https://scholars.lib.ntu.edu.tw/handle/123456789/159907
DC Field | Value | Language |
---|---|---|
dc.contributor | 吳忠勳 | en |
dc.contributor | 臺灣大學:分子醫學研究所 | zh_TW |
dc.contributor.author | 謝昌訓 | zh |
dc.contributor.author | Hsieh, Chang-Hsun | en |
dc.creator | 謝昌訓 | zh |
dc.creator | Hsieh, Chang-Hsun | en |
dc.date | 2007 | en |
dc.date.accessioned | 2007-11-26T01:33:36Z | - |
dc.date.accessioned | 2018-07-09T01:09:37Z | - |
dc.date.available | 2007-11-26T01:33:36Z | - |
dc.date.available | 2018-07-09T01:09:37Z | - |
dc.date.issued | 2007 | - |
dc.identifier | en-US | en |
dc.identifier.uri | http://ntur.lib.ntu.edu.tw//handle/246246/51378 | - |
dc.description.abstract | 背景:軟骨組織的自我修復以及再生能力皆十分的不足,成年人比年輕人的軟骨組織自我修復能力更是低弱。隨著年紀的增長:軟骨組織內的自由基會增多、軟骨細胞數目會減少以及軟骨細胞之間的基質變少使得軟骨組織漸漸稀薄,導致退化性關節炎的產生。基於上述原因,軟骨細胞的特性一直被探討研究以期能在組織工程與臨床上有所應用。(一)由於核磁共振儀為非入侵的醫療評估方式,目前在臨床醫學的使用極為普遍,包括腦部斷層掃瞄、腫瘤追蹤及外科復原評估等等。然而,在近幾年的文獻中不斷探討高磁場環境與無線電電波對細胞、生理和心理的影響,包括c-jun、c-fos基因的表現,鈣離子濃度的增加以及幽閉空間恐懼症等等,顯示磁場環境與無線電電波會對細胞有某種程度的影響,而這方面的研究一直未有明確的結果。所以我們在第一部份先探討高磁場環境下對於軟骨細胞的影響。(二)原子力顯微鏡是目前探討奈米世界的最佳工具。主要是利用探針與雷射的折射角度變化來觀察活著細胞的奈米結構,並可監測細胞膜的物理特性,如黏著力和硬度。所以,我們利用原子力顯微鏡來探討正常(成年人)軟骨細胞與退化性關節炎(老年人)軟骨細胞其細胞膜物理特質的差異性。(三)間葉幹細胞有分化成不同種類細胞的能力,如可以分化成脂肪細胞、肌肉細胞、骨細胞與軟骨細胞。而軟骨細胞在長期的單層細胞培養系統中之初代培養下,其軟骨細胞的特性會漸漸消失並轉型成纖維細胞,所以我們在第三部分建立其間葉幹細胞的分化系統並觀察軟骨細胞的立體培養系統下的生長情況。 研究方法:(一)我們利用3T 強度的核磁共振儀製造高磁場環境,觀察高磁場對軟骨細胞的生長、鈣離子濃度變化與蛋白質表現變化的差異性。另外,建立迷你豬(李宋豬)的軟骨修復評估之動物模式,利用組織切片染色觀察高磁場環境對於軟骨修復之影響。(二)我們利用原子力顯微鏡直接觀測軟骨細胞的細胞膜之物理特性,如黏著力和硬度。另外,利用流式細胞儀檢測軟骨細胞上蛋白質的表現量來佐證原子力顯微鏡觀測的結果。(三)我們建立間葉幹細胞的多型性分化能力,並利用免疫染色來檢驗各個分化細胞型態的成果。此外我們利用反轉錄聚合酶連鎖反應來觀察在單層細胞培養之繼代培養系統下軟骨細胞特性的變化。我們也利用掃瞄式電子顯微鏡來觀察軟骨細胞在聚乳酸與聚羥基乙酸材質所構成的立體培養環境之情況。 結果與討論:(一)在核磁共振儀環境中,軟骨細胞會因為高磁場或是高磁場加上無線電能量的刺激下而造成細胞內鈣離子濃度升高和誘導細胞凋亡相關蛋白質的大量表現進而使軟骨細胞進入細胞程式化死亡。另外在豬隻軟骨修復與評估的計畫中,相同的實驗條件下,利用核磁共振評估與沒有利用核磁共振評估的豬隻相較下發現,使用核磁共振之豬隻軟骨修復情況極為不好,修復位置(即原造成損傷位置)有一嚴重的凹陷損傷。推測原因可能在軟骨修復過程中,因為暴露在核磁共振環境下造成細胞死亡或細胞轉性而影響到軟骨之修復。(二)透過原子力顯微鏡的測量,正常(成年人)軟骨細胞的細胞表面起伏變化比退化性關節炎(老年人)之軟骨細胞劇烈。正常(成年人)軟骨細胞其細胞膜的黏著度與硬度均大於退化性關節炎(老年人)之軟骨細胞。另外,我們也發現正常(成年人)軟骨細胞其表面蛋白質表現量(integrin beta1 and type II collagen)也明顯比退化性關節炎(老年人)之軟骨細胞表現量多。這可以建立一觀測細胞膜物理特質之系統,用來觀測軟骨細胞隨著年紀增長之健康度變化。(三)我們成功地建立利用間葉幹細胞分化成其他細胞型態之系統。另外,我們也觀察到軟骨細胞在單層細胞培養下,約第八代便會失去其軟骨細胞之特質。而軟骨細胞在聚乳酸與聚羥基乙酸材質所構成的立體培養環境下生長,會誘導軟骨細胞分泌更多的細胞外間質。 | zh_TW |
dc.description.abstract | Background: The proliferation and self-repair of articular cartilage are both poor. In fact, a number of age-related changes occur in the articular cartilage, including the free radical increase, a decrease in the number of chondrocytes and an increase in the degradation of matrix components. Such an age-related degeneration of articular cartilage could be a major risk factor for the development of osteoarthritis. Therefore, a lot of medical researches focused on the characters of chondrocytes in tissue engineering and clinic research. For instance, (1) As the MRI is a non-invasive physical assessment method, it is prevailing in clinic, including brain CT, tumor tracing, and assessment of surgery recovery…etc. In recent years, many papers discuss about the influence of high magnetic field or radiation on the cell, physiology and psychology, including expression of c-jun and c-fos genes, Ca2+ flux change, particularly Ca2+ entry from the extracellular environment through the plasma membrane, and induction of cloustrophobia syndrome…etc. Studies with cellular systems using different exposure setups, exposure durations, amplitudes, frequencies and wave forms indicate that biological effects of magnetic fields on cellular systems are at hand, but there is no definite conclusion in this field. In the first aim, we want to monitor the effect of the high magnetic field on human chondrocytes. (2) Atomic force microscope (AFM) permits the characterization of biologic samples ranging from a single molecules to whole cells (nanometers to micrometers), it is a powerful tool for exploring the shape of a single cell, the properties of a cellular membrane, or the interaction of intermolecular forces, such as adhesion force and stiffness. The second aim of this study is to use AFM technique to differentiate the mechanical behavior of the chondrocytes between the young modulus (normal) and the old modulus (OA). (3) Mesenchymal stem cells have multi-potential differentiation capacities, such as fat, muscle, bone and cartilage. In addition, primary culture of chondrocytes tend to lose the chondro-property and de-differentiation in monolayer culture condition during subculture. The third aim is to evaluate the characterization of MSCs differential capacities and establishing the 3D culture system for chondrocytes in vitro. Method: (1) The 3T magnetic field was provided by the machine of Magnetic Resonance Imaging. The human chondrocytes were directly exposed to a 3-tesla (T) magnetic field (MF group) or a 3-T static magnetic field plus 125.3 MHz radio frequency (MF+RF group), and cell proliferation, apoptosis, cytosolic Ca2+ ([Ca2+]i) fluxes and expression of the apoptosis-related proteins of the treated cells were examined to assess the effects of the treatments. In the pig study, we examined the effects of the treatments on the recovery of surgically damaged pig knees. (2) We used AFM to observe a single chondrocyte cell directly and measured the dimensions of the cells. In addition, the receptors of cellular membrane were monitored by FACS. (3) The MSCs were isolated from human bone marrow. The MSCs were induced to adipogenesis, myogenesis, osteogenesis and chondrogenesis separately by respective inducers. The differentiated cell lineages were confirmed by specific markers expression by immunochemical staining. In addition, the RT-PCR system was applied for monitoring the property of chondrocytes in monolayer culture condition during subculture. Besides, chondrocytes which were seeded in the