Dual transduction of insulin-like growth factor-I and interleukin-1 receptor antagonist protein controls cartilage degradation in an osteoarthritic culture model
- PMID: 15607883
- DOI: 10.1016/j.orthres.2004.06.020
Dual transduction of insulin-like growth factor-I and interleukin-1 receptor antagonist protein controls cartilage degradation in an osteoarthritic culture model
Abstract
This study evaluated the potential of gene induced synoviocyte expression of a combination of insulin-like growth factor-I (AdIGF-I) and interleukin-1 receptor antagonist protein (AdIL-1Ra) to control articular cartilage degradation in vitro. Cartilage explants and synovial membrane were harvested from young mature horses. Synovial monolayers were established and either (1) maintained as untransduced controls; (2) transduced with AdIGF-I at 200 MOI in 500 microl serum-free medium; (3) transduced with AdIL-1Ra at 100 MOI; or (4) transduced with a combination of AdIGF-I (200 MOI) and AdIL-1Ra (100 MOI). Following transduction, cartilage explants were exposed to the synovial monolayer medium using co-culture inserts. Cultures were maintained for 6 days in either serum-free medium or medium containing 10 ng/ml recombinant human interleukin-1beta. At termination, synovial cell RNA was isolated for real-time PCR analysis, and cartilage explants were collected for H&E and toluidine blue staining, immunohistochemistry for type II collagen and IGF-I, in situ localization of IGF-I and type II collagen gene expression, and biochemical assays. Synovial monolayers were readily transduced with both AdIGF-I and AdIL-1Ra. IGF-I and IL-1Ra protein were secreted at beneficial levels throughout the experiment, having peak concentrations of 94.6 ng/ml and 33.0 ng/ml, respectively. Transduction with IGF-I promoted cartilage production of proteoglycan and type II collagen, suggesting a beneficial role for healing injured cartilage. Transduction with IL-1Ra decreased the synovial expression of IL-1alpha and IL-1beta and matrix metalloproteinases, indicating a mechanism for prevention of matrix degradation. The beneficial effects of the combination of anabolic growth factors and catabolic blockers were evident in improved preservation of proteoglycan content of cartilage explants exposed to the depleting effects of IL-1. These results show that gene therapy combining anabolic growth factors to stimulate matrix synthesis and catabolic blockers to prevent matrix degradation by IL-1, protects and causes partial restoration of cartilage matrix, and suggest a potential benefit of combination gene therapy for cartilage healing.
Similar articles
-
Gene-mediated restoration of cartilage matrix by combination insulin-like growth factor-I/interleukin-1 receptor antagonist therapy.Gene Ther. 2005 Jan;12(2):177-86. doi: 10.1038/sj.gt.3302396. Gene Ther. 2005. PMID: 15578043
-
Gene mediated insulin-like growth factor-I delivery to the synovium.J Orthop Res. 2001 Sep;19(5):759-67. doi: 10.1016/S0736-0266(00)00077-2. J Orthop Res. 2001. PMID: 11562119
-
Insulin-like growth factor 1 and corticosteroid modulation of chondrocyte metabolic and mitogenic activities in interleukin 1-conditioned equine cartilage.Am J Vet Res. 1997 May;58(5):524-30. Am J Vet Res. 1997. PMID: 9140562
-
[Regulation of cartilage matrix synthesis by chondrocytes].Rev Rhum Ed Fr. 1994 Nov 15;61(9 Pt 2):93S-98S. Rev Rhum Ed Fr. 1994. PMID: 7858613 Review. French.
-
Gene therapy in musculoskeletal repair.Ann N Y Acad Sci. 2007 Nov;1117:310-27. doi: 10.1196/annals.1402.065. Ann N Y Acad Sci. 2007. PMID: 18056051 Review.
Cited by
-
The role of the immune microenvironment in bone, cartilage, and soft tissue regeneration: from mechanism to therapeutic opportunity.Mil Med Res. 2022 Nov 19;9(1):65. doi: 10.1186/s40779-022-00426-8. Mil Med Res. 2022. PMID: 36401295 Free PMC article. Review.
-
Use of tissue engineering strategies to repair joint tissues in osteoarthritis: viral gene transfer approaches.Curr Rheumatol Rep. 2014 Oct;16(10):449. doi: 10.1007/s11926-014-0449-0. Curr Rheumatol Rep. 2014. PMID: 25182677 Review.
-
Biokinetic Mechanisms Linked With Musculoskeletal Health Disparities: Stochastic Models Applying Tikhonov's Theorem to Biomolecule Homeostasis.J Nanotechnol Eng Med. 2011 May 1;2(2):21004-21012. doi: 10.1115/1.4003876. J Nanotechnol Eng Med. 2011. PMID: 21743831 Free PMC article.
-
CypB-CD147 Signaling Is Involved in Crosstalk between Cartilage and FLS in Collagen-Induced Arthritis.Mediators Inflamm. 2020 Aug 29;2020:6473858. doi: 10.1155/2020/6473858. eCollection 2020. Mediators Inflamm. 2020. PMID: 32908452 Free PMC article.
-
Effects of adenovirus-mediated bFGF, IL-1Ra and IGF-1 gene transfer on human osteoarthritic chondrocytes and osteoarthritis in rabbits.Exp Mol Med. 2010 Oct 31;42(10):684-95. doi: 10.3858/emm.2010.42.10.067. Exp Mol Med. 2010. PMID: 20733349 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical