Chondrocyte apoptosis determined by caspase-3 expression varies with fibronectin distribution in equine articular cartilage.
Abstract: The purpose of this study was to investigate associations between the extent of chondrocyte apoptosis and expression of the articular cartilage (AC) extracellular matrix (ECM) molecules, cartilage oligomeric matrix protein (COMP) and fibronectin. Methods: Cartilage from four sites (when available) on equine left middle carpal joints (n = 12) were used. Expression of COMP and fibronectin was determined using specific polyclonal antibodies and a biotin-streptavidin/peroxidase method. The intensity of staining for matrix molecules was graded (none, mild, moderate, strong) in each cartilage zone. Apoptosis of chondrocytes in AC sections was assessed by their expression of active caspase-3 using immunohistochemistry. Results: The intensity of fibronectin expression varied significantly according to cartilage depth, with greater expression in the deep zone than in either the superficial or middle layers (P < 0.001). A significant positive association was found overall between intensity of fibronectin expression and chondrocyte apoptosis (r = 0.44, P = 0.0187). The data were also significant for superficial and deep zones (r = 0.44, P = 0.0239 and r = 0.42, P = 0.0279 respectively). Conversely, intensity of COMP expression did not show zonal differences and was un-associated with degree of apoptosis. However, COMP expression was significantly more intense in cartilage than fibronectin (P = 0.0007), and the correlation between overall intensity of COMP and fibronectin was statistically significant (r = 0.56, P = 0.0018). Conclusions: The positive correlation between the incidence of apoptosis and expression of fibronectin, a key ECM molecule involved in communication between the chondrocyte and surrounding matrix, suggests that chondrocyte death by apoptosis may alter cartilage metabolism, supporting the role of this process in the pathogenesis of osteoarthritis.
© 2011 The Authors. International Journal of Rheumatic Diseases © 2011 Asia Pacific League of Associations for Rheumatology and Blackwell Publishing Asia Pty Ltd.
Publication Date: 2011-07-21 PubMed ID: 21816026DOI: 10.1111/j.1756-185X.2011.01627.xGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This study explores the connection between chondrocyte cell death, or apoptosis, and the expression of molecules involved in the structure of articular cartilage in horses, specifically fibronectin and cartilage oligomeric matrix protein (COMP). The investigation revealed a strong association between fibronectin expression and apoptosis, hinting at potential implications in the development of osteoarthritis.
Objective and Methodology
- The research aimed to comprehend the relationship between chondrocyte apoptosis (cell death) and the expression of extracellular matrix (ECM) molecules in articular cartilage (AC), particularly COMP and fibronectin.
- Cartilage from different sites of equine left carpal joints were examined to ascertain the expression of COMP and fibronectin using specific antibodies and a method called biotin-streptavidin/peroxidase.
- They evaluated the staining intensity for ECM molecules as none, mild, moderate, or strong in each layer of the cartilage. Apoptosis was determined by analysing the expression of the active caspase-3 enzyme through immunohistochemistry, a technique used to detect specific proteins in cells of a tissue section.
Results
- The expression of fibronectin was distinctly different through the cartilage layers with the deepest zone showing the highest expression.
- There was a positive correlation between the intensity of fibronectin expression and chondrocyte apoptosis, implying these factors increase or decrease in tandem. This correlation was significant for the superficial and deep cartilage layers.
- On the other hand, COMP expression did not vary across cartilage zones, and it was not associated with apoptosis to any significant degree. COMP was found in greater concentration than fibronectin in the cartilage, and there was a significant correlation between the overall intensities of COMP and fibronectin.
Conclusion
- The significant association between chondrocyte apoptosis and fibronectin expression raises important questions about the function of these cellular events in the development of osteoarthritis. This highlights the need to further explore the role of fibronectin, a critical ECM molecule involved in intercellular communication, in the occurrence of chondrocyte cell death and potential implications on cartilage metabolism.
Cite This Article
APA
Thomas CM, Murray R, Sharif M.
(2011).
Chondrocyte apoptosis determined by caspase-3 expression varies with fibronectin distribution in equine articular cartilage.
