Age-related degeneration of articular cartilage in the pathogenesis of osteoarthritis: Molecular markers of senescent chondrocytes

Histology and Histopathology

Volumn 30, Issue 1, 2015, Pages 1-12

  Musumeci, Giuseppe ^a   Szychlinska, Marta Anna ^a   Mobasheri, Ali ^b,c,d  

^a UNIVERSITY OF CATANIA   (Italy)

^b UNIVERSITY OF SURREY   (United Kingdom)

^c UNIVERSITY OF NOTTINGHAM   (United Kingdom)

^d KING ABDULAZIZ UNIVERSITY   (Saudi Arabia)

Author keywords

Aging; Cartilage; Chondrocyte; Lubricin; Osteoarthritis; Senescence; Senescence markers

Indexed keywords

BIOLOGICAL MARKER;

ARTICULAR CARTILAGE; CARTILAGE CELL; CELL AGING; HUMAN; METABOLISM; OSTEOARTHRITIS; OXIDATIVE STRESS; PATHOLOGY;

BIOLOGICAL MARKERS; CARTILAGE, ARTICULAR; CELL AGING; CHONDROCYTES; HUMANS; OSTEOARTHRITIS; OXIDATIVE STRESS;

EID: 84916624406     PISSN: 02133911     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (108)