PGA/PLA scaffold was evaluated by using SEM observation. Results and discussions: (1) A 3-T static magnetic field and radio frequency suppressed cell growth and induced apoptosis through p53, p21, p27 and Bax protein expression. In the pig model, we found that MRI surveillance had a deleterious effect on the recovery of the damaged knee cartilage. Magnetic strength, with or without concurrent radio frequency, suppressed chondrocyte growth in vitro and affected recovery of damaged knee cartilage in vivo in the pig model. The possible reason is chondrocytes exposing to the high magnetic field inducing cell apoptosis or cell transformation in the cartilage repair process. (2) The AFM revealed differences in the sizes and structures between the young modulus (normal) and the old modulus (OA). These findings suggested that the mechanical properties of normal chondrocytes substantially differed from those of OA chondrocytes. This new approach could be a useful technique for investigating age-related changes in the properties of human chondrocytes. (3) The MSCs from human bone marrow could differentiate into adipogenesis, myogenesis, osteogenesis and chondrogenesis processes. The morphology of human chondrocytes can be maintained after six passages both in petri dish and on scaffold but the cells were easily to be transformed to fibroblasts after eight passages. The scaffold laminated by PLA-coated PGA fiber was suitable for chondrocytes growth and showed better cell attachment under SEM investigation. | en |
dc.description.tableofcontents | 中文摘要........................................................................................................................1 英文摘要........................................................................................................................3 Literature review……………………………………………………………………....6 Tissue engineering………………………………………………………………….6 Mesenchymal stem cells……………………………………………………………6 Scaffolds……………………………………………………………………………7 Signaling……………………………………………………………………………8 chondrocytes………………………………………………………………………..9 Magnetic resonance imaging……………………………………………………..11 Radio frequency…………………………………………………………………12 Cell death program, apoptosis……………………………………………………13 Calcium ions concentration……………………………………………………….17 Atomic force microscopy…………………………………………………………17 Force-distance curve………………………………………………………………21 Part 1: Deleterious Effects of MRI on Chondrocytes………………………………23 Abstract……………………………………………………………………………24 Introduction………………………………………………………………………25 Materials and Methods……………………………………………………………27 Isolations of human chondrocytes……………………………………………27 Magnetic field application……………………………………………………27 Cell proliferation assay………………………………………………………28 Flow cytometry assay………………………………………………………28 DNA fragmentation assay……………………………………………………29 Intracellular calcium concentration measurement……………………………29 Western blot analysis…………………………………………………………30 Lee-Sung pig animal model…………………………………………………31 Histochemical staining………………………………………………………31 Data analysis……………………………………………….............................32 Results……………………………………………………………………………33 3-T magnetic field and radio frequency influence on cell proliferation and cell apoptosis…………………….………………………………………33 DNA fragmentation after magnetic exposure………………………………33 Effects on intracellular calcium concentration………………………………34 Effects on gene expression…………………………………………………...34 Effects of MRI on pig knee repair……………………………………………35 Discussion…………………………………………………………………………37 Part II: Surface ultrastructure and mechanical property of human chondrocyte revealed by Atomic Force Microscopy………………………………………………41 Abstract……………………………………………………………………………42 Introduction………………………………………………………………………43 Materials and Methods…………………………………………………………....46 Chamicals…………………………………………………………………….46 Isolation of Human Chondrocytes and Cell Immobilization…………………46 Atomic Force Microscopy……………………………………………………47 Single-Cell AFM Measurement…………………………………...…………47 Adhesion Force and Stiffness Measurements…………………………….......49 Flow cytometry assay………………………………………………………...50 Results…………………………………………………………………………….52 AFM Imaging of Chondrocytes………………………………………………52 Force-Curve Analysis of Chondrocytes……………………………………52 Mechanical Properties of Chondrocytes……………………………………...53 The cell-associated matrix of chondrocytes…………………………………53 Discussion……………………………………………………………………….55 Part III: Tissue Engineering: Chondrocytes regeneration……………………………59 Abstract……………………………………………………………………………60 Introduction……………………………………………………………………….62 Materials and Methods……………………………………………………………64 Isolations of human bone marrow and chondrocytes………………………64 Adipogenic differentiation……………………………………………………64 Myogenic differentiation……………………………………………………..65 Osteogenic differentiation……………………………………………………65 Chondrogenic differentiation…………………………………………………65 Oil-Red-O staining…………………………………………………………...66 Immunohistochemical staining………………………………………………66 RNA Extraction and RT-PCR………………………………………………67 PLA/PGA preparation………………………………………………………..67 SEM preparation……………………………………………………………...68 Results…………………………………………………………………………….69 MSCs differentiation potential characterization……………………………69 Characterization of human chondrocytes……………………………………70 Chondrocytes culture in PLA/PGA scaffold…………………………………70 Discussion…………………………………………………………………………72 Appendixes…………………………………………………………………………75 Figures…………………………………………………………………………….75 Tables…………………………………………………………………………….105 Research Publications……………………………………………………............107 Reference……………………………………………………………………………108 | zh_TW |
dc.language | en-US | en |
dc.language.iso | en_US | - |
dc.subject | 軟骨細胞 | en |
dc.subject | 核磁共振儀 | en |
dc.subject | 原子力顯微鏡 | en |
dc.subject | 黏著度 | en |
dc.subject | 硬度 | en |
dc.subject | 間葉幹細胞 | en |
dc.subject | 聚乳酸與聚羥基乙酸 | en |
dc.subject | chondrocytes, MRI | en |
