Chondrocytes harvested from osteochondritis dissecans cartilage are able to undergo limited in vitro chondrogenesis despite having perturbations of cell phenotype in vivo.
Abstract: Our objective was to characterize the variation in gene expression for key genes associated with chondrogenic phenotype of osteochondrosis (OC)-affected and normal chondrocytes, and to identify whether OC chondrocytes can redifferentiate and regain a phenotype similar to normal chondrocytes if appropriate chondrogenic signals are given. Equine articular cartilage removed at surgery to treat clinically significant OC lesions was collected (n = 10), and the gene expression evaluated and compared to aged-matched normal samples (n = 10). Cartilage was harvested from normal (n = 4) and OC (n = 3) joints from horses at necropsy. Chondrogenic pellet cultures were established following monolayer proliferation. After 14 days in culture, the pellets were assessed by histochemical and pellet weight analysis, assay of glycosaminoglycan (GAG) content, and gene expression. Chondrocytes from OC cartilage expressed significantly more Coll-I, -II, -III, and -X than chondrocytes from normal cartilage (all p < 0.0001). Furthermore, OC chondrocytes expressed significantly more MMP-13, ADAMTS-4 (both p < 0.0001), and TIMP-1 (p < 0.001) and significantly less TIMP-2 and TIMP-3. Pellets created from OC chondrocytes contained significantly less GAG (p = 0.0069) and expressed significantly less Sox9 and significantly more superficial zone protein (SZP) (p = 0.0105) than pellets created from normal cartilage. The results suggest that chondrocytes from OC cartilage at the time of surgical treatment have perturbations in phenotype compared to cells from normal cartilage. Despite these differences, following monolayer expansion and pellet culture under chondrogenic conditions, chondrocytes derived from OC cartilage retain some ability to undergo chondrogenic differentiation and synthesize an appropriate cartilage-like matrix. However, this chondrogenic differentiation potential is inferior to that seen in aged-matched normal chondrocytes.
Publication Date: 2008-03-11 PubMed ID: 18327793DOI: 10.1002/jor.20602Google Scholar: Lookup
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- Journal Article
Summary
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The research explored the variation of gene expression in chondrocytes from osteochondritis dissecans (OC) cartilage, compared to normal chondrocytes. The study found that, despite irregularities in phenotype, chondrocytes from OC cartilage show limited capability for chondrogenic differentiation and synthesis of cartilage-like matrix in vitro.
Objective and Methodology
- The study aimed to examine the variations in gene expression for certain key genes tied to the chondrogenic phenotype of OC-affected and standard chondrocytes.
- The researchers collected articular cartilage from horses treated surgically for OC lesions.
- The cartilage collected was compared to aged-matched normal samples to investigate any irregularities or changes in gene expression.
- Chondrogenic pellet cultures were established post-mono layer proliferation.
Results and Analysis
- The researchers found that chondrocytes from OC cartilage significantly expressed more types of collagen genes (Coll-I, -II, -III, and -X) than normal cartilage.
- OC chondrocytes also expressed more MMP-13, ADAMTS-4, and TIMP-1, but less TIMP-2 and TIMP-3 compared to regular chondrocytes.
- The pellets created from OC chondrocytes maintained significantly lower levels of glycosaminoglycan (GAG) and higher expressions of superficial zone protein (SZP) and less Sox9.
Conclusion
- The findings suggest that at the time of surgical treatment, chondrocytes from OC cartilage display phenotype perturbations compared to cells from normal cartilage.
- Despite these phenotype variations, chondrocytes derived from OC cartilage retain some ability to undergo chondrogenic differentiation under specific conditions and can produce an appropriate cartilage-like matrix.
- However, this chondrogenic differentiation potential is less compared to age-matched normal chondrocytes.
Cite This Article
APA
Garvican ER, Vaughan-Thomas A, Redmond C, Clegg PD.
(2008).
Chondrocytes harvested from osteochondritis dissecans cartilage are able to undergo limited in vitro chondrogenesis despite having perturbations of cell phenotype in vivo.
J Orthop Res, 26(8), 1133-1140.
https://doi.org/10.1002/jor.20602 Publication
Researcher Affiliations
- Musculoskeletal Research Group, The University of Liverpool Veterinary Teaching Hospital, Leahurst, Neston, Wirral, United Kingdom. e.garvican@knac.com
MeSH Terms
- Animals
- Cartilage / cytology
- Cartilage / physiology
- Cell Differentiation / physiology
- Cells, Cultured
- Chondrocytes / pathology
- Chondrocytes / physiology
- Chondrogenesis / physiology
- Collagen / genetics
- Extracellular Matrix Proteins / genetics
- Gene Expression / physiology
- Horse Diseases / pathology
- Horse Diseases / physiopathology
- Horses
- In Vitro Techniques
- Matrix Metalloproteinases / genetics
- Osteoarthritis / pathology
- Osteoarthritis / physiopathology
- Osteoarthritis / veterinary
- Osteochondritis Dissecans / pathology
- Osteochondritis Dissecans / physiopathology
- Osteochondritis Dissecans / veterinary
- Phenotype
- Signal Transduction / physiology
- Tissue Inhibitor of Metalloproteinases / genetics
Citations
This article has been cited 8 times.- Vapniarsky N, Moncada L, Garrity C, Wong A, Filliquist B, Chou PY, Kapatkin AS, Marcellin-Little DJ. Tissue Engineering of Canine Cartilage from Surgically Debrided Osteochondritis Dissecans Fragments. Ann Biomed Eng 2022 Jan;50(1):56-77.
- Arévalo-Turrubiarte M, Baratta M, Ponti G, Chiaradia E, Martignani E. Extracellular vesicles from equine mesenchymal stem cells decrease inflammation markers in chondrocytes in vitro. Equine Vet J 2022 Nov;54(6):1133-1143.
- Paatela T, Vasara A, Sormaala M, Nurmi H, Kautiainen H, Kiviranta I. Chondral and Osteochondritis Dissecans Lesions Treated by Autologous Chondrocytes Implantation: A Mid- to Long-Term Nonrandomized Comparison. Cartilage 2021 Dec;13(1_suppl):1105S-1112S.
- Chiaradia E, Pepe M, Orvietani PL, Renzone G, Magini A, Sforna M, Emiliani C, Di Meo A, Scaloni A. Proteome Alterations in Equine Osteochondrotic Chondrocytes. Int J Mol Sci 2019 Dec 7;20(24).
- Kornicka K, Al Naem M, Röcken M, Zmiertka M, Marycz K. Osteochondritis Dissecans (OCD)-Derived Chondrocytes Display Increased Senescence, Oxidative Stress, Chaperone-Mediated Autophagy and, in Co-Culture with Adipose-Derived Stem Cells (ASCs), Enhanced Expression of MMP-13. J Clin Med 2019 Mar 8;8(3).
- Grier WK, Iyoha EM, Harley BAC. The influence of pore size and stiffness on tenocyte bioactivity and transcriptomic stability in collagen-GAG scaffolds. J Mech Behav Biomed Mater 2017 Jan;65:295-305.
- Sakata K, Furumatsu T, Miyazawa S, Okada Y, Fujii M, Ozaki T. Comparison between normal and loose fragment chondrocytes in proliferation and redifferentiation potential. Int Orthop 2013 Jan;37(1):159-65.
- Caliari SR, Weisgerber DW, Ramirez MA, Kelkhoff DO, Harley BA. The influence of collagen-glycosaminoglycan scaffold relative density and microstructural anisotropy on tenocyte bioactivity and transcriptomic stability. J Mech Behav Biomed Mater 2012 Jul;11:27-40.
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