Anabolic and catabolic mRNA levels of the intervertebral disc vary with the magnitude and frequency of in vivo dynamic compression.
The goal of this study was to characterize the anabolic and catabolic mRNA response of the disc to dynamic loading to determine if variations in the magnitude and/or frequency of loading could elicit different cellular responses. Sixty-eight Wistar rats were instrumented with an Ilizarov-type device spanning caudal disc 8-9. Seventy-two hours after surgery, animals were anesthetized and loaded at either 1 or 0.2 MPa at a frequency of 1, 0.2 or 0.01 Hz for 2 h (6 groups). The surgical control (Sham) animals underwent anesthesia with no loading. Loaded (c8-9) and internal-control discs (c6-7 and c10-11) were dissected and annulus and nucleus tissue were separately analyzed by real-time RT-PCR for levels of anabolic (collagen-1A1, collagen-2A1, aggrecan) and catabolic (MMP-3, MMP-13, ADAMTs-4) mRNA. In the nucleus, a frequency-dependent response was seen at 1 MPa with anabolic genes stimulated at 0.01 Hz and catabolic genes at 1 Hz. In the annulus all frequencies resulted in significant up-regulation of catabolic mRNA at 1 MPa loading. In general loading at 0.2 MPa or 0.2 Hz had little effect on gene expression. The results suggest that gene expression of the annulus appears to be more dependent on the magnitude of applied stress, while the nucleus is both magnitude- and frequency-dependent.
Department of Mechanical Engineering, University of Vermont, 231B Votey Building, 33 Colchester Avenue, Burlington 05405-0156, USA.
Jeffery J
JJ
Maclean
Cynthia R
CR
Lee
Mauro
M
Alini
James C
JC
Iatridis
D051722:ADAM Proteins; D000071121:ADAMTS4 Protein; D053674:Aggrecans; D000818:Animals; D003094:Collagen / Q000235:genetics; D017364:Collagenases / Q000235:genetics; D019245:Compressive Strength / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000235:genetics; D015870:Gene Expression / Q000502:physiology*; D007403:Intervertebral Disc / Q000502:physiology*; D037181:Lectins, C-Type; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D008666:Metalloendopeptidases / Q000235:genetics; D023421:Models, Animal; D011348:Procollagen N-Endopeptidase; D011509:Proteoglycans / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012337:RNA, Ribosomal, 18S / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016474:Weight-Bearing / Q000502:physiology
C508321:Acan protein, rat; D053674:Aggrecans; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D011509:Proteoglycans; D012333:RNA, Messenger; D012337:RNA, Ribosomal, 18S; D003094:Collagen; D051722:ADAM Proteins; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; D008666:Metalloendopeptidases; C507083:Mmp13 protein, rat; D011348:Procollagen N-Endopeptidase; D019278:Matrix Metalloproteinase 3; D000071121:ADAMTS4 Protein