dc.subject | AFM | en |
dc.subject | adhesion force | en |
dc.subject | stiffness | en |
dc.subject | MSCs and PLA/PGA | en |
dc.title | 軟骨細胞的分化、細胞表面之超微結構與高磁場環境對軟骨復原的影響之研究 | zh_TW |
dc.title | Differentiation of chondrocytes, characterization of cell surface of chondrocytes and deleterious effects of MRI on cartilage repair | en |
dc.type | other | en |
dc.relation.reference | 1. Hutmacher DW. Scaffold design and fabrication technologies for engineering tissues--state of the art and future perspectives. J Biomater Sci Polym Ed 2001; 12: 107-124. 2. Ripamonti U, Reddi AH. Tissue engineering, morphogenesis, and regeneration of the periodontal tissues by bone morphogenetic proteins. Crit Rev Oral Biol Med 1997; 8: 154-163. 3. Lee HS, Huang GT, Chiang H, Chiou LL, Chen MH, Hsieh CH, et al. Multipotential mesenchymal stem cells from femoral bone marrow near the site of osteonecrosis. Stem Cells 2003; 21: 190-199. 4. Prockop DJ. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 1997; 276: 71-74. 5. Chen MH, Lin S, Hsieh CH, Lee HS, Chiang H, Jiang CC. Identification and initial characterization of small cells in adult cartilage and bone marrow. J Formos Med Assoc 2004; 103: 264-273. 6. Sharma B, Elisseeff JH. Engineering structurally organized cartilage and bone tissues. Ann Biomed Eng 2004; 32: 148-159. 7. Gao J, Dennis JE, Muzic RF, Lundberg M, Caplan AI. The dynamic in vivo distribution of bone marrow-derived mesenchymal stem cells after infusion. Cells Tissues Organs 2001; 169: 12-20. 8. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284: 143-147. 9. Deng W, Obrocka M, Fischer I, Prockop DJ. In vitro differentiation of human marrow stromal cells into early progenitors of neural cells by conditions that increase intracellular cyclic AMP. Biochem Biophys Res Commun 2001; 282: 148-152. 10. Zhang X, Mitsuru A, Igura K, Takahashi K, Ichinose S, Yamaguchi S, et al. Mesenchymal progenitor cells derived from chorionic villi of human placenta for cartilage tissue engineering. Biochem Biophys Res Commun 2006; 340: 944-952. 11. Bickenbach JR. Isolation, characterization, and culture of epithelial stem cells. Methods Mol Biol 2005; 289: 97-102. 12. Huang JI, Beanes SR, Zhu M, Lorenz HP, Hedrick MH, Benhaim P. Rat extramedullary adipose tissue as a source of osteochondrogenic progenitor cells. Plast Reconstr Surg 2002; 109: 1033-1041; discussion 1042-1033. 13. Lee JA, Parrett BM, Conejero JA, Laser J, Chen J, Kogon AJ, et al. Biological alchemy: engineering bone and fat from fat-derived stem cells. Ann Plast Surg 2003; 50: 610-617. 14. Kim JW, Kim SY, Park SY, Kim YM, Kim JM, Lee MH, et al. Mesenchymal progenitor cells in the human umbilical cord. Ann Hematol 2004; 83: 733-738. 15. Jones EA, English A, Henshaw K, Kinsey SE, Markham AF, Emery P, et al. Enumeration and phenotypic characterization of synovial fluid multipotential mesenchymal progenitor cells in inflammatory and degenerative arthritis. Arthritis Rheum 2004; 50: 817-827. 16. Yang XC, Fan MW. [Identification and isolation of human dental pulp stem cells]. Zhonghua Kou Qiang Yi Xue Za Zhi 2005; 40: 244-247. 17. Beyer Nardi N, da Silva Meirelles L. Mesenchymal stem cells: isolation, in vitro expansion and characterization. Handb Exp Pharmacol 2006: 249-282. 18. Sotiropoulou PA, Perez SA, Salagianni M, Baxevanis CN, Papamichail M. Characterization of the optimal culture conditions for clinical scale production of human mesenchymal stem cells. Stem Cells 2006; 24: 462-471. 19. Bonab MM, Alimoghaddam K, Talebian F, Ghaffari SH, Ghavamzadeh A, Nikbin B. Aging of mesenchymal stem cell in vitro. BMC Cell Biol 2006; 7: 14. 20. Pajoohesh-Ganji A, Stepp MA. In search of markers for the stem cells of the corneal epithelium. Biol Cell 2005; 97: 265-276. 21. Stewart K, Monk P, Walsh S, Jefferiss CM, Letchford J, Beresford JN. STRO-1, HOP-26 (CD63), CD49a and SB-10 (CD166) as markers of primitive human marrow stromal cells and their more differentiated progeny: a comparative investigation in vitro. Cell Tissue Res 2003; 313: 281-290. 22. Ding S, Li L, Zhou C. [Novel scaffold materials for tissue engineering]. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2002; 19: 122-126. 23. Stock UA, Mayer JE, Jr. Tissue engineering of cardiac valves on the basis of PGA/PLA Co-polymers. J Long Term Eff Med Implants 2001; 11: 249-260. 24. Jain RA. The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices. Biomaterials 2000; 21: 2475-2490. 25. Athanasiou KA, Agrawal CM, Barber FA, Burkhart SS. Orthopaedic applications for PLA-PGA biodegradable polymers. Arthroscopy 1998; 14: 726-737. 26. Feve B. Adipogenesis: cellular and molecular aspects. Best Pract Res Clin Endocrinol Metab 2005; 19: 483-499. 27. Hoffmann A, Gross G. BMP signaling pathways in cartilage and bone formation. Crit Rev Eukaryot Gene Expr 2001; 11: 23-45. 28. Moore KA, Lemischka IR. Stem cells and their niches. Science 2006; 311: 1880-1885. 29. Hardingham TE, Fosang AJ. Proteoglycans: many forms and many functions. Faseb J 1992; 6: 861-870. 30. Eyre D. Collagen of articular cartilage. Arthritis Res 2002; 4: 30-35. 31. Shen G. The role of type X collagen in facilitating and regulating endochondral ossification of articular cartilage. Orthod Craniofac Res 2005; 8: 11-17. 32. Knudson CB, Knudson W. Cartilage proteoglycans. Semin Cell Dev Biol 2001; 12: 69-78. 33. Schwartz NB, Pirok EW, 3rd, Mensch JR, Jr., Domowicz MS. Domain organization, genomic structure, evolution, and regulation of expression of the aggrecan gene family. Prog Nucleic Acid Res Mol Biol 1999; 62: 177-225. 34. Lefebvre V, Smits P. Transcriptional control of chondrocyte fate and differentiation. Birth Defects Res C Embryo Today 2005; 75: 200-212. 35. Lefebvre V, Behringer RR, de Crombrugghe B. L-Sox5, Sox6 and Sox9 control essential steps of the chondrocyte differentiation pathway. Osteoarthritis Cartilage 2001; 9 Suppl A: S69-75. 