Cellular and epigenetic features of a young healthy and a young osteoarthritic cartilage compared with aged control and OA cartilage.
Osteoarthritis (OA) is generally a disease of the elderly population, but can occur in young patients in exceptional cases. This study compares the cellular and epigenetic features of primary old-age OA with those of secondary OA in a 23-year-old patient with developmental dysplasia of the hip. In addition, control cartilage from a 14-year-old was compared with that from patients with a fracture of the neck of femur (#NOF) to establish to what extent the latter is a useful control for OA. Articular cartilage was obtained from discarded femoral heads after hip arthroplasty. MMP-3, MMP-9, MMP-13, and ADAMTS-4 were immunolocalized and the methylation status of specific promoter CpG sites was determined. Both primary and secondary OA were characterized by loss of aggrecan, formation of clones, and abnormal expression of the proteases that correlated with epigenetic DNA demethylation. The latter indicated that the abnormal expression of the cartilage-degrading proteases was not due to a short-term up-regulation, but a heritable, permanent alteration in gene expression. Comparing cell densities in young and old control cartilage estimated an age-related cell loss of approximately 1% per year. In aged #NOF cartilage, some superficial-zone chondrocytes expressed the proteases, but the majority of cells were immunonegative and their promoters were hypermethylated. The cellular and epigenetic features of the intermediate and deep zones of #NOF cartilage are thus similar to those of young healthy cartilage, justifying the use of #NOF cartilage as control cartilage for OA, providing the superficial zone is removed.
da Silva
Marco A
MA
Bone and Joint Research Group, University of Southampton, Southampton, United Kingdom.
Yamada
Norikazu
N
Clarke
Nicholas M P
NM
Roach
Helmtrud I
HI
D051722:ADAM Proteins / Q000378:metabolism; D000071121:ADAMTS4 Protein; D000293:Adolescent; D000368:Aged; D000369:Aged, 80 and over; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D019902:Chondrocytes / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005265:Femoral Neck Fractures / Q000378:metabolism; D005270:Femur Head / Q000473:pathology; D006618:Hip Dislocation, Congenital / Q000378:metabolism; D006801:Humans; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D011348:Procollagen N-Endopeptidase / Q000378:metabolism; D055815:Young Adult
D051722:ADAM Proteins; D053509:Matrix Metalloproteinase 13; D011348:Procollagen N-Endopeptidase; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9; D000071121:ADAMTS4 Protein; C000603918:ADAMTS4 protein, human