Effect of parathyroid hormone on type X and type II collagen expression in mesenchymal stem cells from osteoarthritic patients.
A major drawback of current cartilage and intervertebral disc tissue engineering is that human mesenchymal stem cells (MSCs) from osteoarthritic (OA) patients express type X collagen (COL10), a marker of late-stage chondrocyte hypertrophy (associated with endochondral ossification). Parathyroid hormone (PTH) regulates endochondral ossification by inhibiting chondrocyte differentiation toward hypertrophy. In this study, we investigated the effect of PTH on expression of COL10 in MSCs from OA patients and analyzed the potential mechanisms related to its effect. MSCs were obtained from aspirates from the intramedullary canal of donors undergoing total hip replacement for OA. Expanded cells were then incubated for 0-48  h without (control) or with 100  nM PTH (1-34). Protein expression and phosphorylation were measured by Western blot. Results showed that PTH (1-34) inhibited expression of COL10 in MSCs from OA patients in a time-dependent manner. In parallel, PTH (1-34) stimulated expression of COL2, a marker of chondrogenic differentiation. Results also showed that PTH (1-34) inhibited in a sustained manner the phosphorylation of p38 and AKT protein kinase signaling pathways. Interestingly, the modulation of COL2 and COL10 gene expression was significant as rapidly as after 1  h in the presence of PTH (1-34); changes in the phosphorylation of p38 and AKT were significant only after 6  h. This suggests that while p38 and AKT protein kinase signaling pathways may not be required to initiate the regulation of expression of COL2 and COL10 by PTH (1-34), these pathways may modulate later events necessary for preventing precocious MSC hypertrophy.
Mwale
Fackson
F
Division of Orthopaedic Surgery, McGill University, Montreal, Canada. fmwale@ldi.jgh.mcgill.ca
Yao
Guoying
G
Ouellet
Jean A
JA
Petit
Alain
A
Antoniou
John
J
D000368:Aged; D000369:Aged, 80 and over; D024042:Collagen Type I / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism*; D024121:Collagen Type X / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D024042:Collagen Type I; D024043:Collagen Type II; D024121:Collagen Type X; D010281:Parathyroid Hormone; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases