title: Transcriptome analysis of injured human meniscus reveals a distinct phenotype of meniscus degeneration with aging.
abstract: OBJECTIVE
  Meniscus tears are associated with a heightened risk of osteoarthritis. This study aimed to advance our understanding of the metabolic state of injured human meniscus at the time of arthroscopic partial meniscectomy through transcriptome-wide analysis of gene expression in relation to the patient's age and degree of cartilage chondrosis.
  
  
  METHODS
  The degree of chondrosis of knee cartilage was recorded at the time of meniscectomy in symptomatic patients without radiographic osteoarthritis. RNA preparations from resected menisci (n = 12) were subjected to transcriptome-wide microarray and QuantiGene Plex analyses. Variations in the relative changes in gene expression with age and chondrosis were analyzed, and integrated biologic processes were investigated computationally.
  
  
  RESULTS
  We identified a set of genes in torn menisci that were differentially expressed with age and chondrosis. There were 866 genes that were differentially regulated (≥1.5-fold difference and P < 0.05) with age and 49 with chondrosis. In older patients, genes associated with cartilage and skeletal development and extracellular matrix synthesis were repressed, while those involved in immune response, inflammation, cell cycle, and cellular proliferation were stimulated. With chondrosis, genes representing cell catabolism (cAMP catabolic process) and tissue and endothelial cell development were repressed, and those involved in T cell differentiation and apoptosis were elevated.
  
  
  CONCLUSIONS
  Differences in age-related gene expression suggest that in older adults, meniscal cells might dedifferentiate and initiate a proliferative phenotype. Conversely, meniscal cells in younger patients appear to respond to injury, but they maintain the differentiated phenotype. Definitive molecular signatures identified in damaged meniscus could be segregated largely with age and, to a lesser extent, with chondrosis.
authors: Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, MO 63017, USA.
authors: Muhammad Farooq
authors: MF
authors: Rai
authors: Debabrata
authors: D
authors: Patra
authors: Linda J
authors: LJ
authors: Sandell
authors: Robert H
authors: RH
authors: Brophy
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000375:Aging; D002357:Cartilage Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D054337:Cell Dedifferentiation / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007718:Knee Injuries / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D022125:Lacerations; D008592:Menisci, Tibial / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D040081:Protein Array Analysis / Q000379:methods*; D000070600:Tibial Meniscus Injuries
references: J Bone Joint Surg Br. 1948 Nov;30B(4):664-70
references: 18894618
references: Cell Mol Life Sci. 2002 Jan;59(1):45-53
references: 11846032
references: Iowa Orthop J. 2001;21:1-7
references: 11813939
references: Arthritis Rheum. 2006 Mar;54(3):795-801
references: 16508930
references: Nucleic Acids Symp Ser. 1991;(24):197-200
references: 1668687
references: Int J Obes (Lond). 2013 Sep;37(9):1238-46
references: 23318714
references: Ann Rheum Dis. 2005 Apr;64(4):556-63
references: 15374855
references: J Bone Joint Surg Am. 2012 Mar 7;94(5):385-93
references: 22362494
references: Arthritis Rheum. 2009 Mar;60(3):633-5
references: 19248081
references: J Bone Joint Surg Br. 1961 Nov;43-B:752-7
references: 14038135
references: Knee Surg Sports Traumatol Arthrosc. 2004 Jul;12(4):262-70
references: 14504718
references: Radiol Clin North Am. 2009 Jul;47(4):703-12
references: 19631077
references: Osteoarthritis Cartilage. 2012 Jan;20(1):49-59
references: 22062355
references: Osteoarthritis Cartilage. 2001 Jan;9(1):33-41
references: 11178945
references: Clin Orthop Relat Res. 1999 Oct;(367 Suppl):S281-92
references: 10546653
references: Arthritis Res Ther. 2008;10(4):R79
references: 18620607
references: J Bone Joint Surg Br. 2006 Dec;88(12):1549-56
references: 17159163
references: AJR Am J Roentgenol. 1991 Oct;157(4):799-806
references: 1892040
references: Arthroscopy. 2005 Nov;21(11):1366-9
references: 16325089
references: Rheumatology (Oxford). 2001 Jun;40(6):631-9
references: 11426019
references: Osteoarthritis Cartilage. 2011 Sep;19(9):1132-41
references: 21683797
references: Clin Orthop Relat Res. 2004 Oct;(427 Suppl):S27-36
references: 15480070
references: Osteoarthritis Cartilage. 1995 Dec;3(4):261-7
references: 8689461
references: Biotechniques. 2006 Apr;40(4):481-6
references: 16629395
references: Acta Orthop. 2012 Feb;83(1):59-64
references: 22206448
references: Am J Sports Med. 1986 Jul-Aug;14(4):270-5
references: 3755296
references: Arthritis Rheum. 2012 Mar;64(3):705-17
references: 21972019
references: J Bone Joint Surg Br. 1975 May;57(2):180-6
references: 1173585
references: Arch Biochem Biophys. 2010 Feb 15;494(2):138-44
references: 19944061
references: Arthritis Rheum. 2001 Jun;44(6):1237-47
references: 11407681
references: Osteoarthritis Cartilage. 2004 Nov;12(11):917-23
references: 15501408
references: J Appl Physiol (1985). 2003 Jul;95(1):308-13
references: 12665533
references: Crit Rev Eukaryot Gene Expr. 2011;21(2):131-42
references: 22077152
references: Arthritis Rheum. 2003 May;48(5):1261-70
references: 12746899
references: Nat Biotechnol. 2006 Sep;24(9):1115-22
references: 16964225
references: BMC Musculoskelet Disord. 2010 Jan 28;11:19
references: 20109188
references: Ann Rheum Dis. 2005 Dec;64(12):1721-6
references: 15843446
references: Arthritis Rheum. 2007 May;56(5):1529-36
references: 17469132
references: Arthritis Res Ther. 2010;12(2):R56
references: 20353559
references: J Rheumatol. 1994 Feb;21(2):307-13
references: 8182642
references: Osteoarthritis Cartilage. 2010 Mar;18(3):336-43
references: 19914195
references: Br J Sports Med. 2000 Aug;34(4):252-7
references: 10953895
references: Arthritis Rheum. 2003 Aug;48(8):2178-87
references: 12905471
references: Arthritis Rheum. 1998 Apr;41(4):687-93
references: 9550478
references: Am J Sports Med. 1991 Nov-Dec;19(6):632-7; discussion 637-8
references: 1781503
references: Am J Sports Med. 2007 Oct;35(10):1756-69
references: 17761605
references: Rheum Dis Clin North Am. 1993 Aug;19(3):545-68
references: 8210574
references: Arthritis Res Ther. 2009;11(3):227
references: 19519925
references: Toxicol Sci. 2012 Dec;130(2):257-68
references: 22903823
references: Rheumatology (Oxford). 2002 Aug;41(8):917-23
references: 12154209