Statins and fibrates do not affect development of spontaneous cartilage damage in STR/Ort mice.
- Wei W Department of Orthopaedics, Erasmus MC University Medical Center, Rotterdam, The Netherlands. Electronic address: w.wei@erasmusmc.nl.
- Clockaerts S Department of Orthopaedics, Erasmus MC University Medical Center, Rotterdam, The Netherlands; Department of Orthopaedics, University of Antwerp, Antwerp, Belgium. Electronic address: stefan.clockaerts@ua.ac.be.
- Bastiaansen-Jenniskens YM Department of Orthopaedics, Erasmus MC University Medical Center, Rotterdam, The Netherlands. Electronic address: y.bastiaansen@erasmusmc.nl.
- Gierman LM TNO, Leiden, The Netherlands; Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: lobke.gierman@tno.nl.
- Botter SM Laboratory for Orthopedic Research, Department of Orthopedics, Balgrist University Hospital, Zurich, Switzerland. Electronic address: smbotter@hotmail.com.
- Bierma-Zeinstra SM Department of Orthopaedics, Erasmus MC University Medical Center, Rotterdam, The Netherlands; Department of General Practice, Erasmus MC University Medical Center, Rotterdam, The Netherlands. Electronic address: s.bierma-zeinstra@erasmusmc.nl.
- Weinans H Department of Orthopaedics, Erasmus MC University Medical Center, Rotterdam, The Netherlands; Department of Biomechanical Engineering, Delft University of Technology, Delft, The Netherlands; Department of Orthopaedics, Utrecht University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: h.weinans@erasmusmc.nl.
- Verhaar JA Department of Orthopaedics, Erasmus MC University Medical Center, Rotterdam, The Netherlands. Electronic address: j.verhaar@erasmusmc.nl.
- Kloppenburg M Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: g.kloppenburg@lumc.nl.
- Zuurmond AM TNO, Leiden, The Netherlands. Electronic address: anne-marie.zuurmond@tno.nl.
- van Osch GJ Department of Orthopaedics, Erasmus MC University Medical Center, Rotterdam, The Netherlands; Department of Otorhinolaryngology, Erasmus MC University Medical Center, Rotterdam, The Netherlands. Electronic address: g.vanosch@erasmusmc.nl.
- 2013-11-28
Published in:
- Osteoarthritis and cartilage. - 2014
Cartilage
Mouse
Osteoarthritis
Subchondral bone
Therapy pharmacological
Animals
Arthritis, Experimental
Biomarkers
Body Weight
Cartilage, Articular
Diet
Drug Evaluation, Preclinical
Drug Therapy, Combination
Fenofibrate
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Inflammation Mediators
Male
Mice
Mice, Inbred Strains
Osteoarthritis
Simvastatin
X-Ray Microtomography
English
OBJECTIVE
Since statins and fibrates are capable of improving the metabolic profile of patients as well as decreasing inflammation, they are considered as potential drugs for preventing osteoarthritis (OA). The goal of the present study was to investigate the effect of these drugs in the STR/Ort spontaneous OA mouse model.
DESIGN
Male STR/Ort mice received control diet or control diet containing two different dosages of simvastatin or fenofibrate or a combination of both. Mice were euthanized after 16 weeks of treatment at the age of 24 weeks. Serum analysis for metabolic and inflammatory markers, histologic OA grading and micro computed tomography (μCT) analysis of subchondral bone plate were performed.
RESULTS
Simvastatin treatment did not have a statistically significant effect on any of the measured parameters. Fenofibrate treated mice gained less body weight (BW) and had lower serum amyloid A (SAA) levels, but higher Interleukin (IL)-1α and MIP1α than other mice. Mice treated with 200 mg/kg BW/day fenofibrate had less subchondral bone plate volume than control, but no statistically significant reduction in cartilage damage. In the combination treatment group, BW and SAA were lower than control. Overall, bodyweight, synovium membrane cell layers and SAA levels correlated to subchondral bone plate changes and subchondral bone plate changes correlated to cartilage damage.
CONCLUSIONS
Statins and fibrates did not affect development of cartilage damage in the STR/Ort spontaneous OA mouse model. Fenofibrates however, had an effect on BW, serum inflammation markers and subchondral bone plate morphology.
Since statins and fibrates are capable of improving the metabolic profile of patients as well as decreasing inflammation, they are considered as potential drugs for preventing osteoarthritis (OA). The goal of the present study was to investigate the effect of these drugs in the STR/Ort spontaneous OA mouse model.
DESIGN
Male STR/Ort mice received control diet or control diet containing two different dosages of simvastatin or fenofibrate or a combination of both. Mice were euthanized after 16 weeks of treatment at the age of 24 weeks. Serum analysis for metabolic and inflammatory markers, histologic OA grading and micro computed tomography (μCT) analysis of subchondral bone plate were performed.
RESULTS
Simvastatin treatment did not have a statistically significant effect on any of the measured parameters. Fenofibrate treated mice gained less body weight (BW) and had lower serum amyloid A (SAA) levels, but higher Interleukin (IL)-1α and MIP1α than other mice. Mice treated with 200 mg/kg BW/day fenofibrate had less subchondral bone plate volume than control, but no statistically significant reduction in cartilage damage. In the combination treatment group, BW and SAA were lower than control. Overall, bodyweight, synovium membrane cell layers and SAA levels correlated to subchondral bone plate changes and subchondral bone plate changes correlated to cartilage damage.
CONCLUSIONS
Statins and fibrates did not affect development of cartilage damage in the STR/Ort spontaneous OA mouse model. Fenofibrates however, had an effect on BW, serum inflammation markers and subchondral bone plate morphology.
- Language
-
- English
- Open access status
- bronze
- Identifiers
-
- DOI 10.1016/j.joca.2013.11.009
- PMID 24280247
- Persistent URL
- https://folia.unifr.ch/global/documents/96528
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