Chondrocyte Hypertrophy in Osteoarthritis: Mechanistic Studies and Models for the Identification of New Therapeutic Strategies
Articular cartilage shows limited self-healing ability owing to its low cellularity and avascularity. Untreated cartilage defects display an increased propensity to degenerate, leading to osteoarthritis (OA). During OA progression, articular chondrocytes are subjected to significant alterations in g...
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MDPI AG
2022-12-01
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| Online Access: | https://www.mdpi.com/2073-4409/11/24/4034 |
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| author | Shikha Chawla Andrea Mainardi Nilotpal Majumder Laura Dönges Bhupendra Kumar Paola Occhetta Ivan Martin Christian Egloff Sourabh Ghosh Amitabha Bandyopadhyay Andrea Barbero |
| author_facet | Shikha Chawla Andrea Mainardi Nilotpal Majumder Laura Dönges Bhupendra Kumar Paola Occhetta Ivan Martin Christian Egloff Sourabh Ghosh Amitabha Bandyopadhyay Andrea Barbero |
| author_sort | Shikha Chawla |
| collection | DOAJ |
| description | Articular cartilage shows limited self-healing ability owing to its low cellularity and avascularity. Untreated cartilage defects display an increased propensity to degenerate, leading to osteoarthritis (OA). During OA progression, articular chondrocytes are subjected to significant alterations in gene expression and phenotype, including a shift towards a hypertrophic-like state (with the expression of collagen type X, matrix metalloproteinases-13, and alkaline phosphatase) analogous to what eventuates during endochondral ossification. Present OA management strategies focus, however, exclusively on cartilage inflammation and degradation. A better understanding of the hypertrophic chondrocyte phenotype in OA might give new insights into its pathogenesis, suggesting potential disease-modifying therapeutic approaches. Recent developments in the field of cellular/molecular biology and tissue engineering proceeded in the direction of contrasting the onset of this hypertrophic phenotype, but knowledge gaps in the cause–effect of these processes are still present. In this review we will highlight the possible advantages and drawbacks of using this approach as a therapeutic strategy while focusing on the experimental models necessary for a better understanding of the phenomenon. Specifically, we will discuss in brief the cellular signaling pathways associated with the onset of a hypertrophic phenotype in chondrocytes during the progression of OA and will analyze in depth the advantages and disadvantages of various models that have been used to mimic it. Afterwards, we will present the strategies developed and proposed to impede chondrocyte hypertrophy and cartilage matrix mineralization/calcification. Finally, we will examine the future perspectives of OA therapeutic strategies. |
| first_indexed | 2024-03-09T17:13:36Z |
| format | Article |
| id | doaj.art-afdcda3596ba44ac93ea0be1d15ac19a |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T17:13:36Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-afdcda3596ba44ac93ea0be1d15ac19a2023-11-24T13:54:40ZengMDPI AGCells2073-44092022-12-011124403410.3390/cells11244034Chondrocyte Hypertrophy in Osteoarthritis: Mechanistic Studies and Models for the Identification of New Therapeutic StrategiesShikha Chawla0Andrea Mainardi1Nilotpal Majumder2Laura Dönges3Bhupendra Kumar4Paola Occhetta5Ivan Martin6Christian Egloff7Sourabh Ghosh8Amitabha Bandyopadhyay9Andrea Barbero10Department of Surgery, Faculty of Medicine and Health Sciences, Research Institute of the McGill University Health Centre, Montreal, QC H3G 1A4, CanadaDepartment of Biomedicine, University Hospital Basel, University of Basel, 4031 Basel, SwitzerlandRegenerative Engineering Laboratory, Department of Textile and Fibre Engineering, Indian Institute of Technology Delhi, Delhi 110016, IndiaDepartment of Biomedicine, University Hospital Basel, University of Basel, 4031 Basel, SwitzerlandDepartment of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur 208016, Uttar Pradesh, IndiaDepartment of Electronics, Information and Bioengineering, Politecnico di Milano, 20133 Milano, ItalyDepartment of Biomedicine, University Hospital Basel, University of Basel, 4031 Basel, SwitzerlandDepartment of Orthopaedic Surgery and Traumatology, University Hospital Basel, 4031 Basel, SwitzerlandRegenerative Engineering Laboratory, Department of Textile and Fibre Engineering, Indian Institute of Technology Delhi, Delhi 110016, IndiaDepartment of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur 208016, Uttar Pradesh, IndiaDepartment of Biomedicine, University Hospital Basel, University of Basel, 4031 Basel, SwitzerlandArticular cartilage shows limited self-healing ability owing to its low cellularity and avascularity. Untreated cartilage defects display an increased propensity to degenerate, leading to osteoarthritis (OA). During OA progression, articular chondrocytes are subjected to significant alterations in gene expression and phenotype, including a shift towards a hypertrophic-like state (with the expression of collagen type X, matrix metalloproteinases-13, and alkaline phosphatase) analogous to what eventuates during endochondral ossification. Present OA management strategies focus, however, exclusively on cartilage inflammation and degradation. A better understanding of the hypertrophic chondrocyte phenotype in OA might give new insights into its pathogenesis, suggesting potential disease-modifying therapeutic approaches. Recent developments in the field of cellular/molecular biology and tissue engineering proceeded in the direction of contrasting the onset of this hypertrophic phenotype, but knowledge gaps in the cause–effect of these processes are still present. In this review we will highlight the possible advantages and drawbacks of using this approach as a therapeutic strategy while focusing on the experimental models necessary for a better understanding of the phenomenon. Specifically, we will discuss in brief the cellular signaling pathways associated with the onset of a hypertrophic phenotype in chondrocytes during the progression of OA and will analyze in depth the advantages and disadvantages of various models that have been used to mimic it. Afterwards, we will present the strategies developed and proposed to impede chondrocyte hypertrophy and cartilage matrix mineralization/calcification. Finally, we will examine the future perspectives of OA therapeutic strategies.https://www.mdpi.com/2073-4409/11/24/4034osteoarthritiscartilagehypertrophysignaling pathway |
| spellingShingle | Shikha Chawla Andrea Mainardi Nilotpal Majumder Laura Dönges Bhupendra Kumar Paola Occhetta Ivan Martin Christian Egloff Sourabh Ghosh Amitabha Bandyopadhyay Andrea Barbero Chondrocyte Hypertrophy in Osteoarthritis: Mechanistic Studies and Models for the Identification of New Therapeutic Strategies Cells osteoarthritis cartilage hypertrophy signaling pathway |
| title | Chondrocyte Hypertrophy in Osteoarthritis: Mechanistic Studies and Models for the Identification of New Therapeutic Strategies |
| title_full | Chondrocyte Hypertrophy in Osteoarthritis: Mechanistic Studies and Models for the Identification of New Therapeutic Strategies |
| title_fullStr | Chondrocyte Hypertrophy in Osteoarthritis: Mechanistic Studies and Models for the Identification of New Therapeutic Strategies |
| title_full_unstemmed | Chondrocyte Hypertrophy in Osteoarthritis: Mechanistic Studies and Models for the Identification of New Therapeutic Strategies |
| title_short | Chondrocyte Hypertrophy in Osteoarthritis: Mechanistic Studies and Models for the Identification of New Therapeutic Strategies |
| title_sort | chondrocyte hypertrophy in osteoarthritis mechanistic studies and models for the identification of new therapeutic strategies |
| topic | osteoarthritis cartilage hypertrophy signaling pathway |
| url | https://www.mdpi.com/2073-4409/11/24/4034 |
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