36. Smits P, Li P, Mandel J, Zhang Z, Deng JM, Behringer RR, et al. The transcription factors L-Sox5 and Sox6 are essential for cartilage formation. Dev Cell 2001; 1: 277-290. 37. Smits P, Dy P, Mitra S, Lefebvre V. Sox5 and Sox6 are needed to develop and maintain source, columnar, and hypertrophic chondrocytes in the cartilage growth plate. J Cell Biol 2004; 164: 747-758. 38. Budinger TF. Nuclear magnetic resonance (NMR) in vivo studies: known thresholds for health effects. J Comput Assist Tomogr 1981; 5: 800-811. 39. Kerr JD. MRI safety: everyone's job. Radiol Manage 2001; 23: 36-39. 40. Mevissen M, Stamm A, Buntenkotter S, Zwingelberg R, Wahnschaffe U, Loscher W. Effects of magnetic fields on mammary tumor development induced by 7,12-dimethylbenz(a)anthracene in rats. Bioelectromagnetics 1993; 14: 131-143. 41. Rannug A, Ekstrom T, Mild KH, Holmberg B, Gimenez-Conti I, Slaga TJ. A study on skin tumour formation in mice with 50 Hz magnetic field exposure. Carcinogenesis 1993; 14: 573-578. 42. Hintenlang DE. Synergistic effects of ionizing radiation and 60 Hz magnetic fields. Bioelectromagnetics 1993; 14: 545-551. 43. Tofani S, Anglesio L, Ossola P, d'Amore G. Spectral analysis of magnetic fields from domestic appliances and corresponding induced current densities in an anatomically based model of the human head. Bioelectromagnetics 1995; 16: 356-364. 44. Cain CD, Thomas DL, Adey WR. 60 Hz magnetic field acts as co-promoter in focus formation of C3H/10T1/2 cells. Carcinogenesis 1993; 14: 955-960. 45. Cossarizza A, Monti D, Bersani F, Cantini M, Cadossi R, Sacchi A, et al. Extremely low frequency pulsed electromagnetic fields increase cell proliferation in lymphocytes from young and aged subjects. Biochem Biophys Res Commun 1989; 160: 692-698. 46. Cohly HH, Abraham GE, 3rd, Ndebele K, Jenkins JJ, Thompson J, Angel MF. Effects of static electromagnetic fields on characteristics of MG-63 osteoblasts grown in culture. Biomed Sci Instrum 2003; 39: 454-459. 47. Conti P, Gigante GE, Cifone MG, Alesse E, Ianni G, Reale M, et al. Reduced mitogenic stimulation of human lymphocytes by extremely low frequency electromagnetic fields. FEBS Lett 1983; 162: 156-160. 48. Hirai T, Nakamichi N, Yoneda Y. Activator protein-1 complex expressed by magnetism in cultured rat hippocampal neurons. Biochem Biophys Res Commun 2002; 292: 200-207. 49. Hiraoka M, Miyakoshi J, Li YP, Shung B, Takebe H, Abe M. Induction of c-fos gene expression by exposure to a static magnetic field in HeLaS3 cells. Cancer Res 1992; 52: 6522-6524. 50. Phillips JL, Haggren W, Thomas WJ, Ishida-Jones T, Adey WR. Magnetic field-induced changes in specific gene transcription. Biochim Biophys Acta 1992; 1132: 140-144. 51. Gandhi OP. Electromagnetic fields: human safety issues. Annu Rev Biomed Eng 2002; 4: 211-234. 52. Springer JE. Apoptotic cell death following traumatic injury to the central nervous system. J Biochem Mol Biol 2002; 35: 94-105. 53. Mehlen P, Thibert C. Dependence receptors: between life and death. Cell Mol Life Sci 2004; 61: 1854-1866. 54. Ding WX, Yin XM. Dissection of the multiple mechanisms of TNF-alpha-induced apoptosis in liver injury. J Cell Mol Med 2004; 8: 445-454. 55. Bredesen DE. Apoptosis: overview and signal transduction pathways. J Neurotrauma 2000; 17: 801-810. 56. Matiba B, Mariani SM, Krammer PH. The CD95 system and the death of a lymphocyte. Semin Immunol 1997; 9: 59-68. 57. Cho SG, Choi EJ. Apoptotic signaling pathways: caspases and stress-activated protein kinases. J Biochem Mol Biol 2002; 35: 24-27. 58. Allen RT, Cluck MW, Agrawal DK. Mechanisms controlling cellular suicide: role of Bcl-2 and caspases. Cell Mol Life Sci 1998; 54: 427-445. 59. Thorburn A. Death receptor-induced cell killing. Cell Signal 2004; 16: 139-144. 60. Porter AG, Urbano AG. Does apoptosis-inducing factor (AIF) have both life and death functions in cells? Bioessays 2006; 28: 834-843. 61. Kim R, Emi M, Tanabe K. Caspase-dependent and -independent cell death pathways after DNA damage (Review). Oncol Rep 2005; 14: 595-599. 62. Chowdhury I, Tharakan B, Bhat GK. Current concepts in apoptosis: The physiological suicide program revisited. Cell Mol Biol Lett 2006; 11: 506-525. 63. Lane DP, Crawford LV. T antigen is bound to a host protein in SV40-transformed cells. Nature 1979; 278: 261-263. 64. Linzer DI, Maltzman W, Levine AJ. The SV40 A gene product is required for the production of a 54,000 MW cellular tumor antigen. Virology 1979; 98: 308-318. 65. Levine AJ. The p53 protein and its interactions with the oncogene products of the small DNA tumor viruses. Virology 1990; 177: 419-426. 66. Nakamura Y. Isolation of p53-target genes and their functional analysis. Cancer Sci 2004; 95: 7-11. 67. Lane DP. Cancer. p53, guardian of the genome. Nature 1992; 358: 15-16. 68. Child ES, Mann DJ. The intricacies of p21 phosphorylation: protein/protein interactions, subcellular localization and stability. Cell Cycle 2006; 5: 1313-1319. 69. Coqueret O. New roles for p21 and p27 cell-cycle inhibitors: a function for each cell compartment? Trends Cell Biol 2003; 13: 65-70. 70. Lee MH, Yang HY. Negative regulators of cyclin-dependent kinases and their roles in cancers. Cell Mol Life Sci 2001; 58: 1907-1922. 71. Niculescu AB, 3rd, Chen X, Smeets M, Hengst L, Prives C, Reed SI. Effects of p21(Cip1/Waf1) at both the G1/S and the G2/M cell cycle transitions: pRb is a critical determinant in blocking DNA replication and in preventing endoreduplication. Mol Cell Biol 1998; 18: 629-643. 72. Waga S, Hannon GJ, Beach D, Stillman B. The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA. Nature 1994; 369: 574-578. 73. Dotto GP. p21(WAF1/Cip1): more than a break to the cell cycle? Biochim Biophys Acta 2000; 1471: M43-56. 