1. Acosta J.C., O'Loghlen A., Banito A., Guijarro M.V., Augert A., Raguz S., Fumagalli M., Da Costa M., Brown C., Popov N., Takatsu Y., Melamed J., d'Adda di Fagagna F., Bernard D., Hernando E. and Gil J. (2008). Chemokine signaling via the CXCR2 receptor reinforces senescence. Cell 133, 1006-1018.
2. Adams C.S. and Horton W.E. (1998). Chondrocyte apoptosis increases with age in the articular cartilage of adult animals. Jr. Anat. Rec. 250, 418-425.
3. Adams P.D. (2007). Remodeling of chromatin structure in senescent cells and its potential impact on tumor suppression and aging. Gene 397, 84-93.
4. Aigner T., Kurz B., Fukui N. and Sandell L. (2002). Roles of chondrocytes in the pathogenesis of osteoarthritis. Curr. Opin. Rheumatol. 14, 578-584.
5. Aigner T., Kim H.A. and Roach H.I. (2004a). Apoptosis in osteoarthritis. Rheum. Dis. Clin. North. Am. 30, 639-653.
6. Aigner T., Rose J., Martin J. and Buckwalter J. (2004b). Aging theories of primary osteoarthritis: from epidemiology to molecular biology. Rejuvenation. Res. 7, 134-145.
7. Aigner T., Soder S., Gebhard P.M., McAlinden A. and Haag J. (2007). Mechanisms of disease: role of chondrocytes in the pathogenesis of osteoarthritis-structure, chaos and senescence. Nat. Clin. Pract. Rheumatol. 3, 391-399.
8. Akagi M. (2010). Chondrocyte senescence and osteoarthritis : role of oxidized LDL-induced oxidative stress. Acta Medica Kinki University 35, 1-13.
9. Artandi S.E. and DePinho R.A. (2000). A critical role for telomeres in suppressing and facilitating carcinogenesis. Curr. Opin. Genet. Dev. 10, 39-46.
10. Aurich M., Poole A.R., Reiner A., Mollenhauer C., Margulis A., Kuettner K.E. and Cole A.A. (2002). Matrix homeostasis in aging normal human ankle cartilage. Arthritis. Rheum. 46, 2903-2910.
11. Beauséjour C.M., Krtolica A., Galimi F., Narita M., Lowe S.W., Yaswen P. and Campisi J. (2003). Reversal of human cellular senescence: roles of the p53 and p16 pathways. EMBO J. 22, 4212-4222.
12. Ben-Porath I. and Weinberg R.A. (2005). The signals and pathways activating cellular senescence. Int. J. Biochem. Cell. Biol. 37, 961-976.
13. Bobacz K., Gruber R., Soleiman A., Erlacher L., Smolen J.S. and Graninger W.B. (2003). Expression of bone morphogenetic protein 6 in healthy and osteoarthritic human articular chondrocytes and stimulation of matrix synthesis in vitro. Arthritis Rheum. 48, 2501-2508.
14. Bodnar A.G., Ouellette M., Frolkis M., Holt S.E., Chiu C.P., Morin G.B., Harley C.B., Shay J.W., Lichtsteiner S. and Wright W.E. (1998). Extension of life-span by introduction of telomerase into normal human cells. Science 279, 349-352.
15. Bolton M.C., Dudhia J. and Bayliss M.T. (1999). Age-related changes in the synthesis of link protein and aggrecan in human articular cartilage: implications for aggregate stability. Biochem. J. 33, 777-782.
16. Brunet A. and Berger S.L.J. (2014). Epigenetics of aging and agingrelated disease. Gerontol. A. Biol. Sci. Med. Sci. 69, S17-20.
17. Bryan T.M. and Cech T.R. (1999). Telomerase and the maintenance of chromosome ends. Curr. Opin. Cell. Biol. 11, 318-324.
18. Buckwalter J.A. and Rosenberg L.C. (1988). Electron microscopic studies of cartilage proteoglycans, Elec. Microsc. Rev. 1, 87-112.
19. Buckwalter J.A. and Mankin H.J. (1998a). Articular cartilage: degeneration and osteoarthritis, repair, regeneration, and transplantation. Instr. Course Lect. 47, 487-504.
20. Buckwalter J.A. and Mankin H.J. (1998b). Articular cartilage: tissue design and chondrocyte-matrix interactions. Instr. Course Lect. 47, 477-486.
21. Buckwalter J.A., Choi H., Tang L., Rosenberg L. and Ungar R. (1986). The effect of link protein concentration of proteoglycan aggregation. Trans. 32nd Meeting Ortho. Res. Soc. pp 11-98.
22. Buckwalter J.A., Martin J.A. and Mankin H.J. (2000). Synovial joint degeneration and the syndrome of osteoarthritis. Ciba. Geigy. Instr. Course Lect. 49, 481-489.
23. Caltabiano R., Leonardi R., Musumeci G., Bartoloni G., Rusu M.C., Almeida L.E. and Loreto C. (2013). Apoptosis in temporomandibular joint disc with internal derangement involves mitochondrialdependent pathways. An in vivo study. Acta Odontol. Scand. 71, 577-583.
24. Campisi J. (2005). Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 120, 513-522.
