Analysis of lapine cartilage matrix after radiosynovectomy with holmium-166 ferric hydroxide macroaggregate.
OBJECTIVE
To study the short and long term effects of radiosynovectomy on articular cartilage in growing and mature rabbits.


METHODS
The articular cartilage of the distal femurs of rabbits was examined four days, two months, and one year after radiosynovectomy with holmium-166 ferric hydroxide macroaggregate ([(166)Ho]FHMA). Arthritic changes were evaluated from histological sections by conventional and polarised light microscopy, and glycosaminoglycan measurements using safranin O staining, digital densitometry, and uronic acid determination. Proteoglycan synthesis was studied by metabolic [(35)]sulphate labelling followed by autoradiography, and electrophoretic analysis of extracted proteoglycans. Northern analyses were performed to determine the mRNA levels of type II collagen, aggrecan, and Sox9 in cartilage samples.


RESULTS
Radiosynovectomy had no major effect on the histological appearance of articular cartilage in mature rabbits, whereas more fibrillation was seen in [(166)Ho]FHMA radiosynovectomised knee joints of growing rabbits two months after treatment, but not after one year. Radiosynovectomy did not cause changes in the glycosaminoglycan content of cartilage or in the synthesis or chemical structure of proteoglycans. No radiosynovectomy related changes were seen in the mRNA levels of type II collagen, whereas a transient down regulation of aggrecan and Sox9 mRNA levels was seen in young rabbits two months after [(166)Ho]FHMA radiosynovectomy.


CONCLUSIONS
[(166)Ho]FHMA radiosynovectomy caused no obvious chondrocyte damage or osteoarthritic changes in mature rabbits, but in growing rabbits some transient radiation induced effects were seen--for example, mild cartilage fibrillation and down regulation of cartilage-specific genes.
Mäkelä
O T
OT
Department of Clinical Veterinary Sciences, Faculty of Veterinary Medicine, PO Box 57, FIN-00014 University of Helsinki, Finland. olli.makela@helsinki.fi
Lammi
M J
MJ
Uusitalo
H
H
Hyttinen
M M
MM
Vuorio
E
E
Helminen
H J
HJ
Tulamo
R-M
RM
D000367:Age Factors; D053674:Aggrecans; D000818:Animals; D001168:Arthritis / Q000473:pathology / Q000532:radiotherapy*; D015152:Blotting, Northern / Q000379:methods; D002358:Cartilage, Articular / Q000254:growth & development / Q000473:pathology / Q000528:radiation effects*; D024043:Collagen Type II / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D016326:Extracellular Matrix Proteins; D005269:Femur; D005290:Ferric Compounds / Q000627:therapeutic use; D006025:Glycosaminoglycans / Q000032:analysis; D006609:High Mobility Group Proteins / Q000235:genetics; D006695:Holmium / Q000627:therapeutic use; D037181:Lectins, C-Type; D023421:Models, Animal; D011509:Proteoglycans / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D011868:Radioisotopes / Q000627:therapeutic use; D055758:SOX9 Transcription Factor; D018709:Statistics, Nonparametric; D013583:Synovial Membrane / Q000473:pathology / Q000528:radiation effects*; D014157:Transcription Factors / Q000235:genetics
D053674:Aggrecans; D024043:Collagen Type II; D016326:Extracellular Matrix Proteins; D005290:Ferric Compounds; D006025:Glycosaminoglycans; D006609:High Mobility Group Proteins; D037181:Lectins, C-Type; D011509:Proteoglycans; D012333:RNA, Messenger; D011868:Radioisotopes; D055758:SOX9 Transcription Factor; D014157:Transcription Factors; C000499:ferric oxide; D006695:Holmium