74. Perkins ND. Not just a CDK inhibitor: regulation of transcription by p21(WAF1/CIP1/SDI1). Cell Cycle 2002; 1: 39-41. 75. Suzuki A, Kawano H, Hayashida M, Hayasaki Y, Tsutomi Y, Akahane K. Procaspase 3/p21 complex formation to resist fas-mediated cell death is initiated as a result of the phosphorylation of p21 by protein kinase A. Cell Death Differ 2000; 7: 721-728. 76. Muro Y, Yamada T, Himeno M, Sugimoto K. cDNA cloning of a novel autoantigen targeted by a minor subset of anti-centromere antibodies. Clin Exp Immunol 1998; 111: 372-376. 77. Hershko DD, Shapira M. Prognostic role of p27Kip1 deregulation in colorectal cancer. Cancer 2006; 107: 668-675. 78. Lloyd RV, Erickson LA, Jin L, Kulig E, Qian X, Cheville JC, et al. p27kip1: a multifunctional cyclin-dependent kinase inhibitor with prognostic significance in human cancers. Am J Pathol 1999; 154: 313-323. 79. Polyak K, Kato JY, Solomon MJ, Sherr CJ, Massague J, Roberts JM, et al. p27Kip1, a cyclin-Cdk inhibitor, links transforming growth factor-beta and contact inhibition to cell cycle arrest. Genes Dev 1994; 8: 9-22. 80. Kato JY, Matsuoka M, Polyak K, Massague J, Sherr CJ. Cyclic AMP-induced G1 phase arrest mediated by an inhibitor (p27Kip1) of cyclin-dependent kinase 4 activation. Cell 1994; 79: 487-496. 81. Firpo EJ, Koff A, Solomon MJ, Roberts JM. Inactivation of a Cdk2 inhibitor during interleukin 2-induced proliferation of human T lymphocytes. Mol Cell Biol 1994; 14: 4889-4901. 82. Kroemer G. The proto-oncogene Bcl-2 and its role in regulating apoptosis. Nat Med 1997; 3: 614-620. 83. Gupta S, Knowlton AA. HSP60, Bax, apoptosis and the heart. J Cell Mol Med 2005; 9: 51-58. 84. Jurgensmeier JM, Xie Z, Deveraux Q, Ellerby L, Bredesen D, Reed JC. Bax directly induces release of cytochrome c from isolated mitochondria. Proc Natl Acad Sci U S A 1998; 95: 4997-5002. 85. Ghatan S, Larner S, Kinoshita Y, Hetman M, Patel L, Xia Z, et al. p38 MAP kinase mediates bax translocation in nitric oxide-induced apoptosis in neurons. J Cell Biol 2000; 150: 335-347. 86. Courtney MJ, Enkvist MO, Akerman KE. The calcium response to the excitotoxin kainate is amplified by subsequent reduction of extracellular sodium. Neuroscience 1995; 68: 1051-1057. 87. Birkeland JA, Sejersted OM, Taraldsen T, Sjaastad I. EC-coupling in normal and failing hearts. Scand Cardiovasc J 2005; 39: 13-23. 88. Camello C, Lomax R, Petersen OH, Tepikin AV. Calcium leak from intracellular stores--the enigma of calcium signalling. Cell Calcium 2002; 32: 355-361. 89. Verkhratsky A. Endoplasmic reticulum calcium signaling in nerve cells. Biol Res 2004; 37: 693-699. 90. Berridge MJ, Lipp P, Bootman MD. The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol 2000; 1: 11-21. 91. Hajnoczky G, Csordas G, Das S, Garcia-Perez C, Saotome M, Sinha Roy S, et al. Mitochondrial calcium signalling and cell death: approaches for assessing the role of mitochondrial Ca2+ uptake in apoptosis. Cell Calcium 2006; 40: 553-560. 92. Korzh-Sleptsova IL, Lindstrom E, Mild KH, Berglund A, Lundgren E. Low frequency MFs increased inositol 1,4,5-trisphosphate levels in the Jurkat cell line. FEBS Lett 1995; 359: 151-154. 93. Lindstrom E, Lindstrom P, Berglund A, Mild KH, Lundgren E. Intracellular calcium oscillations induced in a T-cell line by a weak 50 Hz magnetic field. J Cell Physiol 1993; 156: 395-398. 94. Yamamoto Y, Ohsaki Y, Goto T, Nakasima A, Iijima T. Effects of static magnetic fields on bone formation in rat osteoblast cultures. J Dent Res 2003; 82: 962-966. 95. Yuge L, Okubo A, Miyashita T, Kumagai T, Nikawa T, Takeda S, et al. Physical stress by magnetic force accelerates differentiation of human osteoblasts. Biochem Biophys Res Commun 2003; 311: 32-38. 96. Binnig G, Quate CF, Gerber C. Atomic force microscope. Physical Review Letters 1986; 56: 930-933. 97. Gaboriaud F, Dufrene YF. Atomic force microscopy of microbial cells: application to nanomechanical properties, surface forces and molecular recognition forces. Colloids Surf B Biointerfaces 2007; 54: 10-19. 98. Gadegaard N. Atomic force microscopy in biology: technology and techniques. Biotech Histochem 2006; 81: 87-97. 99. Cai K, Bossert J, Jandt KD. Does the nanometre scale topography of titanium influence protein adsorption and cell proliferation? Colloids Surf B Biointerfaces 2006; 49: 136-144. 100. Frederix PL, Akiyama T, Staufer U, Gerber C, Fotiadis D, Muller DJ, et al. Atomic force bio-analytics. Curr Opin Chem Biol 2003; 7: 641-647. 101. Jena BP. Cell secretion machinery: studies using the AFM. Ultramicroscopy 2006; 106: 663-669. 102. Koitschev A, Fink S, Rexhausen U, Loffler K, Horber JK, Zenner HP, et al. [Atomic force microscope (AFM). A nanomanipulator for biophysical studies of stereocilia of the cochlear hair cells]. Hno 2002; 50: 464-469. 103. Ohnesorge FM, Horber JK, Haberle W, Czerny CP, Smith DP, Binnig G. AFM review study on pox viruses and living cells. Biophys J 1997; 73: 2183-2194. 104. Lin SM, Liauh CT, Wang WR, Ho SH. Analytical solutions of the first three frequency shifts of AFM non-uniform probe subjected to the Lennard-Jones force. Ultramicroscopy 2006; 106: 508-515. 105. Giessibl FJ. Theory for an electrostatic imaging mechanism allowing atomic resolution of ionic crystals by atomic force microscopy. Physical Review. B. Condensed Matter. 1992; 45: 13815-13818. 106. Colton RJ, Baselt DR, Dufrene YF, Green JB, Lee GU. Scanning probe microscopy. Curr Opin Chem Biol 1997; 1: 370-377. 107. Hansma HG, Hoh JH. Biomolecular imaging with the atomic force microscope. Annu Rev Biophys Biomol Struct 1994; 23: 115-139. 108. Putman CA, van der Werf KO, de Grooth BG, van Hulst NF, Greve J. Viscoelasticity of living cells allows high resolution imaging by tapping mode atomic force microscopy. Biophys J 1994; 67: 1749-1753. 