25. Campisi J. and d'Adda di Fagagna F. (2007). Cellular senescence: when bad things happen to good cells. Nat. Rev. Mol. Cell. Biol. 8, 729-740.
26. Cardile V., Musumeci G., Sicurezza E., Caggia S., Rusu M.C., Leonardi R. and Loreto C. (2013). Expression of TRAIL and its receptors DR5 and DcR2 in orthodontic tooth movement. Histol. Histopathol. 28, 933-940.
27. Cecil D.L., Johnson K., Rediske J., Lotz M., Schmidt A.M. and Terkeltaub R. (2005). Inflammation-induced chondrocyte hypertrophy is driven by receptor for advanced glycation end products. J. Immunol. 175, 8296-8302.
28. Chen J. and Goligorsky M.S. (2006). Premature senescence of endothelial cells: Methusaleh's dilemma. Am. J. Physiol. Heart. Circ. Physiol. 290, H1729-1739.
29. Cristofalo V.J., Lorenzini A., Allen R.G., Torres C. and Tresini M. (2004). Replicative senescence: a critical review. Mech. Ageing Dev. 125, 827-828.
30. Cukusic Kalajzic A., Vidacek N.S., Huzak M., Ivankovic M. and Rubelj I. (2014). Telomere Q-PNA-FISH--reliable results from stochastic signals. PLoS One 9, e92559.
31. Dai S.M., Shan Z.Z., Nakamura H., Masuko-Hongo K., Kato T., Nishioka K. and Yudoh K. (2006). Catabolic stress induces features of chondrocyte senescence through overexpression of caveolin 1: possible involvement of caveolin 1-induced downregulation of articular chondrocytes in the pathogenesis of osteoarthritis. Arthritis Rheum. 54, 818-831.
32. Davies C.M., Guilak F., Weinberg J.B. and Fermor B. (2008). Reactive nitrogen and oxygen species in interleukin-1-mediated DNA damage associated with osteoarthritis. Osteoarthritis. Cartilage 16, 624-630.
33. de Lange T. and Jacks T. (1999). For better or worse? Telomerase inhibition and cancer. Cell 98, 273-275.
34. DeGroot J., Verzijl N., Bank R.A., Lafeber F.P., Bijlsma J.W. and TeKoppele J.M. (1999). Age-related decrease in proteoglycan synthesis of human articular chondrocytes: the role of nonenzymatic glycation. Arthritis Rheum. 42, 1003-1009.
35. Del Carlo M. Jr and Loeser R.F. (2003). Increased oxidative stress with aging reduces chondrocyte survival: Correlation with intracellular glutathione levels. Arthritis Rheum. 48, 3419-3430.
36. Ding C., Cicuttini F., Scott F., Cooley H. and Jones G. (2005). Association between age and knee structural change: a cross sectional MRI based study. Ann. Rheum. Dis. 64, 549-555.
37. Doherty M. and Dieppe P. (1988). Clinical aspects of calcium pyrophosphate dihydrate crystal deposition. Rheum. Dis. Clin. North. Am. 14, 395-414.
38. Felson D.T., Anderson J.J., Naimark A., Kannel W. and Meenan R.F. (1989). The prevalence of chondrocalcinosis in the elderly and its association with knee osteoarthritis: the Framingham Study. J. Rheumatol. 16, 1241-1245.
39. Finkel T. and Holbrook N.J. (2000). Oxidants, oxidative stress and the biology of ageing. Nature 408, 239-247.
40. Galanti C., Musumeci G., Valentino J., Giunta S. and Castorina S. (2013). A role for apoptosis in temporomandibularjoint disc degeneration. A contemporary review. Ital. J. Anat. Embryol. 118, 151-158.
41. Goldring M.B. and Goldring S.R. (2007). Osteoarthritis. J. Cell. Physiol. 213, 626-634.
42. Greider C.W. (1998). Telomerase activity, cell proliferation, and cancer. Proc. Natl. Acad. Sci. USA 95, 90-92.
43. Hayflick L. (1984). Intracellular determinants of cell aging. Mech. Ageing Dev. 28, 177-185.
44. Herbig U. and Sedivy J.M. (2006). Regulation of growth arrest in senescence: telomere damage is not the end of the story. Mech. Ageing Dev. 127, 16-24.
45. Hollander A.P., Pidoux I., Reiner A., Rorabeck C., Bourne R. and Poole A.R. (1995). Damage to type II collagen in aging and osteoarthritis starts at the articular surface, originates around chondrocytes, and extends into the cartilage with progressive degeneration. J. Clin. Invest. 96, 2859-2869.
46. Horton W.E. Jr, Feng L. and Adams C. (1998). Chondrocyte apoptosis in development, aging and disease. Matrix Biol. 17, 107-115.
47. Hudelmaier M., Glaser C., Hohe J., Englmeier K.H., Reiser M., Putz R. and Eckstein F. (2001). Age-related changes in the morphology and deformational behavior of knee joint cartilage. Arthritis Rheum. 44, 2556-2561.
48. Itahana K., Campisi J. and Dimri G.P. (2004). Mechanisms of cellular senescence in human and mouse cells. Biogerontology 5, 1-10.