Int J Rheum Dis, 14(3), 290-297.
https://doi.org/10.1111/j.1756-185X.2011.01627.x Publication
Researcher Affiliations
- Department of Anatomy, University of Bristol, Bristol, UK.
MeSH Terms
- Animals
- Apoptosis
- Cartilage, Articular / cytology
- Cartilage, Articular / metabolism
- Caspase 3 / metabolism
- Chondrocytes / enzymology
- Chondrocytes / pathology
- Extracellular Matrix Proteins / metabolism
- Female
- Fibronectins / metabolism
- Glycoproteins / metabolism
- Horses
- Matrilin Proteins
Grant Funding
- Biotechnology and Biological Sciences Research Council
Citations
This article has been cited 12 times.- Li G, Zhang M, Huang Y, Yang J, Dong L, Shi H, Li L, Liu R, Li J. The relationship between abnormal Core binding factor-β expression in human cartilage and osteoarthritis. BMC Musculoskelet Disord 2021 Feb 11;22(1):174.
- Zhuang C, Ni S, Yang ZC, Liu RP. Oxidative Stress Induces Chondrocyte Apoptosis through Caspase-Dependent and Caspase-Independent Mitochondrial Pathways and the Antioxidant Mechanism of Angelica Sinensis Polysaccharide. Oxid Med Cell Longev 2020;2020:3240820.
- Ma M, Liang X, Wang X, Zhang L, Cheng S, Guo X, Zhang F, Wen Y. The molecular mechanism study of COMP involved in the articular cartilage damage of Kashin-Beck disease. Bone Joint Res 2020 Sep;9(9):578-586.
- Musumeci G, Castrogiovanni P, Trovato FM, Weinberg AM, Al-Wasiyah MK, Alqahtani MH, Mobasheri A. Biomarkers of Chondrocyte Apoptosis and Autophagy in Osteoarthritis. Int J Mol Sci 2015 Aug 31;16(9):20560-75.
- Gao Y, Liu S, Huang J, Guo W, Chen J, Zhang L, Zhao B, Peng J, Wang A, Wang Y, Xu W, Lu S, Yuan M, Guo Q. The ECM-cell interaction of cartilage extracellular matrix on chondrocytes. Biomed Res Int 2014;2014:648459.
- Maldonado M, Nam J. The role of changes in extracellular matrix of cartilage in the presence of inflammation on the pathology of osteoarthritis. Biomed Res Int 2013;2013:284873.
- Zamli Z, Adams MA, Tarlton JF, Sharif M. Increased chondrocyte apoptosis is associated with progression of osteoarthritis in spontaneous Guinea pig models of the disease. Int J Mol Sci 2013 Aug 29;14(9):17729-43.
- Su S, Tian R, Jiao Y, Zheng S, Liang S, Liu T, Tian Z, Cao X, Xing Y, Ma C, Ni P, Yu F, Jiang T, Wang J. Ubiquitination and deubiquitination: Implications for the pathogenesis and treatment of osteoarthritis. J Orthop Translat 2024 Nov;49:156-166.
- Li J, Sun F, Zhang Y, Pan X, Li B, Zhang G, Zhou Q. MiR-103-3p regulates chondrocyte autophagy, apoptosis, and ECM degradation through the PI3K/Akt/mTOR pathway by targeting CPEB3. J Orthop Surg Res 2025 Mar 29;20(1):324.
- Raza IGA, Snelling SJB, Mimpen JY. Defining the extracellular matrix in non-cartilage soft-tissues in osteoarthritis: a systematic review. Bone Joint Res 2024 Dec 3;13(12):703-715.
- Cui L, Shen G, Yu Y, Yan Z, Zeng H, Ye X, Xu K, Zhu C, Li Y, Shen Z, Zhang B, Wu L. Gubi decoction mitigates knee osteoarthritis via promoting chondrocyte autophagy through METTL3-mediated ATG7 m(6)A methylation. J Cell Mol Med 2024 Aug;28(16):e70019.
- Lv H, Liu P, Hu H, Li X, Li P. MiR-98-5p plays suppressive effects on IL-1β-induced chondrocyte injury associated with osteoarthritis by targeting CASP3. J Orthop Surg Res 2024 Apr 13;19(1):239.
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