title: Loss of extracellular matrix from articular cartilage is mediated by the synovium and ligament after anterior cruciate ligament injury.
abstract: OBJECTIVE
  Post-traumatic osteoarthritis (PTOA) occurs after anterior cruciate ligament (ACL) injury. PTOA may be initiated by early expression of proteolytic enzymes capable of causing degradation of the articular cartilage at time of injury. This study investigated the production of three of these key proteases in multiple joint tissues after ACL injury and subsequent markers of cartilage turnover.
  
  
  METHODS
  ACL transection was performed in adolescent minipigs. Collagenase (MMP-1 and MMP-13) and aggrecanase (ADAMTS-4) gene expression changes were quantified in the articular cartilage, synovium, injured ligament, and the provisional scaffold at days 1, 5, 9, and 14 post-injury. Markers of collagen degradation (C2C), synthesis (CPII) and aggrecan synthesis (CS 846) were quantified in the serum and synovial fluid. Histologic assessment of the cartilage integrity (OARSI scoring) was also performed.
  
  
  RESULTS
  MMP-1 gene expression was upregulated in the articular cartilage, synovium and ligament after ACL injury. MMP-13 expression was suppressed in the articular cartilage, but upregulated 100-fold in the synovium and ligament. ADAMTS-4 was upregulated in the synovium and ligament but not in the articular cartilage. The concentration of collagen degradation fragments (C2C) in the synovial joint fluid nearly doubled in the first five days after injury.
  
