Induction of chondrogenic phenotype in synovium-derived progenitor cells by intermittent hydrostatic pressure.
OBJECTIVE
The aim of this study was to investigate the effect of intermittent hydrostatic pressure (IHP) on chondrogenic differentiation of synovium-derived progenitor cells (SPCs).


METHODS
SPCs, bone marrow-derived progenitor cells and skin fibroblasts from rabbits were subjected to IHP ranging from 1.0 to 5.0 MPa. The mRNA expression of proteoglycan core protein (PG), collagen type II and SOX-9 was examined using real-time reverse transcriptase-polymerase chain reaction (RT-PCR). The production of SOX-9 protein and glycosaminoglycan (GAG) by SPCs was analyzed by Western blot and the dimethylmethylene blue assay. In addition, mitogen-activated protein (MAP) kinase inhibitors for c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and the p38 pathway were used to identify the signal transduction pathways.


RESULTS
Real-time RT-PCR showed that mRNA expression of PG, collagen type II and SOX-9 was significantly enhanced only in SPCs receiving 5.0 MPa of IHP. The production of SOX-9 protein and GAG by SPCs was also increased by exposure to 5.0 MPa of IHP. These up-regulated expressions were suppressed by pretreatment with an inhibitor of JNK, but not with inhibitors of ERK or p38.


CONCLUSIONS
Our results demonstrated that the exposure of SPCs to 5.0 MPa of IHP could facilitate induction of the chondrogenic phenotype by the MAP kinase/JNK pathway. This finding suggests the potential for IHP utilization in regenerative treatments for cartilage injuries or osteoarthritis.
Sakao
K
K
Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan.
Takahashi
K A
KA
Arai
Y
Y
Inoue
A
A
Tonomura
H
H
Saito
M
M
Yamamoto
T
T
Kanamura
N
N
Imanishi
J
J
Mazda
O
O
Kubo
T
T
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000502:physiology*; D024043:Collagen Type II / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology; D006025:Glycosaminoglycans / Q000096:biosynthesis; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006874:Hydrostatic Pressure; D008297:Male; D040542:Mechanotransduction, Cellular / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D010641:Phenotype; D011509:Proteoglycans / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D055758:SOX9 Transcription Factor / Q000096:biosynthesis / Q000235:genetics; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013314:Stress, Mechanical; D013583:Synovial Membrane / Q000166:cytology* / Q000378:metabolism
D024043:Collagen Type II; D006025:Glycosaminoglycans; D011509:Proteoglycans; D012333:RNA, Messenger; D055758:SOX9 Transcription Factor; D020928:Mitogen-Activated Protein Kinases