49. Itahana K., Campisi J. and Dimri G.P. (2007). Methods to detect biomarkers of cellular senescence: the senescence-associated betagalactosidase assay. Methods Mol. Biol. 371, 21-31.
50. Iwamoto M., Ohta Y., Larmour C. and Enomoto-Iwamoto M. (2013). Toward regeneration of articular cartilage. Birth Defects Res. C. Embryo Today 99, 192-202.
51. James A.M., Thomas B., Anneliese H. and Joseph A. (2004). Buckwalter Post-traumatic osteoarthritis: the role of accelerated chondrocyte senescence. Biorheology 41, 479-491.
52. Kamata H. and Hirata H. (1999). Redox regulation of cellular signalling. Cell. Signal. 11, 1-14.
53. Kuhn K., D'Lima D.D., Hashimoto S. and Lotz M. (2004). Cell death in cartilage. Osteoarthritis Cartilage 12, 1-16.
54. Kupiec M. (2014). Biology of telomeres: lessons from budding yeast. FEMS Microbiol. Rev. 38, 144-171.
55. Kurz D.J., Decary S., Hong Y. and Erusalimsky J.D. (2000). Senescence-associated (beta)-galactosidase reflects an increase in lysosomal mass during replicative ageing of human endothelial cells. J. Cell. Sci. 113, 3613-3622.
56. Kurz B., Lemke A.K., Fay J., Pufe T., Grodzinsky A.J. and Schunke M. (2005). Pathomechanisms of cartilage destruction by mechanical injury. Ann. Anat. 187, 473-485.
57. Lee A.S., Ellman M.B., Yan D., Kroin J.S., Cole B.J., van Wijnen A.J. and Im H.J. (2013). A current review of molecular mechanisms regarding osteoarthritis and pain. Gene 527, 440-447.
58. Leonardi R., Loreto C., Barbato E., Caltabiano R., Lombardo C., Musumeci G. and Lo Muzio L. (2008). MMP-13 (collagenase 3) localization in human temporomandibular joint discs with internal derangement. Acta Histochem. 110, 314-318.
59. Leonardi R., Rusu M.C., Loreto F., Loreto C. and Musumeci G. (2011). Immunolocalization and expression of lubricin in the bilaminar zone of the human temporomandibular joint disc. Acta Histochem. 114, 1-5.
60. Leonardi R., Loreto C., Talic N., Caltabiano R. and Musumeci G. (2012a). Immunolocalization of lubricin in the rat periodontal ligament during experimental tooth movement. Acta Histochem. 114, 700-704.
61. Leonardi R., Musumeci G., Sicurezza E. and Loreto C. (2012b). Lubricin in human temporomandibular joint disc: an immunohistochemical study. Arch. Oral. Biol. 57, 614-619.
62. Loeser R.F. (2004). Aging cartilage and osteoarthritis--what's the link? Jr. Sci. Aging Knowledge Environ. 2004, 31.
63. Loeser R.F., Yammani R.R., Carlson C.S., Chen H., Cole A., Im H.J., Bursch L.S. and Yan S.D. (2005). Articular chondrocytes express the receptor for advanced glycation end products: Potential role in osteoarthritis. Arthritis Rheum. 52, 2376-2385.
64. Loreto C., Barbagli G., Djinovic R., Vespasiani G., Carnazza M.L., Miano R., Musumeci G. and Sansalone S. (2011a). Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its death receptor (DR5) in Peyronie's disease. A biomolecular study of apoptosis activation. J. Sex Med. 8, 109-15.
65. Loreto C., Musumeci G., Castorina A., Loreto C. and Martinez G. (2011b). Degenerative disc disease of herniated intervertebral discs is associated with extracellular matrix remodeling, vimentin-positive cells and cell death. Ann. Anat. 193, 156-162.
66. Loreto C., Leonardi R., Musumeci G., Pannone G. and Castorina S. (2013). An ex vivo study on immunohistochemical localization of MMP-7 and MMP-9 in temporomandibular joint discs with internal derangement. Eur. J. Histochem. 57, e12.
67. Mankin H.J. (1963). Localization of tritiated thymidine in articular cartilage of rabbits. J. Bone Joint. Surg. 45, 529-540.
68. Martin J.A. and Buckwalter J.A. (2000). The role of chondrocyte-matrix interactions in maintaining and repairing articular cartilage, Biorheology 37, 129-140.
69. Martin J.A. and Buckwalter J.A. (2001a). Roles of articular cartilage aging and chondrocyte senescence in the pathogenesis of osteoarthritis. Iowa. Orthop. J. 21, 1-7.
70. Martin J.A. and Buckwalter J.A. (2001b). Telomere erosion and senescence in human articular cartilage chondrocytes. J. Gerontol. A. Biol. Sci. Med. Sci. 56, B172-179.
71. Martin J.A. and Buckwalter J.A. (2003). The role of chondrocyte senescence in the pathogenesis of osteoarthritis and in limiting cartilage repair. J. Bone. Joint. Surg. Am. 85, 106-110.
72. Martin J.A., Ellerbroek S.M. and Buckwalter J.A. (1997). Age-related decline in chondrocyte response to insulin-like growth factor-I: the role of growth factor binding proteins. J. Orthop. Res. 15, 491-498.