  
  CONCLUSIONS
  We conclude that upregulation of genes coding for proteins capable of degrading cartilage ECM is seen within the first few days after ACL injury, and this response is seen not only in chondrocytes, but also in cells in the synovium, ligament and provisional scaffold.
authors.affiliation: Department of Orthopaedic Surgery, Boston Children's Hospital, Boston, MA, USA. Electronic address: Carla.Haslauer@childrens.harvard.edu.
authors.forename: C M
authors.initials: CM
authors.lastname: Haslauer
authors.forename: K A
authors.initials: KA
authors.lastname: Elsaid
authors.forename: B C
authors.initials: BC
authors.lastname: Fleming
authors.forename: B L
authors.initials: BL
authors.lastname: Proffen
authors.forename: V M
authors.initials: VM
authors.lastname: Johnson
authors.forename: M M
authors.initials: MM
authors.lastname: Murray
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism; D000071121:ADAMTS4 Protein; D053674:Aggrecans / Q000378:metabolism; D000818:Animals; D016118:Anterior Cruciate Ligament / Q000201:enzymology*; D000070598:Anterior Cruciate Ligament Injuries; D002358:Cartilage, Articular / Q000378:metabolism*; D024043:Collagen Type II / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005786:Gene Expression Regulation; D007719:Knee Joint / Q000201:enzymology* / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D011348:Procollagen N-Endopeptidase / Q000235:genetics / Q000378:metabolism; D013552:Swine; D013556:Swine, Miniature; D013582:Synovial Fluid / Q000378:metabolism; D013583:Synovial Membrane / Q000201:enzymology*; D015854:Up-Regulation
chemical_list: D053674:Aggrecans; D024043:Collagen Type II; D051722:ADAM Proteins; D053509:Matrix Metalloproteinase 13; D011348:Procollagen N-Endopeptidase; D020781:Matrix Metalloproteinase 1; D000071121:ADAMTS4 Protein
keywords: ACL; Aggrecanase; Cartilage; Joint tissues; Metalloproteinases
references.citation: Arthritis Rheum. 2010 Aug;62(8):2382-91
references.pmid: 20506144
references.citation: J Clin Invest. 1997 Apr 1;99(7):1534-45
references.pmid: 9119997
references.citation: Arthritis Rheum. 2001 Jan;44(1):120-7
references.pmid: 11212149
references.citation: Orthop Clin North Am. 2003 Jan;34(1):149-67
references.pmid: 12735207
references.citation: Am J Sports Med. 2010 Dec;38(12):2528-34
references.pmid: 20855556
references.citation: Vet J. 2011 Dec;190(3):390-5
references.pmid: 21216637
references.citation: J Rheumatol. 2004 Jan;31(1):110-9
references.pmid: 14705229
references.citation: Clin Orthop Relat Res. 2006 Jan;442:39-44
references.pmid: 16394737
references.citation: J Orthop Res. 2007 Jan;25(1):81-91
references.pmid: 17031861
references.citation: Arthritis Rheum. 2002 Aug;46(8):2087-94
references.pmid: 12209513
references.citation: Osteoarthritis Cartilage. 2010 May;18(5):662-7
references.pmid: 20188685
references.citation: Am J Vet Res. 2010 Jul;71(7):741-9
references.pmid: 20594075
references.citation: J Bone Joint Surg Am. 2001 Jun;83(6):826-38
references.pmid: 11407790
references.citation: Arch Orthop Trauma Surg. 1997;116(1-2):19-21
references.pmid: 9006759
references.citation: J Immunol Methods. 2004 Nov;294(1-2):145-53
references.pmid: 15637808
references.citation: Biochim Biophys Acta. 2001 May 3;1526(2):147-58
references.pmid: 11325536
references.citation: Am J Sports Med. 2012 Feb;40(2):276-85
references.pmid: 21952715
references.citation: Am J Sports Med. 2010 Feb;38(2):348-56
references.pmid: 19966107
references.citation: J Orthop Res. 2010 Jul;28(7):900-6
references.pmid: 20108346
references.citation: Osteoarthritis Cartilage. 2006 Jan;14(1):13-29
references.pmid: 16242352
references.citation: Osteoarthritis Cartilage. 2002 Aug;10(8):662-9
references.pmid: 12479389
references.citation: J Clin Invest. 1994 Jul;94(1):25-33
references.pmid: 7518830
references.citation: Connect Tissue Res. 2009;50(5):315-22
references.pmid: 19863390
references.citation: Arthritis Rheum. 2004 Feb;50(2):543-52
references.pmid: 14872497
references.citation: Nat Protoc. 2008;3(6):1101-8
references.pmid: 18546601
references.citation: J Orthop Res. 2006 Apr;24(4):820-30
references.pmid: 16555312
references.citation: Arthritis Rheum. 1999 Mar;42(3):534-44
references.pmid: 10088777
references.citation: Ann Rheum Dis. 2005 May;64(5):694-8
references.pmid: 15834054
references.citation: Osteoarthritis Cartilage. 2007 Jul;15(7):819-23
references.pmid: 17344068
references.citation: Arthritis Rheum. 2012 Jul;64(7):2278-88
references.pmid: 22307759
references.citation: J Clin Invest. 1998 Dec 15;102(12):2115-25
references.pmid: 9854047
references.citation: Osteoarthritis Cartilage. 2012 Apr;20(4):271-8
references.pmid: 22273632
references.citation: Osteoarthritis Cartilage. 2012 Nov;20(11):1302-8
references.pmid: 22874525
references.citation: Knee Surg Sports Traumatol Arthrosc. 2013 Apr;21(4):942-9
references.pmid: 22898911
references.citation: J Biol Chem. 2000 Oct 20;275(42):33027-37
references.pmid: 10882746
references.citation: Arthritis Rheum. 1999 May;42(5):861-70
references.pmid: 10323441
references.citation: J Orthop Res. 2011 Jun;29(6):802-9
references.pmid: 21520254
references.citation: Arthritis Res Ther. 2008;10(3):R63
references.pmid: 18513402
references.citation: J Bone Joint Surg Am. 2010 Sep 1;92(11):2039-49
references.pmid: 20810854
references.citation: Microsc Microanal. 2011 Oct;17(5):779-87
references.pmid: 21910939
references.citation: J Thromb Haemost. 2012 Dec;10(12):2494-502
references.pmid: 23067060
references.citation: Front Biosci. 2006 Jan 01;11:529-43
references.pmid: 16146751
references.citation: Am J Vet Res. 2010 Aug;71(8):946-52
references.pmid: 20673095
references.citation: Arthritis Res Ther. 2010;12(6):R229
references.pmid: 21194441
references.citation: Am J Sports Med. 2007 Oct;35(10):1756-69
references.pmid: 17761605
references.citation: Arthritis Rheum. 2003 Nov;48(11):3130-9
references.pmid: 14613275