109. Pang D, Vidic B, Rodgers J, Berman BL, Dritschilo A. Atomic force microscope imaging of DNA and DNA repair proteins: applications in radiobiological research. Radiat Oncol Investig 1997; 5: 163-169. 110. Kueng A, Kranz C, Lugstein A, Bertagnolli E, Mizaikoff B. Nanoelectrodes integrated in atomic force microscopy cantilevers for imaging of in situ enzyme activity. Methods Mol Biol 2005; 300: 403-415. 111. Johnson DJ, Miles NJ, Hilal N. Quantification of particle-bubble interactions using atomic force microscopy: A review. Adv Colloid Interface Sci 2006; 127: 67-81. 112. Ahlbom A, Day N, Feychting M, Roman E, Skinner J, Dockerty J, et al. A pooled analysis of magnetic fields and childhood leukaemia. Br J Cancer 2000; 83: 692-698. 113. Bobacz K, Graninger WB, Amoyo L, Smolen JS. Effect of pulsed electromagnetic fields on proteoglycan biosynthesis of articular cartilage is age dependent. Ann Rheum Dis 2006; 65: 949-951. 114. De Mattei M, Pasello M, Pellati A, Stabellini G, Massari L, Gemmati D, et al. Effects of electromagnetic fields on proteoglycan metabolism of bovine articular cartilage explants. Connect Tissue Res 2003; 44: 154-159. 115. De Mattei M, Pellati A, Pasello M, Ongaro A, Setti S, Massari L, et al. Effects of physical stimulation with electromagnetic field and insulin growth factor-I treatment on proteoglycan synthesis of bovine articular cartilage. Osteoarthritis Cartilage 2004; 12: 793-800. 116. Nakahara T, Yaguchi H, Yoshida M, Miyakoshi J. Effects of exposure of CHO-K1 cells to a 10-T static magnetic field. Radiology 2002; 224: 817-822. 117. Spinelli JJ, Band PR, Svirchev LM, Gallagher RP. Mortality and cancer incidence in aluminum reduction plant workers. J Occup Med 1991; 33: 1150-1155. 118. Barregard L, Jarvholm B, Ungethum E. Cancer among workers exposed to strong static magnetic fields. Lancet 1985; 2: 892. 119. Evans JA, Savitz DA, Kanal E, Gillen J. Infertility and pregnancy outcome among magnetic resonance imaging workers. J Occup Med 1993; 35: 1191-1195. 120. Mur JM, Moulin JJ, Meyer-Bisch C, Massin N, Coulon JP, Loulergue J. Mortality of aluminium reduction plant workers in France. Int J Epidemiol 1987; 16: 257-264. 121. Preston-Martin S, Navidi W, Thomas D, Lee PJ, Bowman J, Pogoda J. Los Angeles study of residential magnetic fields and childhood brain tumors. Am J Epidemiol 1996; 143: 105-119. 122. Sunk IG, Trattnig S, Graninger WB, Amoyo L, Tuerk B, Steiner CW, et al. Impairment of chondrocyte biosynthetic activity by exposure to 3-tesla high-field magnetic resonance imaging is temporary. Arthritis Res Ther 2006; 8: R106. 123. Hardingham GE, Bading H. Calcium as a versatile second messenger in the control of gene expression. Microsc Res Tech 1999; 46: 348-355. 124. Sionov RV, Haupt Y. The cellular response to p53: the decision between life and death. Oncogene 1999; 18: 6145-6157. 125. Fukatsu H. 3T MR for clinical use: update. Magn Reson Med Sci 2003; 2: 37-45. 126. Moser E, Trattnig S. 3.0 Tesla MR systems. Invest Radiol 2003; 38: 375-376. 127. Rimon G, Bazenet CE, Philpott KL, Rubin LL. Increased surface phosphatidylserine is an early marker of neuronal apoptosis. J Neurosci Res 1997; 48: 563-570. 128. Grynkiewicz G, Poenie M, Tsien RY. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem 1985; 260: 3440-3450. 129. Kheifets L, Shimkhada R. Childhood leukemia and EMF: review of the epidemiologic evidence. Bioelectromagnetics 2005; Suppl 7: S51-59. 130. Zwirska-Korczala K, Jochem J, Adamczyk-Sowa M, Sowa P, Polaniak R, Birkner E, et al. Effect of extremely low frequency of electromagnetic fields on cell proliferation, antioxidative enzyme activities and lipid peroxidation in 3T3-L1 preadipocytes - an in vitro study. J Physiol Pharmacol 2005; 56 Suppl 6: 101-108. 131. Miyakoshi J. Effects of static magnetic fields at the cellular level. Prog Biophys Mol Biol 2005; 87: 213-223. 132. Onodera H, Jin Z, Chida S, Suzuki Y, Tago H, Itoyama Y. Effects of 10-T static magnetic field on human peripheral blood immune cells. Radiat Res 2003; 159: 775-779. 133. Kim HJ, Chang IT, Heo SJ, Koak JY, Kim SK, Jang JH. Effect of magnetic field on the fibronectin adsorption, cell attachment and proliferation on titanium surface. Clin Oral Implants Res 2005; 16: 557-562. 134. Jajte J, Grzegorczyk J, Zmyslony M, Rajkowska E. Effect of 7 mT static magnetic field and iron ions on rat lymphocytes: apoptosis, necrosis and free radical processes. Bioelectrochemistry 2002; 57: 107-111. 135. Qiu LH, Tang XN, Zhong M, Wang ZY. [Effect of static magnetic field on proliferation and cell cycle of osteoblast cell.]. Shanghai Kou Qiang Yi Xue 2004; 13: 469-470. 136. Boya P, Cohen I, Zamzami N, Vieira HL, Kroemer G. Endoplasmic reticulum stress-induced cell death requires mitochondrial membrane permeabilization. Cell Death Differ 2002; 9: 465-467. 137. Breckenridge DG, Germain M, Mathai JP, Nguyen M, Shore GC. Regulation of apoptosis by endoplasmic reticulum pathways. Oncogene 2003; 22: 8608-8618. 138. McConkey DJ, Orrenius S. The role of calcium in the regulation of apoptosis. Biochem Biophys Res Commun 1997; 239: 357-366. 139. Liu S, Bishop WR, Liu M. Differential effects of cell cycle regulatory protein p21(WAF1/Cip1) on apoptosis and sensitivity to cancer chemotherapy. Drug Resist Updat 2003; 6: 183-195. 140. Yao K, Wang KJ, Sun ZH, Tan J, Xu W, Zhu LJ, et al. Low power microwave radiation inhibits the proliferation of rabbit lens epithelial cells by upregulating P27Kip1 expression. Mol Vis 2004; 10: 138-143. 141. Lange S, Viergutz T, Simko M. Modifications in cell cycle kinetics and in expression of G1 phase-regulating proteins in human amniotic cells after exposure to electromagnetic fields and ionizing radiation. Cell Prolif 2004; 37: 337-349. 