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Updated: Nov 12, 2025
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
Novel high-intensive cholesterol-lowering therapies do not ameliorate knee OA development in humanized dyslipidemic
Y van Gemert1, A E Kozijn2, M G Pouwer3
1Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands.
Objective:
High systemic cholesterol levels have been associated with osteoarthritis (OA) development. Therefore, cholesterol lowering by statins has been suggested as a potential treatment for OA. We investigated whether therapeutic high-intensive cholesterol-lowering attenuated OA development in dyslipidemic APOE∗3Leiden.CETP mice.
Methods:
Female mice (n = 13-16 per group) were fed a Western-type diet (WTD) for 38 weeks. After 13 weeks, mice were divided into a baseline group and five groups receiving WTD alone or with treatment: atorvastatin alone, combined with PCSK9 inhibitor alirocumab and/or ANGPTL3 inhibitor evinacumab. Knee joints were analysed for cartilage degradation, synovial inflammation and ectopic bone formation using histology. Aggrecanase activity in articular cartilage and synovial S100A8 expression were determined as markers of cartilage degradation/regeneration and inflammation.
Results:
Cartilage degradation and active repair were significantly increased in WTD-fed mice, but cholesterol-lowering strategies did not ameliorate cartilage destruction. This was supported by comparable aggrecanase activity and S100A8 expression in all treatment groups. Ectopic bone formation was comparable between groups and independent of cholesterol levels.
Conclusions:
Intensive therapeutic cholesterol lowering per se did not attenuate progression of cartilage degradation in dyslipidemic APOE∗3Leiden.CETP mice, with minor joint inflammation. We propose that inflammation is a key feature in the disease and therapeutic cholesterol-lowering strategies may still be promising for OA patients presenting both dyslipidemia and inflammation.
Insights
High cholesterol is linked to osteoarthritis (OA). This study found that intensive cholesterol-lowering treatments did not prevent cartilage damage in mice with high cholesterol, suggesting inflammation is key for OA progression.
Area of Science:
- Biomedical research
- Osteoarthritis research
- Cardiovascular research
Background:
- Systemic high cholesterol levels are associated with osteoarthritis (OA) development.
- Cholesterol-lowering statins are being explored as a potential OA treatment.
Purpose of the Study:
- To investigate if intensive cholesterol-lowering therapy can reduce OA progression in dyslipidemic mice (APOE*3Leiden.CETP).
Main Methods:
- Female mice were fed a Western-type diet for 38 weeks.
- Treatments included atorvastatin, PCSK9 inhibitor alirocumab, and ANGPTL3 inhibitor evinacumab.
- Knee joints were analyzed for cartilage degradation, inflammation, and bone formation.
Main Results:
- While cartilage degradation and repair increased in mice on a Western diet, cholesterol-lowering strategies did not improve cartilage destruction.
- Aggrecanase activity and S100A8 expression were similar across all treatment groups.
- Ectopic bone formation was comparable and not dependent on cholesterol levels.
Conclusions:
- Intensive cholesterol lowering alone did not attenuate cartilage degradation in dyslipidemic mice, despite minor joint inflammation.
- Inflammation appears to be a critical factor in OA progression.
- Cholesterol-lowering therapies may still benefit OA patients with co-existing dyslipidemia and inflammation.
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