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Updated: Aug 29, 2026
Real-time Visualization and Analysis of Chondrocyte Injury Due to Mechanical Loading in Fully Intact Murine Cartilage Explants
Published on: January 7, 2019
Chondrocyte death during murine osteoarthritis
D Mistry1, Y Oue, M G Chambers
1Department of Experimental Biology, William Harvey Research Institute, St. Bartholomew's and The Royal London School of Medicine and Dentistry, Charterhouse Square, EC1M 6BQ, London, UK.
Objective:
To determine whether chondrocyte apoptosis occurs during the progression of osteoarthritis (OA) in the STR/ort mouse model of OA.
Methods:
Serial cryostat sections were cut (10 microns) through the knee joint of young and old male STR/ort mice and graded for the severity of OA lesions. Age- and sex-matched CBA mice were used as controls. Apoptotic chondrocytes were detected using the TUNEL assay. Ultrastructural changes were examined using electron microscopy (EM). Expression of biochemical markers associated with apoptosis (bax, bcl-2 and caspases-3, -8 & -9) was investigated using immunohistochemistry.
Results:
TUNEL assays on histological sections of STR/ort knee joints showed that the number of TUNEL-positive chondrocytes in the tibial medial articular cartilage correlated with the severity of the OA damage. These cells were located close to the lesional area. Only very occasional TUNEL positive chondrocytes were detected in either morphologically normal STR/ort cartilage or in control CBA cartilage. Ultrastructural analysis of chondrocytes neighboring focal osteoarthritic lesions in STR/ort tibial cartilage revealed an abundance of abnormal cells exhibiting numerous morphological changes. These resembled, but in some cases differed, from changes reported in classical apoptosis. The changes include abnormal distribution of chromatin, cell shrinkage, membrane blebbing and deposition of cell remnants (apoptotic bodies) in the lacuna space. Despite the TUNEL and EM changes, immunohistochemistry failed to detect any changes in the ratio of bax to bcl-2 in tibial chondrocytes of STR/ort mice. Both bcl-2 and bax levels decreased with age in morphologically normal STR/ort and control CBA cartilage. None of the caspases tested for was detected in tibial chondrocytes of either strain.
Conclusion:
Chondrocyte cell death is correlated with the progression of OA in STR/ort mice and has many of the morphological characteristics of classical apoptosis. Absence of changes in bax to bcl-2 ratio in STR/ort chondrocytes indicate that the mitochondrial pathway of apoptosis is unlikely to be involved. Failure to detect caspases could be due to low levels of enzyme expression, expression within a very brief time period, or to a caspase-independent mechanism of cell death.
Insights
Chondrocyte apoptosis, a form of cell death, is linked to osteoarthritis (OA) progression in STR/ort mice. This cell death exhibits apoptotic features but may not involve the mitochondrial pathway or caspases.
Area of Science:
- Biomedical Science
- Cell Biology
- Orthopedics
Background:
- Osteoarthritis (OA) is a degenerative joint disease.
- The role of chondrocyte apoptosis in OA pathogenesis is not fully understood.
Purpose of the Study:
- To investigate chondrocyte apoptosis during OA progression in the STR/ort mouse model.
- To characterize the morphological and molecular features of chondrocyte cell death in OA.
Main Methods:
- TUNEL assay and electron microscopy (EM) were used to detect and examine apoptotic chondrocytes in STR/ort mice.
- Immunohistochemistry was employed to assess the expression of apoptosis-related markers (bax, bcl-2, caspases).
Main Results:
- TUNEL-positive chondrocytes increased with OA severity in STR/ort mice, primarily near lesions.
- EM revealed chondrocytes with apoptotic morphology, including chromatin condensation and blebbing.
- No changes in bax/bcl-2 ratio were observed, and caspases were not detected in STR/ort chondrocytes.
Conclusions:
- Chondrocyte cell death in OA progression in STR/ort mice shares morphological traits with apoptosis.
- The mitochondrial pathway and caspases may not be the primary mechanisms driving this cell death in this model.