142. Kim R, Emi M, Tanabe K. Role of mitochondria as the gardens of cell death. Cancer Chemother Pharmacol 2006; 57: 545-553. 143. Pavlov EV, Priault M, Pietkiewicz D, Cheng EH, Antonsson B, Manon S, et al. A novel, high conductance channel of mitochondria linked to apoptosis in mammalian cells and Bax expression in yeast. J Cell Biol 2001; 155: 725-731. 144. Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 1993; 74: 609-619. 145. Strniskova M, Barancik M, Ravingerova T. Mitogen-activated protein kinases and their role in regulation of cellular processes. Gen Physiol Biophys 2002; 21: 231-255. 146. Chu CT, Levinthal DJ, Kulich SM, Chalovich EM, DeFranco DB. Oxidative neuronal injury. The dark side of ERK1/2. Eur J Biochem 2004; 271: 2060-2066. 147. Shapiro F, Koide S, Glimcher MJ. Cell origin and differentiation in the repair of full-thickness defects of articular cartilage. J Bone Joint Surg Am 1993; 75: 532-553. 148. Drissi H, Zuscik M, Rosier R, O'Keefe R. Transcriptional regulation of chondrocyte maturation: potential involvement of transcription factors in OA pathogenesis. Mol Aspects Med 2005; 26: 169-179. 149. Goldring MB, Tsuchimochi K, Ijiri K. The control of chondrogenesis. J Cell Biochem 2006; 97: 33-44. 150. Lin Z, Willers C, Xu J, Zheng MH. The chondrocyte: biology and clinical application. Tissue Eng 2006; 12: 1971-1984. 151. Dudhia J. Aggrecan, aging and assembly in articular cartilage. Cell Mol Life Sci 2005; 62: 2241-2256. 152. Tyyni A, Karlsson J. Biological treatment of joint cartilage damage. Scand J Med Sci Sports 2000; 10: 249-265. 153. Stoltz JF, Netter P, Huselstein C, de Isla N, Wei Yang J, Muller S. [Chondrocyte mecanobiology. Application in cartilage tissue engineering]. Bull Acad Natl Med 2005; 189: 1803-1814; discussion 1814-1806. 154. Buckwalter JA, Mankin HJ. Articular cartilage: degeneration and osteoarthritis, repair, regeneration, and transplantation. Instr Course Lect 1998; 47: 487-504. 155. Buckwalter JA, Mankin HJ. Articular cartilage: tissue design and chondrocyte-matrix interactions. Instr Course Lect 1998; 47: 477-486. 156. Lohmander LS, Lark MW, Sandy JD. [Mechanisms of degradation of argecanes in osteoarthritic cartilage]. Rev Prat 1996; 46: S11-S14. 157. Lohmander LS, Neame PJ, Sandy JD. The structure of aggrecan fragments in human synovial fluid. Evidence that aggrecanase mediates cartilage degradation in inflammatory joint disease, joint injury, and osteoarthritis. Arthritis Rheum 1993; 36: 1214-1222. 158. Mitani H, Takahashi I, Onodera K, Bae JW, Sato T, Takahashi N, et al. Comparison of age-dependent expression of aggrecan and ADAMTSs in mandibular condylar cartilage, tibial growth plate, and articular cartilage in rats. Histochem Cell Biol 2006. 159. Sandy JD, Flannery CR, Neame PJ, Lohmander LS. The structure of aggrecan fragments in human synovial fluid. Evidence for the involvement in osteoarthritis of a novel proteinase which cleaves the Glu 373-Ala 374 bond of the interglobular domain. J Clin Invest 1992; 89: 1512-1516. 160. Buckwalter JA. Articular cartilage injuries. Clin Orthop Relat Res 2002: 21-37. 161. Forriol F, Shapiro F. Bone development: interaction of molecular components and biophysical forces. Clin Orthop Relat Res 2005: 14-33. 162. Kim HT, Lo MY, Pillarisetty R. Chondrocyte apoptosis following intraarticular fracture in humans. Osteoarthritis Cartilage 2002; 10: 747-749. 163. Loening AM, James IE, Levenston ME, Badger AM, Frank EH, Kurz B, et al. Injurious mechanical compression of bovine articular cartilage induces chondrocyte apoptosis. Arch Biochem Biophys 2000; 381: 205-212. 164. Loeser RF. Integrins and cell signaling in chondrocytes. Biorheology 2002; 39: 119-124. 165. Hynes RO. Integrins: versatility, modulation, and signaling in cell adhesion. Cell 1992; 69: 11-25. 166. Kurtis MS, Schmidt TA, Bugbee WD, Loeser RF, Sah RL. Integrin-mediated adhesion of human articular chondrocytes to cartilage. Arthritis Rheum 2003; 48: 110-118. 167. Buckwalter JA, Mankin HJ, Grodzinsky AJ. Articular cartilage and osteoarthritis. Instr Course Lect 2005; 54: 465-480. 168. Eyre DR, Wu JJ, Fernandes RJ, Pietka TA, Weis MA. Recent developments in cartilage research: matrix biology of the collagen II/IX/XI heterofibril network. Biochem Soc Trans 2002; 30: 893-899. 169. Poole AR, Kojima T, Yasuda T, Mwale F, Kobayashi M, Laverty S. Composition and structure of articular cartilage: a template for tissue repair. Clin Orthop Relat Res 2001: S26-33. 170. Schmal H, Mehlhorn AT, Fehrenbach M, Muller CA, Finkenzeller G, Sudkamp NP. Regulative mechanisms of chondrocyte adhesion. Tissue Eng 2006; 12: 741-750. 171. van der Kraan PM, Buma P, van Kuppevelt T, van den Berg WB. Interaction of chondrocytes, extracellular matrix and growth factors: relevance for articular cartilage tissue engineering. Osteoarthritis Cartilage 2002; 10: 631-637. 172. Solchaga LA, Goldberg VM, Caplan AI. Cartilage regeneration using principles of tissue engineering. Clin Orthop Relat Res 2001: S161-170. 173. Martin JA, Buckwalter JA. Aging, articular cartilage chondrocyte senescence and osteoarthritis. Biogerontology 2002; 3: 257-264. 174. Darling EM, Zauscher S, Guilak F. Viscoelastic properties of zonal articular chondrocytes measured by atomic force microscopy. Osteoarthritis Cartilage 2006. 175. Ganguli M, Babu JV, Maiti S. Complex formation between cationically modified gold nanoparticles and DNA: an atomic force microscopic study. Langmuir 2004; 20: 5165-5170. 176. Lesniewska E, Milhiet PE, Giocondi MC, Le Grimellec C. Atomic force microscope imaging of cells and membranes. Methods Cell Biol 2002; 68: 51-65. 177. Scott CC, Luttge A, Athanasiou KA. Development and validation of vertical scanning interferometry as a novel method for acquiring chondrocyte geometry. J Biomed Mater Res A 2005; 72: 83-90. 