73. Martin J.A., Brown T., Heiner A. and Buckwalter J.A. (2004a). Posttraumatic osteoarthritis: the role of accelerated chondrocyte senescence. Biorheology 41, 479-491.
74. Martin J.A., Klingelhutz A.J., Moussavi-Harami F. and Buckwalter J.A. (2004b). Effects of oxidative damage and telomerase activity on human articular cartilage chondrocyte senescence. J. Gerontol. A. Biol. Sci. Med. Sci. 59, 324-337.
75. Matthews C., Gorenne I., Scott S., Figg N., Kirkpatrick P., Ritchie A., Goddard M. and Bennett M. (2006). Vascular smooth muscle cells undergo telomere-based senescence in human atherosclerosis: effects of telomerase and oxidative stress. Circ. Res. 99, 156-164.
76. Muller M. (2009). Cellular senescence: molecular mechanisms, in vivo significance, and redox considerations. Antioxid. Redox. Signal. 11, 59-98.
77. Musumeci G., Loreto C., Cardile V., Carnazza M.L. and Martinez G. (2010). Immunohistochemical expression of retinoblastoma and phospho-retinoblastoma protein in sheep lung exposed to fluoroedenite fibers. Anat. Sci. Int. 85, 74-78.
78. Musumeci G., Loreto C., Carnazza M.L. and Martinez G. (2011a). Characterization of apoptosis in articular cartilage derived from the knee joints of patients with osteoarthritis. Knee Surg. Sports Traumatol. Arthrosc. 19, 307-313.
79. Musumeci G., Loreto C., Carnazza M.L., Strehin I. and Elisseeff J. (2011b). OA cartilage derived chondrocytes encapsulated in poly(ethylene glycol) diacrylate (PEGDA) for the evaluation of cartilage restoration and apoptosis in an in vitro model. Histol. Histopathol. 26, 1265-1278.
80. Musumeci G., Cardile V., Fenga C., Caggia S. and Loreto C. (2011c). Mineral fibre toxicity: expression of retinoblastoma (Rb) and phospho-retinoblastoma (pRb) protein in alveolar epithelial and mesothelial cell lines exposed to fluoro-edenite fibres. Cell. Biol. Toxicol. 27, 217-225.
81. Musumeci G., Leonardi R, Carnazza M.L., Cardile V., Pichler K., Weinberg A.M. and Loreto C. (2013a). Aquaporin 1 (AQP1) expression in experimentally induced osteoarthritic knee menisci: an in vivo and in vitro study. Tissue Cell 45, 145-152.
82. Musumeci G., Loreto C., Castorina S., Imbesi R., Leonardi R. and Castrogiovanni P. (2013b). New perspectives in the treatment of cartilage damage. Poly(ethylene glycol) diacrylate (PEGDA) scaffold. A review. Ital. J. Anat. Embryol. 118, 204-210.
83. Musumeci G., Loreto C., Castorina S., Imbesi R., Leonardi R. and Castrogiovanni P. (2013c). Current Concepts in the Treatment of Cartilage Damage. A Review. Ital. J. Anat. Embryol. 118, 189-203.
84. Musumeci G., Trovato F.M., Pichler K., Weinberg A.M., Loreto C. and Castrogiovanni P. (2013d). Extra-virgin olive oil diet and mild physical activity prevent cartilage degeneration in an osteoarthritis model. An "in vivo" and "in vitro" study on lubricin expression. J. Nutr. Biochem. 24, 2064-2075.
85. Musumeci G., Loreto C., Leonardi R., Castorina S., Giunta S., Carnazza M.L., Trovato F.M., Pichler K. and Weinberg A.M. (2013e). The effects of physical activity on apoptosis and lubricin expression in articular cartilage in rats with glucocorticoid-induced osteoporosis. J. Bone Miner. Metab. 31, 274-284.
86. Musumeci G., Loreto C., Carnazza M.L., Cardile V. and Leonardi R. (2013f). Acute injury affects lubricin expression in knee menisci: an immunohistochemical study. Ann. Anat. 195, 151-158.
87. Musumeci G., Castrogiovanni P., Leonardi R., Trovato F.M., Szychlinska M.A., Di Giunta A., Loreto C. and Castorina S. (2014a). New perspectives for articular cartilage repair treatment through tissue engineering: A contemporary review. World J. Orthop. 5, 80-88.
88. Musumeci G., Castrogiovanni P., Mazzone V., Szychlinska M.A., Castorina S. and Loreto C. (2014b). Histochemistry as a unique approach for investigating normal and osteoarthritic cartilage. Eur. J. Histochem. 58, 107-111.
89. Musumeci G., Loreto C., Imbesi R., Trovato F.M., Di Giunta A., Lombardo C., Castorina S. and Castrogiovanni P. (2014c). Advantages of exercise in rehabilitation, treatment and prevention of altered morphological features in knee osteoarthritis. A narrative review. Histol. Histopathol. 29, 707-719.
