title: Gene profiling of the rat medial collateral ligament during early healing using microarray analysis.
abstract: Ligament heals in a synchronized and complex series of events. The remodeling process may last months or years. Experimental evidence suggests the damaged ligament does not recover its normal functional properties. Specific mechanisms to prevent scar formation and to regenerate the original mechanical function remain elusive but likely involve regulation of creeping substitution. Creeping substitution creates a larger hypercellular, hypervascular, and disorganized granulation tissue mass that results in an inefficient and nonregenerative wound healing process for the ligament. Control of creeping substitution may limit the extent of this tissue compromise and reduce the time necessary for healing. The objective of this study is to better understand the mechanism behind scar formation by identifying the extracellular matrix factors and other unique genes of interest differentially expressed during rat ligament healing via microarray. For this study, rat medial collateral ligaments were either surgically transected or left intact. Ligaments were collected at day 3 or 7 postinjury and used for microarray, quantitative PCR, and/or immunohistochemistry. Results were compared with the normal intact ligament. We demonstrate that early ligament healing is characterized by the modulation of several inflammatory and extracellular matrix factors during the first week of injury. Specifically, a number of matrix metalloproteinases and collagens are differentially and significantly expressed during early ligament healing. Additionally, we demonstrate the modulation of three novel genes, periostin, collagen-triple helix repeat containing-1, and serine protease 35 in our ligament healing model. Together, control of granulation tissue creeping substitution and subsequent downstream scar formation is likely to involve these factors.
authors: Department of Orthopedics and Rehabilitation, University of Wisconsin, Madison, WI 53705, USA.
authors: Connie S
authors: CS
authors: Chamberlain
authors: Sabrina H
authors: SH
authors: Brounts
authors: David G
authors: DG
authors: Sterken
authors: Kevin I
authors: KI
authors: Rolnick
authors: Geoffrey S
authors: GS
authors: Baer
authors: Ray
authors: R
authors: Vanderby
references: J Cell Biol. 1986 Mar;102(3):703-10
references: 3456350
references: Am J Physiol Heart Circ Physiol. 2006 Jan;290(1):H323-30
references: 16143656
references: Mini Rev Med Chem. 2006 Nov;6(11):1243-8
references: 17100635
references: Physiol Rev. 2004 Jul;84(3):767-801
references: 15269336
references: Am J Hum Genet. 2000 Jun;66(6):1757-65
references: 10796876
references: Biol Reprod. 2006 Dec;75(6):823-35
references: 16870946
references: J Biol Chem. 1994 Nov 11;269(45):28193-9
references: 7961756
references: Biochem Biophys Res Commun. 2004 Nov 12;324(2):534-46
references: 15474460
references: J Appl Physiol (1985). 2009 Feb;106(2):506-12
references: 19036888
references: Invest Ophthalmol Vis Sci. 2007 Jul;48(7):3161-77
references: 17591886
references: Cancer Res. 2008 Dec 15;68(24):10324-32
references: 19074901
references: Bone. 2007 Oct;41(4):535-42
references: 17693149
references: Endocrinology. 2008 Oct;149(10):5070-7
references: 18566130
references: J Hand Surg Eur Vol. 2007 Oct;32(5):581-7
references: 17950228
references: J Clin Invest. 1991 Sep;88(3):904-10
references: 1832175
references: Wound Repair Regen. 2009 Mar-Apr;17(2):206-15
references: 19320889
references: J Biomech. 2004 Jun;37(6):865-77
references: 15111074
references: J Biol Chem. 2007 Apr 27;282(17):12791-5
references: 17331945
references: J Immunol. 2005 Jun 1;174(11):7250-6
references: 15905571
references: Methods. 2001 Dec;25(4):443-51
references: 11846613
references: J Biol Chem. 2000 Apr 7;275(14):10370-8
references: 10744725
references: J Invest Dermatol. 1992 Dec;99(6):870-2
