Characterization of pro-apoptotic and matrix-degradative gene expression following induction of osteoarthritis in mature and aged rabbits.
OBJECTIVE
The genetic and molecular changes leading to the distinctive alterations of aged cartilage and its propensity for developing osteoarthritis (OA) are unknown. We hypothesized that pro-apoptotic and matrix-degradative gene expression in a rabbit model of induced OA using mature and aged animals might elucidate this relationship.


METHODS
Groups of six mature and aged rabbits underwent anterior cruciate ligament transection (ACLT) and were sacrificed 4 weeks after surgery to create an Outerbridge grade II OA. RNA was extracted from the articular cartilage and menisci of the affected knee and was examined with regard to expression of the following genes: Caspase 8, Fas, Fas ligand (Fas-L), p53, aggrecanase, matrix metalloproteinase (MMP)-1, and MMP-3-MMP-13. A second cohort of mature and aged animals was sacrificed with no intervention to the joint and gene expression was assessed in a similar manner.


RESULTS
Fas and Caspase 8 showed significantly increased expression in the cartilage of mature animals with induced OA when compared to unoperated controls while induction of OA in aged rabbits did not significantly increase expression of any of the apoptosis genes. Among unoperated animals, the aged cohort showed significantly increased expression of MMP-1 and aggrecanase in cartilage when compared to mature animals. MMP-13 expression was upregulated in aged cartilage following induction of OA. Although ACLT animals showed gross thinning and irregularities within the meniscus, only the expression of Caspase 8 in the aged rabbits was significantly increased after induction of OA.


CONCLUSIONS
Aging of articular cartilage shares some qualities with the development of OA, as seen in the parallel increases in gene expression of Caspase 8 and Fas. Although this may imply a common mechanism of cartilage degeneration in aging and OA or even a spectrum of disease, both are complex processes requiring further study.
Robertson
C M
CM
Department of Orthopaedic Surgery, University of California San Diego, La Jolla, 92093-0630, USA.
Pennock
A T
AT
Harwood
F L
FL
Pomerleau
A C
AC
Allen
R T
RT
Amiel
D
D
D000375:Aging / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D002358:Cartilage, Articular / Q000503:physiopathology; D053181:Caspase 8; D020169:Caspases / Q000235:genetics; D004195:Disease Models, Animal; D010450:Endopeptidases / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics; D053222:Fas Ligand Protein; D015870:Gene Expression / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics; D006614:Hindlimb; D020782:Matrix Metalloproteinases / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics; D008592:Menisci, Tibial / Q000503:physiopathology; D010003:Osteoarthritis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D048069:Tumor Necrosis Factors / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; D016326:Extracellular Matrix Proteins; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D048069:Tumor Necrosis Factors; D010450:Endopeptidases; D053181:Caspase 8; D020169:Caspases; D020782:Matrix Metalloproteinases; C083641:aggrecanase