Ascorbic Acid Attenuates Senescence of Human Osteoarthritic Osteoblasts
Open accessAbstract
The accumulation of senescent cells is implicated in the pathology of several age-related diseases. While the clearance of senescent cells has been suggested as a therapeutic target for patients with osteoarthritis (OA), cellular senescence of bone-resident osteoblasts (OB) remains poorly explored. Since oxidative stress is a well-known inducer of cellular senescence, we here investigated the effect of antioxidant supplementation on the isolation efficiency, expansion, differentiation potential, and transcriptomic profile of OB from osteoarthritic subchondral bone. Bone chips were harvested from sclerotic and non-sclerotic regions of the subchondral bone of human OA joints. The application of 0.1 mM ascorbic acid-2-phosphate (AA) significantly increased the number of outgrowing cells and their proliferation capacity. This enhanced proliferative capacity showed a negative correlation with the amount of senescent cells and was accompanied by decreased expression of reactive oxygen species (ROS) in cultured OB. Expanded cells continued to express differentiated OB markers independently of AA supplementation and demonstrated no changes in their capacity to osteogenically differentiate. Transcriptomic analyses revealed that apoptotic, cell cycle–proliferation, and catabolic pathways were the main pathways affected in the presence of AA during OB expansion. Supplementation with AA can thus help to expand subchondral bone OB in vitro while maintaining their special cellular characteristics. The clearance of such senescent OB could be envisioned as a potential therapeutic target for the treatment of OA.
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Ascorbic acid has a protective effect on human chondrocytes against OS by attenuating the increase of apoptosis, the loss of viability and the increase of senescence, and therefore hindering the development of osteoarthritis and aging of cartilage.
“Moreover, AA was found to have a protective effect also on human chondrocytes against OS by attenuating the increase of apoptosis, the loss of viability and the increase of senescence, and therefore hindering the development of osteoarthritis and aging of cartilage [125,126].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [126]
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The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence
Varesi, A., Chirumbolo, S., Campagnoli, L. I. M., Pierella, E., Piccini, G. B., Carrara, A., Ricevuti, G., Scassellati, C., Bonvicini, C., & Pascale, A. (2022) · Antioxidants · doi:10.3390/antiox11071224 · Cited by 145 · see citing works
- Authors
- Burger, M., Steinitz, A., Geurts, J., Pippenger, B., Schaefer, D., Martin, I., Barbero, A., & Pelttari, K.
- Affiliations
- University of Basel (CH)
- Department of Biomedicine, University of Basel, University Hospital of Basel, 4031 Basel, Switzerland
- Corresponding author
- Barbero, Andrea
- ORCID
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2017-11-24
- Volume
- 18
- Issue
- 12
- Pages
- 2517
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC5751120
- OpenAlex
- W2769108240
- Cited by
- 25
- References
- 74
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 7 · 2022: 4 · 2021: 3 · 2019: 3 · 2018: 4
- FWCI
- 1.42
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (310030_149614)
- Gottfried & Julia Bangerter-Rhyner Foundation
- Department of Surgery, University Hospital of Basel
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Keywords
- vitamin C, cellular senescence, osteoblasts, osteoarthritis, subchondral bone, oxidative stress, reactive oxygen species, antioxidant supplementation, osteogenic differentiation, gene expression profiling, senolytic therapy
- MeSH terms
- Adult, Aged, Aged, 80 and over, Antioxidants, Ascorbic Acid, Cells, Cultured, Female, Humans, Male, Middle Aged, Osteoarthritis, Osteoblasts, Vitamins, Cellular Senescence, Reactive Oxygen Species, Cell Proliferation, Transcriptome
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