references: 1469302
references: Int J Mol Med. 2000 Oct;6(4):391-407
references: 10998429
references: Mol Cell Biochem. 1997 Mar;168(1-2):1-12
references: 9062888
references: Biotechniques. 1997 Jun;22(6):1082-6
references: 9187757
references: J Clin Invest. 2007 Nov;117(11):3498-506
references: 17965778
references: Scand J Med Sci Sports. 2006 Feb;16(1):19-26
references: 16430677
references: Biosci Biotechnol Biochem. 2007 May;71(5):1154-61
references: 17485851
references: World J Gastroenterol. 2005 Oct 28;11(40):6312-21
references: 16419160
references: Invasion Metastasis. 1994-1995;14(1-6):269-75
references: 7657519
references: Respir Res. 2005 Dec 16;6:148
references: 16359550
references: Connect Tissue Res. 2009;50(5):315-22
references: 19863390
references: Ann Rheum Dis. 1999 Nov;58(11):691-7
references: 10531073
references: Circ Res. 2007 Mar 30;100(6):826-33
references: 17322174
references: Am J Respir Cell Mol Biol. 2001 May;24(5):537-44
references: 11350822
references: Brain Res. 2007 Nov 14;1180:140-54
references: 17919462
references: PLoS One. 2008 Jun 04;3(6):e2343
references: 18523579
references: Ann Surg. 1965 Feb;161:293-308
references: 14260029
references: J Clin Pathol. 2008 Apr;61(4):494-8
references: 17938160
references: Br J Sports Med. 2010 Dec;44(16):1160-5
references: 19443461
references: Trends Cardiovasc Med. 2007 Aug;17(6):202-5
references: 17662915
references: J Biomed Mater Res. 1998 Mar 5;39(3):462-8
references: 9468057
references: Nat Genet. 1995 Jan;9(1):31-6
references: 7704020
references: Am J Pathol. 1998 Jun;152(6):1489-99
references: 9626053
references: Dev Biol. 2008 Apr 15;316(2):200-13
references: 18313657
references: J Cell Biol. 1997 Jun 16;137(6):1445-57
references: 9182674
references: Cancer Res. 2006 May 15;66(10):5234-41
references: 16707448
references: Circ Res. 2005 Feb 4;96(2):261-8
references: 15618538
references: Joint Bone Spine. 2002 Mar;69(2):189-94
references: 12027311
references: Am J Med Genet. 1998 Oct 12;79(5):376-82
references: 9779805
references: Infect Immun. 2005 Jan;73(1):126-34
references: 15618147
references: J Orthop Res. 2001 Nov;19(6):1203-9
references: 11781025
references: J Biol Chem. 2003 Oct 31;278(44):43236-44
references: 12874293
references: Clin Exp Dermatol. 1999 Mar;24(2):122-6
references: 10233668
references: J Orthop Res. 2011 Oct;29(10):1604-12
references: 21469182
references: Cancer Res. 1997 May 15;57(10):2055-60
references: 9158005
references: J Orthop Res. 2006 Jan;24(1):71-9
references: 16419971
references: J Immunol. 2010 Apr 1;184(7):3955-63
references: 20181883
references: J Clin Invest. 1996 May 1;97(9):2011-9
references: 8621789
references: Anal Biochem. 2005 Oct 1;345(1):102-9
references: 16139233
references: Int Immunopharmacol. 2005 Mar;5(3):511-24
references: 15683848
references: J Orthop Res. 2004 May;22(3):520-5
references: 15099630
references: Biochimie. 2005 Mar-Apr;87(3-4):299-306
references: 15781316
references: J Cell Biochem. 2007 Jun 1;101(3):695-711
references: 17226767
references: J Immunol. 2002 Apr 1;168(7):3557-62
references: 11907119
references: J Orthop Res. 2002 Nov;20(6):1315-22
references: 12472246
references: Lab Invest. 1997 May;76(5):717-28
references: 9166290
references: Endocrinology. 1999 Sep;140(9):4351-8
references: 10465309
references: Circ Res. 2007 Aug 3;101(3):313-21
references: 17569887
references: J Neuroimmunol. 2001 Jun 1;116(2):213-9
references: 11438176
references: Am J Hum Genet. 2000 Nov;67(5):1083-94
references: 11007540
references: J Biol Chem. 2009 Jun 5;284(23):15676-84
references: 19342382
references: Am J Pathol. 2009 Aug;175(2):533-46
references: 19590036
references: J Bone Miner Res. 1999 Jul;14(7):1239-49
references: 10404027
references: Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):3942-6
references: 8632994
references: Z Kardiol. 1995;84 Suppl 4:137-44
references: 8585266