90. Musumeci G., Castrogiovanni P., Trovato F.M., Imbesi R., Giunta S., Szychlinska M.A., Loreto C., Castorina S., Mobasheri A. (2014d). Mild physical activity ameliorates cartilage degeneration in a rat model of aging: A study on lubricin expression. Scand. J. Med. Sci. Sports (in press).
91. Philipot D., Guérit D., Platano D., Chuchana P., Olivotto E., Espinoza F., Dorandeu A., Pers Y.M., Piette J., Borzi R.M., Jorgensen C., Noel D. and Brondello J.M. (2014). p16INK4a and its regulator miR-24 link senescence and chondrocyte terminal differentiation-associated matrix remodelling in osteoarthritis. Arthritis Res. Ther. 16, R58.
92. Price J.S., Waters J.G., Darrah C., Pennington C., Edwards D.R., Donell S.T. and Clark I.M. (2002). The role of chondrocyte senescence in osteoarthritis. Aging Cell 1, 57-65.
93. Puzzo D., Loreto C., Giunta S., Musumeci G., Frasca G., Podda M.V., Arancio O. and Palmeri A. (2014). Effect of phosphodiesterase-5 inhibition on apoptosis and beta amyloid load in aged mice. Neurobiol. Aging 35, 520-531.
94. Rosen F., McCabe G., Quach J., Solan J., Terkeltaub R., Seegmiller J.E. and Lotz M. (1997). Differential effects of aging on human chondrocyte responses to transforming growth factor beta: increased pyrophosphate production and decreased cell proliferation. Arthritis Rheum. 40, 1275-1281.
95. Rosenthal A.K., Derfus B.A. and Henry L.A. (1997). Transglutaminase activity in aging articular chondrocytes and articular cartilage vesicles. Arthritis Rheum. 40, 966-970.
96. Scharstuhl A., van Beuningen H.M., Vitters E.L., van der Kraan P.M. and van den Berg W.B. (2002). Loss of transforming growth factor counteraction on interleukin 1 mediated effects in cartilage of old mice. Ann. Rheum. Dis. 61, 1095-1098.
97. Squires G.R., Okouneff A., Ionescu M. and Pool A.R. (2003). The pathobiology of focal lesion development in aging human articular cartilage and molecular matrix changes characteristic of osteoarthritis. Arthritis Rheum. 48, 1261-1270.
98. Takahashi A., Ohtani N., Yamakoshi K., Iida S., Tahara H., Nakayama K., Nakayama K.I., Ide T., Saya H. and Hara E. (2006). Mitogenic signalling and the p16INK4a-Rb pathway cooperate to enforce irreversible cellular senescence. Nat. Cell Biol. 8, 1291-1297.
99. Tomiyama T., Fukuda K., Yamazaki K., Hashimoto K., Ueda H., Mori S. and Hamanishi C. (2007). Cyclic compression loaded on cartilage explants enhances the production of reactive oxygen species. J. Rheumatol. 34, 556-562.
100. Verzijl N., DeGroot J., Ben Z.C., Brau-Benjamin O., Maroudas A., Bank R.A., Mizrahi J., Schalkwijk C.G., Thorpe S.R., Baynes J.W., Bijlsma J.W., Lafeber F.P. and TeKoppele J.M. (2002). 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. 46, 114-123.
101. Vignon E., Arlot M., Patricot L.M. and Vignon G. (1976). The cell density of human femoral head cartilage. Clin. Orthop. 121, 303-308.
102. Wajapeyee N., Serra R.W., Zhu X., Mahalingam M. and Green M.R. (2008). Oncogenic BRAF induces senescence and apoptosis through pathways mediated by the secreted protein IGFBP7. Cell 132, 363-374.
103. Wolf A.D. and Pfleger B. (2003). Burden of major musculoskeletal conditions. Policy and practice. Special theme-bone and joint decade 2000-2010. Bull. World Health Organ. 81, 646-656.
104. Yammani R.R., Carlson C.S., Bresnick A.R. and Loeser R.F. (2006). Increase in production of matrix metalloproteinase 13 by human articular chondrocytes due to stimulation with S100A4: Role of the receptor for advanced glycation end products. Arthritis Rheum. 54, 2901-2911.
105. Yudoh K., Nguyenv T., Nakamura H., Hongo-Masuko K., Kato T. and Nishioka K. (2005). Potential involvement of oxidative stress in cartilage senescence and development of osteoarthritis: oxidative stress induces chondrocyte telomere instability and downregulation of chondrocyte function. Arthritis Res. Ther. 7, R380-391.
106. Zhang H., Pan K.H. and Cohen S.N. (2003). Senescence-specific gene expression fingerprints reveal cell-type-dependent physical clustering of up-regulated chromosomal loci. Proc. Natl. Acad. Sci. USA 100, 3251-3256.
107. Zhang R. and Adams P.D. (2007). Heterochromatin and its relationship to cell senescence and cancer therapy. Cell Cycle 6, 784-789.
108. Zhou X. and Xing D. (2012). Assays for human telomerase activity: progress and prospects. Chem. Soc. Rev. 41, 4643-4656.