Transforming growth factor-alpha induces endothelin receptor A expression in osteoarthritis
- PMID: 22407503
- DOI: 10.1002/jor.22099
Transforming growth factor-alpha induces endothelin receptor A expression in osteoarthritis
Abstract
Previously, our lab identified transforming growth factor-alpha (TGFα) as a novel factor involved in osteoarthritis (OA) in a surgical model of the disease. In the same study, we also observed increased transcript levels for endothelin receptor A (ET(A)R), a known contributor to cartilage pathology. To investigate the connection between TGFα and endothelin signaling in OA, primary articular chondrocytes and osteochondral explants were isolated from Sprague-Dawley rats and treated with vehicle or TGFα. Expression of ET(A)R protein and its encoding gene Ednra was assessed. Chondrocytes and cartilage explants were also treated with the endothelin receptor A/B antagonist Bosentan, in order to determine whether TGFα effects could be blocked. TGFα induced expression of ET(A)R protein and its encoding gene Ednra. In primary chondrocyte cultures, Bosentan did not block TGFα responses of the anabolic genes Sox9, Agc1, and Col2a1, but reduced the induction of Mmp13 and Ednra transcripts by TGFα. In osteochondral explants, the inhibitor partially blocked TGFα reduction of type II collagen, as well as induction of MMP-13 and type II collagen neoepitopes. TGFα induces ET(A)R expression in articular chondrocytes and receptor antagonism appears to block some TGFα-induced catabolic effects in a three-dimensional organ culture system. Thus, TGFα may be a therapeutic target upstream of ET(A)R in OA.
Copyright © 2012 Orthopaedic Research Society.
Similar articles
-
Reduction in disease progression by inhibition of transforming growth factor α-CCL2 signaling in experimental posttraumatic osteoarthritis.Arthritis Rheumatol. 2015 Oct;67(10):2691-701. doi: 10.1002/art.39255. Arthritis Rheumatol. 2015. PMID: 26138996
-
Rho/ROCK and MEK/ERK activation by transforming growth factor-alpha induces articular cartilage degradation.Lab Invest. 2010 Jan;90(1):20-30. doi: 10.1038/labinvest.2009.111. Epub 2009 Oct 12. Lab Invest. 2010. PMID: 19823173
-
Transforming growth factor alpha suppression of articular chondrocyte phenotype and Sox9 expression in a rat model of osteoarthritis.Arthritis Rheum. 2007 Nov;56(11):3693-705. doi: 10.1002/art.22968. Arthritis Rheum. 2007. PMID: 17968906
-
Prostaglandin PGE2 at very low concentrations suppresses collagen cleavage in cultured human osteoarthritic articular cartilage: this involves a decrease in expression of proinflammatory genes, collagenases and COL10A1, a gene linked to chondrocyte hypertrophy.Arthritis Res Ther. 2007;9(4):R75. doi: 10.1186/ar2273. Arthritis Res Ther. 2007. PMID: 17683641 Free PMC article.
-
The role of cytokines in osteoarthritis pathophysiology.Biorheology. 2002;39(1-2):237-46. Biorheology. 2002. PMID: 12082286 Review.
Cited by
-
MicroRNA-183 attenuates osteoarthritic pain by inhibiting the TGFα-mediated CCL2/CCR2 signalling axis.Bone Joint Res. 2021 Aug;10(8):548-557. doi: 10.1302/2046-3758.108.BJR-2019-0308.R2. Bone Joint Res. 2021. PMID: 34463129 Free PMC article.
-
Role of iRhoms 1 and 2 in Endochondral Ossification.Int J Mol Sci. 2020 Nov 19;21(22):8732. doi: 10.3390/ijms21228732. Int J Mol Sci. 2020. PMID: 33227998 Free PMC article.
-
Context-specific protection of TGFα null mice from osteoarthritis.Sci Rep. 2016 Jul 26;6:30434. doi: 10.1038/srep30434. Sci Rep. 2016. PMID: 27457421 Free PMC article.
-
Transient anabolic effects accompany epidermal growth factor receptor signal activation in articular cartilage in vivo.Arthritis Res Ther. 2013;15(3):R60. doi: 10.1186/ar4233. Arthritis Res Ther. 2013. PMID: 23705804 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous