Articular chondrocytes lose their proliferative activity with aging yet can be restimulated by PTH-(1-84), PGE1, and dexamethasone.
Mouse mandibular condyles develop spontaneous degenerative changes by 6 months of age, hence providing a good in vivo model for studies related to processes associated with the onset and progression of age-related osteoarthritis. Further, this joint provides an appropriate system to investigate the potential of articular cartilage to respond to hormones and local growth factors in old age. The present study examined (1) the age-related changes in [3H]thymidine incorporation by articular chondrocytes in the mouse mandibular condyle, and (2) the effect of systemic and local factors upon the tissue's ability to resume DNA synthesis. Condyles of female CW-1 mice ranging from 3 to 18 months of age were cultured in the presence of PTH-(1-84) (2 micrograms/ml), PGE1 (20 micrograms/ml), dexamethasone (10(-7) M), and MSA (5 micrograms/ml) and were concomitantly labeled with [3H]thymidine. Autoradiographs were analyzed quantitatively and revealed (1) a significant (p less than 0.01) age-related decrease (-80%) in the labeling index of the articular cartilage, and (2) the ability of old tissues to resume DNA synthesis following in vitro treatment with PTH-(1-84), PGE1, and dexamethasone. Concomitant quantitative incorporation studies further substantiated the autoradiographic findings. Hence, these factors possess a direct stimulatory effect upon senescent chondrocytes involved in an advanced stage of spontaneous osteoarthritis.
Livne
E
E
Rappaport Institute for Research in the Medical Sciences, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa.
Weiss
A
A
Silbermann
M
M
D000375:Aging / Q000473:pathology*; D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006651:Histocytochemistry; D008335:Mandibular Condyle / Q000166:cytology / Q000378:metabolism; D051379:Mice; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D010006:Osteoblasts / Q000378:metabolism; D010281:Parathyroid Hormone / Q000494:pharmacology*; D013002:Somatomedins / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism
D010281:Parathyroid Hormone; D013002:Somatomedins; D003907:Dexamethasone; D004247:DNA; D000527:Alprostadil; D013936:Thymidine