178. Wu Y, Cai J, Cheng L, Xu Y, Lin Z, Wang C, et al. Atomic force microscope tracking observation of Chinese hamster ovary cell mitosis. Micron 2006; 37: 139-145. 179. Stolz M, Raiteri R, Daniels AU, VanLandingham MR, Baschong W, Aebi U. Dynamic elastic modulus of porcine articular cartilage determined at two different levels of tissue organization by indentation-type atomic force microscopy. Biophys J 2004; 86: 3269-3283. 180. Kempson GE. Age-related changes in the tensile properties of human articular cartilage: a comparative study between the femoral head of the hip joint and the talus of the ankle joint. Biochim Biophys Acta 1991; 1075: 223-230. 181. Buckwalter JA, Martin J, Mankin HJ. Synovial joint degeneration and the syndrome of osteoarthritis. Instr Course Lect 2000; 49: 481-489. 182. Koepp H, Eger W, Muehleman C, Valdellon A, Buckwalter JA, Kuettner KE, et al. Prevalence of articular cartilage degeneration in the ankle and knee joints of human organ donors. J Orthop Sci 1999; 4: 407-412. 183. Verzijl N, DeGroot J, Ben ZC, Brau-Benjamin O, Maroudas A, Bank RA, et al. Crosslinking by advanced glycation end products increases the stiffness of the collagen network in human articular cartilage: a possible mechanism through which age is a risk factor for osteoarthritis. Arthritis Rheum 2002; 46: 114-123. 184. Bolton MC, Dudhia J, Bayliss MT. Age-related changes in the synthesis of link protein and aggrecan in human articular cartilage: implications for aggregate stability. Biochem J 1999; 337 ( Pt 1): 77-82. 185. Dozin B, Malpeli M, Camardella L, Cancedda R, Pietrangelo A. Response of young, aged and osteoarthritic human articular chondrocytes to inflammatory cytokines: molecular and cellular aspects. Matrix Biol 2002; 21: 449-459. 186. Messai H, Duchossoy Y, Khatib AM, Panasyuk A, Mitrovic DR. Articular chondrocytes from aging rats respond poorly to insulin-like growth factor-1: an altered signaling pathway. Mech Ageing Dev 2000; 115: 21-37. 187. Rosen F, McCabe G, Quach J, Solan J, Terkeltaub R, Seegmiller JE, et al. Differential effects of aging on human chondrocyte responses to transforming growth factor beta: increased pyrophosphate production and decreased cell proliferation. Arthritis Rheum 1997; 40: 1275-1281. 188. Matzke R, Jacobson K, Radmacher M. Direct, high-resolution measurement of furrow stiffening during division of adherent cells. Nat Cell Biol 2001; 3: 607-610. 189. Radmacher M. Measuring the elastic properties of living cells by the atomic force microscope. Methods Cell Biol 2002; 68: 67-90. 190. Schneider SW, Matzke R, Radmacher M, Oberleithner H. Shape and volume of living aldosterone-sensitive cells imaged with the atomic force microscope. Methods Mol Biol 2004; 242: 255-279. 191. Brakebusch C, Fassler R. beta 1 integrin function in vivo: adhesion, migration and more. Cancer Metastasis Rev 2005; 24: 403-411. 192. Lapadula G, Iannone F, Zuccaro C, Grattagliano V, Covelli M, Patella V, et al. Chondrocyte phenotyping in human osteoarthritis. Clin Rheumatol 1998; 17: 99-104. 193. DeGroot J, Verzijl N, Bank RA, Lafeber FP, Bijlsma JW, TeKoppele JM. Age-related decrease in proteoglycan synthesis of human articular chondrocytes: the role of nonenzymatic glycation. Arthritis Rheum 1999; 42: 1003-1009. 194. Mayne R. Cartilage collagens. What is their function, and are they involved in articular disease? Arthritis Rheum 1989; 32: 241-246. 195. Kuo CK, Li WJ, Mauck RL, Tuan RS. Cartilage tissue engineering: its potential and uses. Curr Opin Rheumatol 2006; 18: 64-73. 196. Benya PD, Shaffer JD. Dedifferentiated chondrocytes reexpress the differentiated collagen phenotype when cultured in agarose gels. Cell 1982; 30: 215-224. 197. Schnabel M, Marlovits S, Eckhoff G, Fichtel I, Gotzen L, Vecsei V, et al. Dedifferentiation-associated changes in morphology and gene expression in primary human articular chondrocytes in cell culture. Osteoarthritis Cartilage 2002; 10: 62-70. 198. Andrei G. Three-dimensional culture models for human viral diseases and antiviral drug development. Antiviral Res 2006; 71: 96-107. 199. Liu X, Ma PX. Polymeric scaffolds for bone tissue engineering. Ann Biomed Eng 2004; 32: 477-486. 200. Martin I. [Engineering 3D cartilage grafts]. Schweiz Rundsch Med Prax 2006; 95: 841-844. 201. Martin I, Miot S, Barbero A, Jakob M, Wendt D. Osteochondral tissue engineering. J Biomech 2007; 40: 750-765. 202. Chen MH, Broom ND. Concerning the ultrastructural origin of large-scale swelling in articular cartilage. J Anat 1999; 194 ( Pt 3): 445-461. 203. Clark KA, McElhinny AS, Beckerle MC, Gregorio CC. Striated muscle cytoarchitecture: an intricate web of form and function. Annu Rev Cell Dev Biol 2002; 18: 637-706. 204. Towler MC, Kaufman SJ, Brodsky FM. Membrane traffic in skeletal muscle. Traffic 2004; 5: 129-139. 205. Magnusson P, Larsson L, Englund G, Larsson B, Strang P, Selin-Sjogren L. Differences of bone alkaline phosphatase isoforms in metastatic bone disease and discrepant effects of clodronate on different skeletal sites indicated by the location of pain. Clin Chem 1998; 44: 1621-1628. 206. Karsenty G, Park RW. Regulation of type I collagen genes expression. Int Rev Immunol 1995; 12: 177-185. 207. Lefebvre V, Garofalo S, de Crombrugghe B. Type X collagen gene expression in mouse chondrocytes immortalized by a temperature-sensitive simian virus 40 large tumor antigen. J Cell Biol 1995; 128: 239-245. 208. Ahsan T, Sah RL. Biomechanics of integrative cartilage repair. Osteoarthritis Cartilage 1999; 7: 29-40. 209. Wilson W, Driessen NJ, van Donkelaar CC, Ito K. Prediction of collagen orientation in articular cartilage by a collagen remodeling algorithm. Osteoarthritis Cartilage 2006; 14: 1196-1202. | en |
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