A novel terminal differentiation model of human articular chondrocytes in three-dimensional cultures mimicking chondrocytic changes in osteoarthritis.
This study establishes a cell culture model mimicking the terminal differentiation occurring in osteoarthritic chondrocytes. Normal articular chondrocytes obtained from human knees treated with 5-azacytidine (Aza-C) were harvested 3, 7 and 14 days after treatment. Phenotypic and genetic changes of articular chondrocytes were detected. The results show that mRNA expression of collagen type II, a marker for normal functional articular chondrocytes, was significantly decreased after Aza-C treatment in comparison to the control cultures, while those of collagen type X and ALP, markers for hypertrophic chondrocytes, were significantly increased. Cell size and apoptotic rate of articular chondrocytes showed significant increases compared to the control after 14 days of Aza-C treatment. Terminal differentiation is shown by this model of three-dimensional cultured human articular chondrocytes, which could apply to the studies of the cellular mechanisms of osteoarthritis.
Ho
Mei-Ling
ML
Department of Physiology, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Chang
Je-Ken
JK
Wu
Shun-Cheng
SC
Chung
Ya-Hui
YH
Chen
Chung-Hwan
CH
Hung
Shao-Hung
SH
Wang
Gwo-Jaw
GJ
D000469:Alkaline Phosphatase / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects; D001374:Azacitidine / Q000494:pharmacology; D002358:Cartilage, Articular / Q000166:cytology*; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D048429:Cell Size / Q000187:drug effects; D019902:Chondrocytes / Q000378:metabolism*; D024043:Collagen Type II / Q000235:genetics; D024121:Collagen Type X / Q000235:genetics; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020287:In Situ Nick-End Labeling; D008954:Models, Biological; D010003:Osteoarthritis / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D024043:Collagen Type II; D024121:Collagen Type X; D012333:RNA, Messenger; D000469:Alkaline Phosphatase; D001374:Azacitidine