Roles of MAP kinases in the regulation of bone matrix gene expressions in human osteoblasts by oscillatory fluid flow

Chia Ching Wu, Yi Shuan Li, Jason H. Haga, Nanping Wang, Ian Y.Z. Lian, Fong Chin Su, Shunichi Usami, Shu Chien

Research output: Contribution to journalArticle

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Abstract

We investigated the effects of oscillatory flow in regulating the gene expressions of type I collagen (COL1, the main component of human bone tissues) and osteopontin (OPN, the key gene for calcium deposition) in human osteoblast-like (MG-63) cells, and the roles of mitogen-activated protein kinases (MAPKs) in this regulation. The cells were subjected to oscillatory flow (0.5 ± 4 dyn/cm2) or kept under static condition for various time periods (15 min, 30 min, 1 h, 2 h, 4 h, 8 h, and 16 h). Oscillatory flow caused significant up-regulations of both COL1 and OPN gene expressions over the 16 h of study, and a transient activation of MAPKs was starting at 15 min and declining to basal level in 2 h. The flow-induction of COL1 was blocked by an ERK inhibitor (PD98059) and reduced by a JNK inhibitor (SP600125), whereas that of OPN was abolished by PD98059. Analysis of the cis-elements in the COL1 and OPN promoters suggests the involvement of transacting factors Elk-1 and AP-1 in the transcription regulation. The ERK inhibitor (PD98059) blocked Elk-1 phosphorylation, as well as COL1 and OPN gene expression. The JNK inhibitor (SP600125) abolished c-jun phosphorylation and COL1 expression. These results suggest that the flow-induction of OPN was mediated through the ERK-Elk1-OPN pathway, and that COL1 was regulated by both the ERK-Elk1-COL1 and JNK-c-JUN-COL1 pathway.

Original languageEnglish
Pages (from-to)632-641
Number of pages10
JournalJournal of Cellular Biochemistry
Volume98
Issue number3
DOIs
Publication statusPublished - 2006 Jun 1

Fingerprint

Bone Matrix
Osteoblasts
Gene expression
Flow of fluids
Bone
Phosphorylation
Phosphotransferases
Mitogen-Activated Protein Kinases
Gene Expression
Osteopontin
Transcription Factor AP-1
Transcription
Collagen Type I
Up-Regulation
Genes
Chemical activation
Tissue
Calcium
Bone and Bones
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Wu, Chia Ching ; Li, Yi Shuan ; Haga, Jason H. ; Wang, Nanping ; Lian, Ian Y.Z. ; Su, Fong Chin ; Usami, Shunichi ; Chien, Shu. / Roles of MAP kinases in the regulation of bone matrix gene expressions in human osteoblasts by oscillatory fluid flow. In: Journal of Cellular Biochemistry. 2006 ; Vol. 98, No. 3. pp. 632-641.
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Roles of MAP kinases in the regulation of bone matrix gene expressions in human osteoblasts by oscillatory fluid flow. / Wu, Chia Ching; Li, Yi Shuan; Haga, Jason H.; Wang, Nanping; Lian, Ian Y.Z.; Su, Fong Chin; Usami, Shunichi; Chien, Shu.

In: Journal of Cellular Biochemistry, Vol. 98, No. 3, 01.06.2006, p. 632-641.

Research output: Contribution to journalArticle

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AU - Wu, Chia Ching

AU - Li, Yi Shuan

AU - Haga, Jason H.

AU - Wang, Nanping

AU - Lian, Ian Y.Z.

AU - Su, Fong Chin

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AU - Chien, Shu

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AB - We investigated the effects of oscillatory flow in regulating the gene expressions of type I collagen (COL1, the main component of human bone tissues) and osteopontin (OPN, the key gene for calcium deposition) in human osteoblast-like (MG-63) cells, and the roles of mitogen-activated protein kinases (MAPKs) in this regulation. The cells were subjected to oscillatory flow (0.5 ± 4 dyn/cm2) or kept under static condition for various time periods (15 min, 30 min, 1 h, 2 h, 4 h, 8 h, and 16 h). Oscillatory flow caused significant up-regulations of both COL1 and OPN gene expressions over the 16 h of study, and a transient activation of MAPKs was starting at 15 min and declining to basal level in 2 h. The flow-induction of COL1 was blocked by an ERK inhibitor (PD98059) and reduced by a JNK inhibitor (SP600125), whereas that of OPN was abolished by PD98059. Analysis of the cis-elements in the COL1 and OPN promoters suggests the involvement of transacting factors Elk-1 and AP-1 in the transcription regulation. The ERK inhibitor (PD98059) blocked Elk-1 phosphorylation, as well as COL1 and OPN gene expression. The JNK inhibitor (SP600125) abolished c-jun phosphorylation and COL1 expression. These results suggest that the flow-induction of OPN was mediated through the ERK-Elk1-OPN pathway, and that COL1 was regulated by both the ERK-Elk1-COL1 and JNK-c-JUN-COL1 pathway.

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