Several members of the TGF-β super family play important roles in connective tissue growth. The bone morphogenetic proteins (BMPs) induce early cartilage formation and MMP13 is a major enzyme targeting cartilage for the degradation of types II, IV, and IX collagen, proteoglycan, osteonectin and perlecan. In this review, we discuss the crosstalk between SMAD/TGF-β signalling pathway and therapeutic applications in connective tissue diseases.
Keywords: SATF3; Endotoxemia; Proinflammatory cytokine; HMGB1
Copyright © 2021 by The American Society for BioMedicine and BM-Publisher, Inc.
- Pombo-Suarez M, Castano-Oreja MT, Calaza M, Gomez-Reino J, Gonzalez A. Differential upregulation of the three transforming growth factor beta isoforms in human osteoarthritic cartilage. Ann Rheum Dis 2009; 68:568-71.
- Verdier MP, Seite S, Guntzer K, Pujol JP, Boumediene K. Immunohistochemical analysis of transforming growth factor beta isoforms and their receptors in human cartilage from normal and osteoarthritic femoral heads. Rheumatol Int 2005; 25:118-24.
- Moldovan F, Pelletier JP, Hambor J, Cloutier JM, Martel-Pelletier J. Collagenase-3 (matrix metalloprotease 13) is preferentially localized in the deep layer of human arthritic cartilage in situ: in vitro mimicking effect by transforming growth factor beta. Arthritis Rheum 1997; 40:1653-61.
- Selvamurugan N, Kwok S, Alliston T, Reiss M, Partridge NC. Transforming growth factor-beta 1 regulation of collagenase-3 expression in osteoblastic cells by cross-talk between the Smad and MAPK signaling pathways and their components, Smad2 and Runx2. J Biol Chem 2004; 279:19327-34.
- Cawston T, Billington C, Cleaver C, et al. The regulation of MMPs and TIMPs in cartilage turnover. Annu. NY Acad. Sci 1999;878:120-129.
- Yanga x, Chena L, Xu x, et al. TGF-β/Smad3 signals repress chondrocyte hypertrophic differentiation and are required for maintaining articular cartilage. JCB 2001;153:35-46.
- Giordano M, Valentini G, Migliaresi S, Picillo U, Vatti M. Different antibody patterns and different prognoses in patients with scleroderma with various extent of skin sclerosis. J Rheumatol 1986;13:911-916.
- Flam ST, Gunnarsson R, Garen T, Norwegian MSG, Lie BA, Molberg O. The HLA profiles of mixed connective tissue disease differ distinctly from the profiles of clinically related connective tissue diseases. Rheumatol 2015; 54:528-535.
- Swanton J, Isenberg D. Mixed connective tissue disease: still crazy after all these years. Rheum Dis Clin N Am 2005; 31:421-436.
- Ortega-Hernandez OD, Shoenfeld Y. Mixed connective tissue disease: an overview of clinical manifestations, diagnosis and treatment. Best Pract Res Clin Rheumatol 2012; 26:61-72.
- Seppinen L, Pihlajaniemi T. The multiple functions of collagen XVIII in development and disease. Matrix Biol 2011; 30:83-92.
- Dziankowska-Bartkowiak B, Waszczykowska E, Zalewska A, Sysa-Jedrzejowska A. Correlation of endostatin and tissue inhibitor of metalloproteinases 2 (TIMP2) serum levels with cardiovascular involvement in systemic sclerosis patients. Mediat Inflamm 2005; 2005:144-149.
- Peng WJ, Yan JW, Wan YN, et al. Matrix metalloproteinases: a review of their structure and role in systemic sclerosis. J Clin Immunol 2012; 32:1409-1414.
- Hajas A, Szodoray P, Nakken B, et al. Clinical course, prognosis, and causes of death in mixed connective tissue disease. J Rheumatol 2013; 40:1134-1142.
- Xiang X, Chen L, Xu X, Li C, Huang C, Deng CX. TGF-beta/Smad3 signals repress chondrocyte hypertrophic differentiation and are required for maintaining articular cartilage. J Cell Biol 2001; 153:35-46.
- Blaney Davidson EN, Scharstuhl A, Vitters EL, van der Kraan PM, van den Berg WB. Reduced transforming growth factor-beta signaling in cartilage of old mice: role in impaired repair capacity. Arthritis Res Ther 2005; 7:R1338-1347.
- Blaney Davidson EN, Vitters EL, van der Kraan PM, van den Berg WB. Expression of transforming growth factor-beta (TGFbeta) and the TGFbeta signalling molecule SMAD-2P in spontaneous and instability-induced osteoarthritis: role in cartilage degradation, chondrogenesis and osteophyte formation. Ann Rheum Dis 2006; 65:1414-21.
- van der Kraan PM. Age-related alterations in TGF beta signaling as a causal factor of cartilage degeneration in osteoarthritis. Biomed Mater Eng 2014; 24:75-80.
- Janssen NM, Karnad DR, Guntupalli KK. Rheumatologic diseases in the intensive care unit: epidemiology, clinical approach, management, and outcome. Crit Care Clin 2002;18(4):729-48.
- Mengshol JA, Vincenti MP, Brinckerhoff CE. IL-1 induces collagenase-3 (MMP-13) promoter activity in stably transfected chondrocytic cells: requirement for Runx-2 and activation by p38 MAPK and JNK pathways. Nucleic Acids Res 2001; 29:4361-72.
- Cheon H, Yu SJ, Yoo DH, Chae IJ, Song GG, Sohn J. Increased expression of pro-inflammatory cytokines and metalloproteinase-1 by TGF-beta1 in synovial fibroblasts from rheumatoid arthritis and normal individuals. Clin Exp Immunol 2002; 127:547-52.
For any technique error please contact us
American Journal of BioMedicine 2021, Volume 9, Issue 2, pages 110-121
Received December 12, 2020; revised April 06, 2021; accepted May 01, 2021; published May 11, 2021
How to cite this article
Li X, Bronner M, Ribeiro JA, Oliveira K. Role of SMAD/TGF-β signaling pathway in connective tissue diseases. American Journal of BioMedicine 2021;9(2):110-121.