Osteoarthritis and Cartilage, 14, 171, 10.1016/j.joca.2005.08.004

Bailey, 2004, Biochemical and mechanical properties of subchondral bone in osteoarthritis, Biorheology, 41, 349

Wang, 2004, Regulation of MMP-13 expression by RUNX2 and FGF2 in osteoarthritic cartilage, Osteoarthritis and Cartilage, 12, 963, 10.1016/j.joca.2004.08.008

Komuro, 2001, The osteoprotegerin/receptor activator of nuclear factor kappaB/receptor activator of nuclear factor kappaB ligand system in cartilage, Arthritis and Rheumatism, 44, 2768, 10.1002/1529-0131(200112)44:12<2768::AID-ART464>3.0.CO;2-I

Kishimoto, 2006, Expression profile of genes related to osteoclastogenesis in mouse growth plate and articular cartilage, Histochemistry and Cell Biology, 125, 593, 10.1007/s00418-005-0103-z

Pettit, 2001, TRANCE/RANKL knockout mice are protected from bone erosion in a serum transfer model of arthritis, American Journal of Pathology, 159, 1689, 10.1016/S0002-9440(10)63016-7

Loughlin, 2004, Functional variants within the secreted frizzled-related protein 3 gene are associated with hip osteoarthritis in females, Proceedings of the National Academy of Sciences of the USA, 101, 9757, 10.1073/pnas.0403456101

Lane, 2006, Frizzled related protein variants are risk factors for hip osteoarthritis, Arthritis and Rheumatism, 54, 1246, 10.1002/art.21673

James, 2000, FrzB-2: a human secreted frizzled-related protein with a potential role in chondrocyte apoptosis, Osteoarthritis and Cartilage, 8, 452, 10.1053/joca.1999.0321

Tamamura, 2005, Developmental regulation of Wnt/beta-catenin signals is required for growth plate assembly, cartilage integrity, and endochondral ossification, The Journal of Biological Chemistry, 280, 19185, 10.1074/jbc.M414275200

Ijiri, 2005, A novel role for GADD45beta as a mediator of MMP-13 gene expression during chondrocyte terminal differentiation, The Journal of Biological Chemistry, 280, 38544, 10.1074/jbc.M504202200

Guevremont, 2003, Human adult chondrocytes express hepatocyte growth factor (HGF) isoforms but not HgF: potential implication of osteoblasts on the presence of HGF in cartilage, Journal of Bone and Mineral Research, 18, 1073, 10.1359/jbmr.2003.18.6.1073

Massicotte, 2006, Modulation of insulin-like growth factor 1 levels in human osteoarthritic subchondral bone osteoblasts, Bone, 38, 333, 10.1016/j.bone.2005.09.007

Haywood, 2003, Inflammation and angiogenesis in osteoarthritis, Arthritis and Rheumatism, 48, 2173, 10.1002/art.11094

Honorati, 2006, Interleukin-17, a regulator of angiogenic factor release by synovial fibroblasts, Osteoarthritis and Cartilage, 14, 345, 10.1016/j.joca.2005.10.004

Pufe, 2005, The influence of biomechanical parameters on the expression of VEGF and endostatin in the bone and joint system, Annals of Anatomy, 187, 461, 10.1016/j.aanat.2005.06.008

Pfander, 2005, Hypoxia and HIF-1alpha in osteoarthritis, International Orthopaedics, 29, 6, 10.1007/s00264-004-0618-2

François, 2006, Peroxisome proliferator-activated receptor-α-activation pathway potentiates interleukin-1 receptor antagonist production in cytokine-treated chondrocytes, Arthritis and Rheumatism, 54, 1233, 10.1002/art.21728

Ling, 2004, The chitinase 3-like protein human cartilage glycoprotein 39 inhibits cellular responses to the inflammatory cytokines interleukin-1 and tumour necrosis factor-alpha, Biochemical Journal, 380, 651, 10.1042/bj20040099

Recklies, 2005, Inflammatory cytokines induce production of chitinase-3-like protein 1 by articular chondrocytes, The Journal of Biological Chemistry, 280, 41213, 10.1074/jbc.M510146200

Yammani RR, Carlson CS, Bresnick AR et al. S100A4 activates receptor for advanced glycation end-products (RAGE) signaling and stimulates matrix metalloproteinase-13 production in human articular chondrocytes. Arthritis and Rheumatism [in press].

Milner, 2006, Fibroblast activation protein alpha is expressed by chondrocytes following a pro-inflammatory stimulus and is elevated in osteoarthritis, Arthritis Research and Therapy, 8, R23, 10.1186/ar1877

Dumond, 2003, Evidence for a key role of leptin in osteoarthritis, Arthritis and Rheumatism, 48, 3118, 10.1002/art.11303