Related Experiment Video
Updated: Jan 12, 2026
Ameliorating Osteoarthritis in Mice Using Silver Nanoparticles
Published on: June 2, 2023
β-galactosidase-targeted senolytic prodrug ameliorates preclinical models of post-traumatic osteoarthritis
1Department of Sports Medicine, Institute of Sports Medicine of Peking University, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, China; Centre of Foot and Ankle Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Background:
Cellular senescence is involved in the pathogenesis of osteoarthritis (OA). This study aimed to identify prodrug SSK1 as a senolytic strategy for alleviating OA.
Methods:
An oxidative stress-induced cellular senescence model was established to evaluate cell viability, replication, and genotoxicity after SSK1 treatment. Human OA chondrocytes and explants were collected to evaluate the therapeutic effect of prodrug SSK1 in vitro. In vivo evaluation was performed in young and aged male murine models. SSK1 (intra-articular injection every 3 days) was administrated 2 weeks after anterior cruciate ligament transection (ACLT) surgery. Animals were sacrificed 8 weeks after surgery. OA phenotype was analysed by micro-computerised tomography (μCT), histology and pain-related behaviour tests.
Findings:
SSK1 showed precise, efficient, and broad-spectrum elimination of senescent chondrocytes. When co-cultured with human osteoarthritic chondrocytes and cartilage explants, the senolytic SSK1 prevented the generation of senescence-associated secretory phenotype factors, enhanced production of extracellular matrix (ECM) molecules, and promoted a regenerative chondral environment. Intra-articular administration of SSK1 showed improved pain response, enhanced retention of ECM, and remodelled subchondral bone homeostasis in both young and aged ACLT-induced OA murine model.
Interpretation:
SSK1 is an effective candidate for senolytics in alleviating OA. The anti-ageing therapeutic effect of SSK1 lies in restoring a regenerative phenotype by improving the proliferation microenvironment, and reducing the accumulation of apoptotic signals in the joint microenvironment.
Funding:
Funded by the Regional Innovation Joint Fund of the National Natural Science Foundation of China (Integrated Project) (U23A6009), the National Natural Science Foundation of China (82202687, 82172420, and 82072486), the Beijing Municipal Natural Science Foundation (7222213), and the Capital's Funds for Health Improvement and Research (2022-4-20511), and Beijing Tongren Hospital Seed Funds (2021-YJJ-ZZL-008).
Insights
Prodrug SSK1 effectively eliminates senescent cells, offering a promising senolytic strategy for osteoarthritis (OA). This innovative treatment alleviates OA symptoms by restoring a regenerative joint environment and improving cartilage health.
Area of Science:
- Biomedical Science
- Regenerative Medicine
- Osteoarthritis Research
Background:
- Cellular senescence contributes to osteoarthritis (OA) pathogenesis.
- Identifying senolytic agents is crucial for OA treatment.
Purpose of the Study:
- To evaluate prodrug SSK1 as a senolytic strategy for OA.
- To assess SSK1's efficacy in preclinical OA models.
Main Methods:
- Established an oxidative stress-induced cellular senescence model.
- Tested SSK1 in human OA chondrocytes, explants, and murine OA models (ACLT-induced).
- Analyzed OA phenotype using μCT, histology, and behavioral tests.
Main Results:
- SSK1 precisely eliminated senescent chondrocytes.
- SSK1 prevented senescence-associated secretory phenotype factors and enhanced extracellular matrix (ECM) production.
- SSK1 improved pain response, ECM retention, and subchondral bone homeostasis in OA models.
Conclusions:
- SSK1 is an effective senolytic candidate for OA.
- SSK1 restores a regenerative phenotype by improving the joint microenvironment.
- SSK1 reduces apoptotic signals, promoting joint health.
