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MEK/ERK and signal transducer and activator of transcription signaling pathways modulate oncostatin M-stimulated CCL2 expression in human osteoblasts through a common transcription factor.
Arthritis Rheum. 2004 Mar; 50(3):785-93.AR

Abstract

OBJECTIVE

To analyze the effects of oncostatin M (OSM), a gp130-type cytokine, on CCL2 expression in MG-63 cells, a human osteosarcoma cell line with a characteristic osteoblastic phenotype, and to investigate the signaling pathway involved.

METHODS

The expression of messenger RNA (mRNA) for CCL2 and c-Fos was analyzed by Northern blotting. Amounts of CCL2 released into the supernatant were measured by enzyme-linked immunosorbent assay. Western blotting was used to examine the activation of MAPK signaling pathways. Interactions between activator protein 1 (AP-1) and DNA were evaluated by electrophoretic mobility shift assay.

RESULTS

OSM stimulated CCL2 expression at both the mRNA and the protein levels. Cyclooxygenase 2 (COX-2) was also induced by OSM. However, the up-regulation of CCL2 mRNA was COX-2-independent but required tyrosine kinase and protein kinase C (PKC). OSM stimulated the phosphorylation of MEK-1/2 and ERK-1/2 but not p38 and JNK. A transient elevation of c-Fos mRNA was induced by OSM, but PD 98059 (MEK inhibitor), fludarabine (signal transducer and activator of transcription 1 [STAT-1] inhibitor), and piceatannol (STAT-3 and STAT-5 inhibitor) abolished this effect. Electrophoretic mobility shift assay revealed that OSM stimulated AP-1-DNA binding, which was also abolished by PD 98059, fludarabine, and piceatannol. Supershift study further confirmed the role of c-Fos in the above interaction. PD 98059, fludarabine, piceatannol, and curcumin (AP-1 inhibitor) inhibited the OSM-induced expression of CCL2.

CONCLUSION

OSM induces CCL-2 expression in osteoblasts. Activation of the MEK/ERK and STAT pathways, which leads to c-Fos expression and AP-1-DNA binding, is involved in the process. The signaling requires tyrosine kinase and PKC but not COX-2.

Authors+Show Affiliations

National Taiwan University Hospital, Taipei, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15022320

Citation

Lin, Sze-Kwan, et al. "MEK/ERK and Signal Transducer and Activator of Transcription Signaling Pathways Modulate Oncostatin M-stimulated CCL2 Expression in Human Osteoblasts Through a Common Transcription Factor." Arthritis and Rheumatism, vol. 50, no. 3, 2004, pp. 785-93.
Lin SK, Kok SH, Yeh FT, et al. MEK/ERK and signal transducer and activator of transcription signaling pathways modulate oncostatin M-stimulated CCL2 expression in human osteoblasts through a common transcription factor. Arthritis Rheum. 2004;50(3):785-93.
Lin, S. K., Kok, S. H., Yeh, F. T., Kuo, M. Y., Lin, C. C., Wang, C. C., Goldring, S. R., & Hong, C. Y. (2004). MEK/ERK and signal transducer and activator of transcription signaling pathways modulate oncostatin M-stimulated CCL2 expression in human osteoblasts through a common transcription factor. Arthritis and Rheumatism, 50(3), 785-93.
Lin SK, et al. MEK/ERK and Signal Transducer and Activator of Transcription Signaling Pathways Modulate Oncostatin M-stimulated CCL2 Expression in Human Osteoblasts Through a Common Transcription Factor. Arthritis Rheum. 2004;50(3):785-93. PubMed PMID: 15022320.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MEK/ERK and signal transducer and activator of transcription signaling pathways modulate oncostatin M-stimulated CCL2 expression in human osteoblasts through a common transcription factor. AU - Lin,Sze-Kwan, AU - Kok,Sang-Heng, AU - Yeh,Flora Tzu-Chin, AU - Kuo,Mark Yen-Ping, AU - Lin,Ching-Chuan, AU - Wang,Chih-Chiang, AU - Goldring,Steven R, AU - Hong,Chi-Yuan, PY - 2004/3/17/pubmed PY - 2004/4/10/medline PY - 2004/3/17/entrez SP - 785 EP - 93 JF - Arthritis and rheumatism JO - Arthritis Rheum VL - 50 IS - 3 N2 - OBJECTIVE: To analyze the effects of oncostatin M (OSM), a gp130-type cytokine, on CCL2 expression in MG-63 cells, a human osteosarcoma cell line with a characteristic osteoblastic phenotype, and to investigate the signaling pathway involved. METHODS: The expression of messenger RNA (mRNA) for CCL2 and c-Fos was analyzed by Northern blotting. Amounts of CCL2 released into the supernatant were measured by enzyme-linked immunosorbent assay. Western blotting was used to examine the activation of MAPK signaling pathways. Interactions between activator protein 1 (AP-1) and DNA were evaluated by electrophoretic mobility shift assay. RESULTS: OSM stimulated CCL2 expression at both the mRNA and the protein levels. Cyclooxygenase 2 (COX-2) was also induced by OSM. However, the up-regulation of CCL2 mRNA was COX-2-independent but required tyrosine kinase and protein kinase C (PKC). OSM stimulated the phosphorylation of MEK-1/2 and ERK-1/2 but not p38 and JNK. A transient elevation of c-Fos mRNA was induced by OSM, but PD 98059 (MEK inhibitor), fludarabine (signal transducer and activator of transcription 1 [STAT-1] inhibitor), and piceatannol (STAT-3 and STAT-5 inhibitor) abolished this effect. Electrophoretic mobility shift assay revealed that OSM stimulated AP-1-DNA binding, which was also abolished by PD 98059, fludarabine, and piceatannol. Supershift study further confirmed the role of c-Fos in the above interaction. PD 98059, fludarabine, piceatannol, and curcumin (AP-1 inhibitor) inhibited the OSM-induced expression of CCL2. CONCLUSION: OSM induces CCL-2 expression in osteoblasts. Activation of the MEK/ERK and STAT pathways, which leads to c-Fos expression and AP-1-DNA binding, is involved in the process. The signaling requires tyrosine kinase and PKC but not COX-2. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/15022320/MEK/ERK_and_signal_transducer_and_activator_of_transcription_signaling_pathways_modulate_oncostatin_M_stimulated_CCL2_expression_in_human_osteoblasts_through_a_common_transcription_factor_ L2 - https://doi.org/10.1002/art.20058 DB - PRIME DP - Unbound Medicine ER -