The role of chondrocyte senescence in osteoarthritis
Open accessAbstract
Summary: Replicative senescence occurs when normal somatic cells stop dividing. Senescent cells remain viable, but show alterations in phenotype, e.g. altered expression of matrix metalloproteinases ( MMPs ); these enzymes are known to be involved in cartilage destruction. It is assumed that cells deplete their replicative potential during aging, and age is a major risk factor for osteoarthritis (OA). Therefore, we hypothesized that chondrocytes in aging or diseased cartilage become senescent with associated phenotypic changes contributing to development or progression of OA. Articular cartilage was obtained from OA patients undergoing arthroplasty, with ‘normal’ cartilage from trauma surgery for hip fracture. Senescent cells were identified using the senescence‐associated β‐galactosidase (SA‐β‐gal) marker. Telomere length was assessed using Southern blot. MMP expression was measured at the mRNA level using Taqman® RT‐PCR. No SA‐β‐gal staining was observed in control cartilage regardless of patient age. In contrast, SA‐β‐gal staining was observed in damaged OA cartilage adjacent to the lesion. Cultured chondrocytes isolated from sites near a lesion contained a greater percentage of SA‐β‐gal positive cells than cultures isolated from distal sites or normal cartilage. Mean telomere length was shorter in cells near the lesion compared to distal sites in the same joint; thus the former population has undergone cell division. The expression of collagenases MMP‐1 , ‐8 and ‐13 and tissue inhibitor of metalloproteinases (TIMP)‐1 was altered in OA cartilage, but no difference was detected between lesion and distal sites in the same joint (i.e. no correlation was found between senescent cells and proteinase/inhibitor expression).
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Senescent cells have been found at sites of age-related pathologies such as osteoarthritis and atherosclerosis.
“and have been found at sites of age-related pathologies such as osteoarthritis and atherosclerosis [ 28 – 30 ].”
From Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor (2008) · cites this paper as [28]
The Discussion reports senescent cells close to osteoarthritic lesions in hip and knee cartilage. The Introduction reports senescence-marker use in arteries and suggests that endothelial senescence may contribute to atherosclerosis, but it does not clearly state that senescent cells were found at atherosclerotic lesions. (LLM, conf=0.82)
Experimental — accuracy not yet measuredCultured chondrocytes near hip osteoarthritis lesions have shorter mean telomere length and more senescence markers than chondrocytes from distal sites in the same joint.
“cultured chondrocytes isolated from areas close to the osteoarthritis lesions from the hips of patients have shorter mean telomere length and increased levels of senescence markers than those from distal sites in the same joint126”
From Telomere dysfunction in ageing and age-related diseases (2022) · cites this paper as [126]
The role of senescent chondrocytes in osteoarthritis pathogenesis is unknown.
“yet their role in disease pathogenesis is unknown.”
From Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment (2017) · cites this paper as [12]
Senescent chondrocytes are found in cartilage tissue isolated from patients undergoing joint replacement surgery.
“Senescent chondrocytes are found in cartilage tissue isolated from patients undergoing joint replacement surgery11–14”
From Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment (2017) · cites this paper as [12]
Articular cartilage of patients with osteoarthritis shows features of senescence, including increased nitric oxide and pro-inflammatory cytokines, p16, activated DNA damage response, ROS secretion and SA-β-Gal activity.
“Articular cartilage of patients with OA shows features of senescence, including increased expression of nitric oxide, pro-inflammatory cytokines, particularly IL-1β [8]; p16 [9]; activated DNA damage response; ROS secretion and SA-β-Gal activity [10].”
From Fibrates as drugs with senolytic and autophagic activity for osteoarthritis therapy (2019) · cites this paper as [10]
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- Authors
- Price, J. S., Waters, J. G., Darrah, C., Pennington, C., Edwards, D. R., Donell, S. T., & Clark, I. M.
- Affiliations
- University of East Anglia (GB)
- Norfolk and Norwich University Hospital (GB)
- Corresponding author
- Clark, Ian M.
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2002-09-15
- Volume
- 1
- Issue
- 1
- Pages
- 57-65
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- OpenAlex
- W2032691826
- Cited by
- 386
- References
- 31
- Citations by year
- 2026: 14 · 2025: 22 · 2024: 32 · 2023: 23 · 2022: 25 · 2021: 16 · 2020: 31 · 2019: 30 · 2018: 16 · 2017: 24 · 2016: 12 · 2015: 18 · 2014: 12 · 2013: 14 · 2012: 15
- FWCI
- 2.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Aging Cell (publishedVersion)
- PubMed (publishedVersion)
- UEA Digital Repository (University of East Anglia) (submittedVersion)
- Funders
- Lawrence Berkeley National Laboratory
- Topics
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Surgery › Hip disorders and treatments
- Keywords
- chondrocyte senescence, osteoarthritis, replicative senescence, senescence-associated β-galactosidase, telomere length, matrix metalloproteinases, collagenase, MMP-1, MMP-8, MMP-13, TIMP-1, articular cartilage, cartilage destruction, aging
- MeSH terms
- Aged, Aged, 80 and over, beta-Galactosidase, Cartilage, Articular, Cells, Cultured, Humans, Middle Aged, Osteoarthritis, RNA, Messenger, Biomarkers, Telomere, Cellular Senescence, Tissue Inhibitor of Metalloproteinase-1, Chondrocytes, Matrix Metalloproteinases
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