Parathyroid hormone 1-34 reduces dexamethasone-induced terminal differentiation in human articular chondrocytes.
Intra-articular injection of dexamethasone (Dex) is occasionally used to relieve pain and inflammation in osteoarthritis (OA) patients. Dex induces terminal differentiation of chondrogenic mesenchymal stem cells in vitro and causes impaired longitudinal skeletal growth in vivo. Parathyroid hormone 1-34 (PTH 1-34) has been shown to reverse terminal differentiation of osteoarthritic articular chondrocytes. We hypothesized that Dex induces terminal differentiation of articular chondrocytes and that this effect can be mitigated by PTH 1-34 treatment. We tested the effect of Dex on terminal differentiation in human articular chondrocytes and further tested if PTH 1-34 reverses the effects. We found that Dex treatment downregulated chondrogenic-induced expressions of SOX-9, collagen type IIa1 (Col2a1), and aggrecan and reduced synthesis of cartilaginous matrix (Col2a1 and sulfated glycosaminoglycan) synthesis. Dex treatment upregulated chondrocyte hypertrophic markers of collagen type X and alkaline phosphatase at mRNA and protein levels, and it increased the cell size of articular chondrocytes and induced cell death. These results indicated that Dex induces terminal differentiation of articular chondrocytes. To test whether PTH 1-34 treatment reverses Dex-induced terminal differentiation of articular chondrocytes, PTH 1-34 was co-administered with Dex. Results showed that PTH 1-34 treatment reversed both changes of chondrogenic and hypertrophic markers in chondrocytes induced by Dex. PTH 1-34 also decreased Dex-induced cell death. PTH 1-34 treatment reduces Dex-induced terminal differentiation and apoptosis of articular chondrocytes, and PTH 1-34 treatment may protect articular cartilage from further damage when received Dex administration.
Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Ling-Hua
LH
Chang
Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Shun-Cheng
SC
Wu
Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Orthopaedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Chung-Hwan
CH
Chen
Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Gwo-Jaw
GJ
Wang
Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Orthopaedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: jkchang@kmu.edu.tw.
Je-Ken
JK
Chang
Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Physiology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, Taiwan. Electronic address: homelin@kmu.edu.tw.
Mei-Ling
ML
Ho
D053674:Aggrecans / Q000235:genetics / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D044466:Asian People; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects*; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D024121:Collagen Type X / Q000235:genetics / Q000378:metabolism; D003907:Dexamethasone / Q000633:toxicity*; D015536:Down-Regulation; D006025:Glycosaminoglycans; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D010281:Parathyroid Hormone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D055815:Young Adult
C508319:ACAN protein, human; D053674:Aggrecans; C499177:COL2A1 protein, human; D024043:Collagen Type II; D024121:Collagen Type X; D006025:Glycosaminoglycans; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; C013786:A73025; D003907:Dexamethasone; D000469:Alkaline Phosphatase
Chondrocyte; Dexamethasone; Osteoarthritis; Parathyroid hormone; Terminal differentiation