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Oncostatin M induces angiogenesis and cartilage degradation in rheumatoid arthritis synovial tissue and human cartilage cocultures.
Arthritis Rheum. 2006 Oct; 54(10):3152-62.AR

Abstract

OBJECTIVE

To investigate the role of oncostatin M (OSM) in cell adhesion, angiogenesis, and matrix degradation in rheumatoid arthritis (RA) synovial tissue and normal human cartilage.

METHODS

Human dermal microvascular endothelial cell (HDMEC) and RA synovial fibroblast (RASF) proliferation and intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expression were assessed by a bromodeoxyuridine proliferation assay and flow cytometry. HDMEC tubule formation and migration were assessed by Matrigel culture and migration assay. Production of matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinases 1 (TIMP-1) in RA synovial explants, and proteoglycan/glycosaminoglycan (GAG) release, vascular endothelial growth factor (VEGF), and angiopoietin 2 production from RASF/normal cartilage cocultures were assessed by enzyme-linked immunosorbent assay and immunohistology.

RESULTS

HDMEC/RASF proliferation was induced by OSM and interleukin-1beta (IL-1beta), alone and in combination. OSM enhanced cell surface expression of ICAM-1, but not VCAM-1, on endothelial cells and RASFs. OSM increased endothelial cell tubule formation and migration. In RA synovial explants, OSM induced production of MMP-1 and TIMP-1. When OSM was combined with IL-1beta, however, the MMP-1:TIMP-1 ratio was significantly increased. OSM potentiated IL-1beta-induced MMP-1 and MMP-13 expression in normal human cartilage/RASF cocultures, resulting in a significant increase in the MMP:TIMP ratio. In OSM/IL-1beta- stimulated cocultures, cartilage sections demonstrated significant proteoglycan depletion that was paralleled by a significant increase in GAG release in supernatants. Finally, compared with either cytokine alone, the combination of OSM and IL-1beta significantly induced VEGF production in RASF/cartilage cocultures.

CONCLUSION

These data suggest that OSM promotes angiogenesis and endothelial cell migration and potentiates the effects of IL-1beta in promoting extracellular matrix turnover and human cartilage degradation. Furthermore, the induction of VEGF in cocultures supports the hypothesis of a link between angiogenesis and cartilage degradation.

Authors+Show Affiliations

St. Vincent's University Hospital and the Conway Institute of Biomolecular and Biomedical Research, Dublin, Ireland.No affiliation info availableNo 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

17009243

Citation

Fearon, Ursula, et al. "Oncostatin M Induces Angiogenesis and Cartilage Degradation in Rheumatoid Arthritis Synovial Tissue and Human Cartilage Cocultures." Arthritis and Rheumatism, vol. 54, no. 10, 2006, pp. 3152-62.
Fearon U, Mullan R, Markham T, et al. Oncostatin M induces angiogenesis and cartilage degradation in rheumatoid arthritis synovial tissue and human cartilage cocultures. Arthritis Rheum. 2006;54(10):3152-62.
Fearon, U., Mullan, R., Markham, T., Connolly, M., Sullivan, S., Poole, A. R., FitzGerald, O., Bresnihan, B., & Veale, D. J. (2006). Oncostatin M induces angiogenesis and cartilage degradation in rheumatoid arthritis synovial tissue and human cartilage cocultures. Arthritis and Rheumatism, 54(10), 3152-62.
Fearon U, et al. Oncostatin M Induces Angiogenesis and Cartilage Degradation in Rheumatoid Arthritis Synovial Tissue and Human Cartilage Cocultures. Arthritis Rheum. 2006;54(10):3152-62. PubMed PMID: 17009243.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oncostatin M induces angiogenesis and cartilage degradation in rheumatoid arthritis synovial tissue and human cartilage cocultures. AU - Fearon,Ursula, AU - Mullan,Ronan, AU - Markham,Trevor, AU - Connolly,Mary, AU - Sullivan,Shane, AU - Poole,A Robin, AU - FitzGerald,Oliver, AU - Bresnihan,Barry, AU - Veale,Douglas J, PY - 2006/9/30/pubmed PY - 2006/12/9/medline PY - 2006/9/30/entrez SP - 3152 EP - 62 JF - Arthritis and rheumatism JO - Arthritis Rheum. VL - 54 IS - 10 N2 - OBJECTIVE: To investigate the role of oncostatin M (OSM) in cell adhesion, angiogenesis, and matrix degradation in rheumatoid arthritis (RA) synovial tissue and normal human cartilage. METHODS: Human dermal microvascular endothelial cell (HDMEC) and RA synovial fibroblast (RASF) proliferation and intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expression were assessed by a bromodeoxyuridine proliferation assay and flow cytometry. HDMEC tubule formation and migration were assessed by Matrigel culture and migration assay. Production of matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinases 1 (TIMP-1) in RA synovial explants, and proteoglycan/glycosaminoglycan (GAG) release, vascular endothelial growth factor (VEGF), and angiopoietin 2 production from RASF/normal cartilage cocultures were assessed by enzyme-linked immunosorbent assay and immunohistology. RESULTS: HDMEC/RASF proliferation was induced by OSM and interleukin-1beta (IL-1beta), alone and in combination. OSM enhanced cell surface expression of ICAM-1, but not VCAM-1, on endothelial cells and RASFs. OSM increased endothelial cell tubule formation and migration. In RA synovial explants, OSM induced production of MMP-1 and TIMP-1. When OSM was combined with IL-1beta, however, the MMP-1:TIMP-1 ratio was significantly increased. OSM potentiated IL-1beta-induced MMP-1 and MMP-13 expression in normal human cartilage/RASF cocultures, resulting in a significant increase in the MMP:TIMP ratio. In OSM/IL-1beta- stimulated cocultures, cartilage sections demonstrated significant proteoglycan depletion that was paralleled by a significant increase in GAG release in supernatants. Finally, compared with either cytokine alone, the combination of OSM and IL-1beta significantly induced VEGF production in RASF/cartilage cocultures. CONCLUSION: These data suggest that OSM promotes angiogenesis and endothelial cell migration and potentiates the effects of IL-1beta in promoting extracellular matrix turnover and human cartilage degradation. Furthermore, the induction of VEGF in cocultures supports the hypothesis of a link between angiogenesis and cartilage degradation. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/17009243/Oncostatin_M_induces_angiogenesis_and_cartilage_degradation_in_rheumatoid_arthritis_synovial_tissue_and_human_cartilage_cocultures_ L2 - https://doi.org/10.1002/art.22161 DB - PRIME DP - Unbound Medicine ER -