Age-related effects of TGF-beta on proteoglycan synthesis in equine articular cartilage.
Abstract: The synthesis of proteoglycans was measured in normal equine articular cartilage of ages 9 months to 20 years and the effect of TGF-beta1 on this activity was investigated. The rate of incorporation of [(35)S]Na(2)SO(4) decreased with age as did the responsiveness of the tissue to the growth factor. The enhanced synthesis of proteoglycan induced at all ages by TGF-beta1 was down-regulated by IL-1 beta and retinoic acid. The expression of mRNA for TGF-beta1, 2, and 3 was also measured, and although the level of TGF-beta1 was highest at all ages, the expression of each growth factor decreased with age.
Copyright 2000 Academic Press.
Publication Date: 2000-07-29 PubMed ID: 10913361DOI: 10.1006/bbrc.2000.3167Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article explores how aging affects the production of proteoglycans in horse joint cartilage, and how TGF-beta1, an important growth factor, influences this process. Over time, both the natural production of proteoglycans and the impact of TGF-beta1 decrease.
Understanding the Context
- In this research, the synthesis, or production, of proteoglycans in equine articular cartilage is examined. Proteoglycans are proteins that play a crucial role in maintaining the structural integrity of tissues, including cartilage. Articular cartilage is the smooth, white tissue that covers the ends of bones where they come together to form joints.
- The focus of the study is on how age affects proteoglycan synthesis and the activity of TGF-beta1, a type of transforming growth factor that stimulates cell growth, proliferation, and differentiation.
Key Findings
- The research found that as age increases, the rate of proteoglycan synthesis decreases. This was determined by measuring the incorporation of a radioactive isotope, [(35)S]Na(2)SO(4), which was used to trace the process of proteoglycan synthesis.
- Additionally, it was found that the effectiveness of TGF-beta1 in stimulating proteoglycan synthesis also decreases with age. This suggests that aging not only reduces the natural synthesis of proteoglycan, but also the extent to which it can be boosted by TGF-beta1.
- TGF-beta1’s effect in enhancing proteoglycan synthesis was found to be down-regulated, or diminished, by IL-1 beta and retinoic acid, providing a potential explanation for its decreased efficacy in older age.
Measurements of TGF-beta
- The research also involved measuring the expression levels of mRNA for TGF-beta1, 2, and 3. mRNA is a type of RNA that translates the genetic information from DNA into proteins, of which TGF-beta is one type.
- While the level of TGF-beta1 was highest at all ages, the expression of each growth factor decreased with age. This further supports the observation of a decline in TGF-beta efficacy and proteoglycan synthesis with increasing age.
Cite This Article
APA
Iqbal J, Dudhia J, Bird JL, Bayliss MT.
(2000).
Age-related effects of TGF-beta on proteoglycan synthesis in equine articular cartilage.
Biochem Biophys Res Commun, 274(2), 467-471.
https://doi.org/10.1006/bbrc.2000.3167 Publication
Researcher Affiliations
- Department of Veterinary Basic Sciences and Farm Animal and Equine Medicine and Surgery, Royal Veterinary College, Royal College Street, London, NW1 0TU, United Kingdom. jiqbal@rvc.ac.uk
MeSH Terms
- Age Factors
- Aging / metabolism
- Animals
- Binding, Competitive
- Cartilage, Articular / drug effects
- Cartilage, Articular / metabolism
- Growth Substances / pharmacology
- Horses / embryology
- Horses / metabolism
- In Vitro Techniques
- Interleukin-1 / pharmacology
- Protein Isoforms / metabolism
- Protein Isoforms / pharmacology
- Proteoglycans / biosynthesis
- RNA, Messenger / biosynthesis
- Reference Values
- Reverse Transcriptase Polymerase Chain Reaction
- Sulfates / metabolism
- Sulfates / pharmacokinetics
- Sulfur Radioisotopes
- Transforming Growth Factor beta / genetics
- Transforming Growth Factor beta / metabolism
- Transforming Growth Factor beta / pharmacology
- Tretinoin / pharmacology
Citations
This article has been cited 17 times.- Gwam C, Ohanele C, Hamby J, Chughtai N, Mufti Z, Ma X. Human placental extract: a potential therapeutic in treating osteoarthritis. Ann Transl Med 2023 Jun 30;11(9):322.
- Thielen NGM, van der Kraan PM, van Caam APM. TGFβ/BMP Signaling Pathway in Cartilage Homeostasis. Cells 2019 Aug 24;8(9).
- Smit Y, Marais HJ, Thompson PN, Mahne AT, Goddard A. Clinical findings, synovial fluid cytology and growth factor concentrations after intra-articular use of a platelet-rich product in horses with osteoarthritis. J S Afr Vet Assoc 2019 May 23;90(0):e1-e9.
- Niemelä TM, Tulamo RM, Carmona JU, López C. Evaluation of the effect of experimentally induced cartilage defect and intra-articular hyaluronan on synovial fluid biomarkers in intercarpal joints of horses. Acta Vet Scand 2019 May 30;61(1):24.
- van der Kraan PM. The changing role of TGFβ in healthy, ageing and osteoarthritic joints. Nat Rev Rheumatol 2017 Mar;13(3):155-163.
- Chavez RD, Coricor G, Perez J, Seo HS, Serra R. SOX9 protein is stabilized by TGF-β and regulates PAPSS2 mRNA expression in chondrocytes. Osteoarthritis Cartilage 2017 Feb;25(2):332-340.
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- Peffers M, Liu X, Clegg P. Transcriptomic signatures in cartilage ageing. Arthritis Res Ther 2013 Aug 23;15(4):R98.
- Lotz M, Loeser RF. Effects of aging on articular cartilage homeostasis. Bone 2012 Aug;51(2):241-8.
- Loeser RF. Aging and osteoarthritis: the role of chondrocyte senescence and aging changes in the cartilage matrix. Osteoarthritis Cartilage 2009 Aug;17(8):971-9.
- Asanbaeva A, Masuda K, Thonar EJ, Klisch SM, Sah RL. Regulation of immature cartilage growth by IGF-I, TGF-beta1, BMP-7, and PDGF-AB: role of metabolic balance between fixed charge and collagen network. Biomech Model Mechanobiol 2008 Aug;7(4):263-76.
- Mitsuyama H, Healey RM, Terkeltaub RA, Coutts RD, Amiel D. Calcification of human articular knee cartilage is primarily an effect of aging rather than osteoarthritis. Osteoarthritis Cartilage 2007 May;15(5):559-65.
- Blaney Davidson EN, Vitters EL, van den Berg WB, van der Kraan PM. TGF beta-induced cartilage repair is maintained but fibrosis is blocked in the presence of Smad7. Arthritis Res Ther 2006;8(3):R65.
- 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(6):R1338-47.
- Tung JT, Fenton JI, Arnold C, Alexander L, Yuzbasiyan-Gurkan V, Venta PJ, Peters TL, Orth MW, Richardson DW, Caron JP. Recombinant equine interleukin-1beta induces putative mediators of articular cartilage degradation in equine chondrocytes. Can J Vet Res 2002 Jan;66(1):19-25.
- van der Kraan PM, van Caam APM, Blaney Davidson EN, van den Bosch MHJ, van de Loo FAJ. Growth factors that drive aggrecan synthesis in healthy articular cartilage. Role for transforming growth factor-β?. Osteoarthr Cartil Open 2024 Jun;6(2):100459.
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