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alpha-MSH inhibits TNF-alpha-induced matrix metalloproteinase-13 expression by modulating p38 kinase and nuclear factor kappaB signaling in human chondrosarcoma HTB-94 cells.
Osteoarthritis Cartilage. 2008 Jan; 16(1):115-24.OC

Abstract

OBJECTIVE

Proinflammatory cytokine-induced expression of matrix metalloproteinases (MMPs) is a major cause of arthritic cartilage destruction. The neuropeptide, alpha-melanocyte-stimulating hormone (alpha-MSH), has been detected in the synovial fluid of arthritis patients, where it is thought to play an anti-inflammatory role. Here, we examined whether alpha-MSH acts via downregulation of MMP expression, and sought to elucidate the intracellular signal pathways underlying this effect.

DESIGN

Human chondrosarcoma cell line, HTB-94 (SW1353) was pretreated with or without alpha-MSH and then treated with tumor necrosis factor-alpha (TNF-alpha). The effect of alpha-MSH on TNF-alpha-induced MMP-13 expression and mitogen-activated protein kinases' (MAPKs) activation were determined by reverse transcriptase-polymerase chain reaction and Western blot analysis. Additionally, the intracellular signaling of alpha-MSH was investigated using the inhibitors of MAPK and nuclear factor kappaB (NF-kappaB) and plasmids encoding dominant negative (dn) forms of inhibitor kappaB kinase-alpha (IKKalpha) and inhibitor kappaB kinase-beta (IKKbeta).

RESULTS

We found that alpha-MSH pretreatment inhibited TNF-alpha-induced MMP-13 expression and p38 kinase phosphorylation in HTB-94 human chondrosarcoma cells. TNF-alpha-induced MMP-13 expression was not suppressed by extracellular signal-regulated kinase (ERK) inhibitors (PD98059 and U0126) or a c-jun terminal kinase (JNK) inhibitor (SP600125), but was inhibited by inhibitors of p38 kinase (SB203580) and NF-kappaB (SN-50 peptide) and dnIKKalpha and dnIKKbeta.

CONCLUSIONS

Our results suggest that alpha-MSH regulates TNF-alpha-induced MMP-13 expression by decreasing p38 kinase phosphorylation and subsequent NF-kappaB activation in human chondrocytes and may be an effective inhibitor of MMP-13-mediated collagen degradation, providing new potential opportunities for the development of anti-arthritis therapeutics.

Authors+Show Affiliations

Bionanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejon, Republic of Korea.No 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

17683952

Citation

Yoon, S W., et al. "Alpha-MSH Inhibits TNF-alpha-induced Matrix Metalloproteinase-13 Expression By Modulating P38 Kinase and Nuclear Factor kappaB Signaling in Human Chondrosarcoma HTB-94 Cells." Osteoarthritis and Cartilage, vol. 16, no. 1, 2008, pp. 115-24.
Yoon SW, Chun JS, Sung MH, et al. Alpha-MSH inhibits TNF-alpha-induced matrix metalloproteinase-13 expression by modulating p38 kinase and nuclear factor kappaB signaling in human chondrosarcoma HTB-94 cells. Osteoarthritis Cartilage. 2008;16(1):115-24.
Yoon, S. W., Chun, J. S., Sung, M. H., Kim, J. Y., & Poo, H. (2008). Alpha-MSH inhibits TNF-alpha-induced matrix metalloproteinase-13 expression by modulating p38 kinase and nuclear factor kappaB signaling in human chondrosarcoma HTB-94 cells. Osteoarthritis and Cartilage, 16(1), 115-24.
Yoon SW, et al. Alpha-MSH Inhibits TNF-alpha-induced Matrix Metalloproteinase-13 Expression By Modulating P38 Kinase and Nuclear Factor kappaB Signaling in Human Chondrosarcoma HTB-94 Cells. Osteoarthritis Cartilage. 2008;16(1):115-24. PubMed PMID: 17683952.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - alpha-MSH inhibits TNF-alpha-induced matrix metalloproteinase-13 expression by modulating p38 kinase and nuclear factor kappaB signaling in human chondrosarcoma HTB-94 cells. AU - Yoon,S W, AU - Chun,J S, AU - Sung,M H, AU - Kim,J Y, AU - Poo,H, Y1 - 2007/08/01/ PY - 2006/11/13/received PY - 2007/05/26/accepted PY - 2007/8/9/pubmed PY - 2008/8/15/medline PY - 2007/8/9/entrez SP - 115 EP - 24 JF - Osteoarthritis and cartilage JO - Osteoarthritis Cartilage VL - 16 IS - 1 N2 - OBJECTIVE: Proinflammatory cytokine-induced expression of matrix metalloproteinases (MMPs) is a major cause of arthritic cartilage destruction. The neuropeptide, alpha-melanocyte-stimulating hormone (alpha-MSH), has been detected in the synovial fluid of arthritis patients, where it is thought to play an anti-inflammatory role. Here, we examined whether alpha-MSH acts via downregulation of MMP expression, and sought to elucidate the intracellular signal pathways underlying this effect. DESIGN: Human chondrosarcoma cell line, HTB-94 (SW1353) was pretreated with or without alpha-MSH and then treated with tumor necrosis factor-alpha (TNF-alpha). The effect of alpha-MSH on TNF-alpha-induced MMP-13 expression and mitogen-activated protein kinases' (MAPKs) activation were determined by reverse transcriptase-polymerase chain reaction and Western blot analysis. Additionally, the intracellular signaling of alpha-MSH was investigated using the inhibitors of MAPK and nuclear factor kappaB (NF-kappaB) and plasmids encoding dominant negative (dn) forms of inhibitor kappaB kinase-alpha (IKKalpha) and inhibitor kappaB kinase-beta (IKKbeta). RESULTS: We found that alpha-MSH pretreatment inhibited TNF-alpha-induced MMP-13 expression and p38 kinase phosphorylation in HTB-94 human chondrosarcoma cells. TNF-alpha-induced MMP-13 expression was not suppressed by extracellular signal-regulated kinase (ERK) inhibitors (PD98059 and U0126) or a c-jun terminal kinase (JNK) inhibitor (SP600125), but was inhibited by inhibitors of p38 kinase (SB203580) and NF-kappaB (SN-50 peptide) and dnIKKalpha and dnIKKbeta. CONCLUSIONS: Our results suggest that alpha-MSH regulates TNF-alpha-induced MMP-13 expression by decreasing p38 kinase phosphorylation and subsequent NF-kappaB activation in human chondrocytes and may be an effective inhibitor of MMP-13-mediated collagen degradation, providing new potential opportunities for the development of anti-arthritis therapeutics. SN - 1063-4584 UR - https://www.unboundmedicine.com/medline/citation/17683952/alpha_MSH_inhibits_TNF_alpha_induced_matrix_metalloproteinase_13_expression_by_modulating_p38_kinase_and_nuclear_factor_kappaB_signaling_in_human_chondrosarcoma_HTB_94_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1063-4584(07)00202-6 DB - PRIME DP - Unbound Medicine ER -