Evidence for High Cholesterol to Contribute to Osteoarthritis

Researchers here report on a study in mice that suggests high blood cholesterol levels contribute to the progression of osteoarthritis, a degenerative condition of bone and cartilage in the joints. It is well known that high cholesterol is bad for health in a variety of other ways, and is one of the mechanisms linking conditions like obesity, metabolic syndrome, and diabetes to higher mortality rates. It speeds progression of atherosclerosis, for example, in which fatty deposits build up in blood vessels. The association with osteoarthritis is fairly new, however, and the researchers here suggest that mitochondrial dysfunction and oxidative stress are the mechanisms of interest in this relationship.

The contribution of metabolic factors on the severity of osteoarthritis (OA) is not fully appreciated. This study aimed to define the effects of hypercholesterolemia on the progression of OA. Apolipoprotein E-deficient (ApoE-/-) mice and diet-induced hypercholesterolemic (DIHC) rats were used to explore the effects of hypercholesterolemia on the progression of OA. Both models exhibited OA-like changes, characterized primarily by a loss of proteoglycans, collagen and aggrecan degradation, osteophyte formation, changes to subchondral bone architecture, and cartilage degradation. Surgical destabilization of the knees resulted in a dramatic increase of degradative OA symptoms in animals fed a high-cholesterol diet compared with controls. Clinically relevant doses of free cholesterol resulted in mitochondrial dysfunction, overproduction of reactive oxygen species (ROS), and increased expression of degenerative and hypertrophic markers in chondrocytes and breakdown of the cartilage extracellular matrix.

We showed that the severity of diet-induced OA changes could be attenuated by treatment with both atorvastatin and a mitochondrial targeting antioxidant. The protective effects of the mitochondrial targeting antioxidant were associated with suppression of oxidative damage to chondrocytes and restoration of extracellular matrix homeostasis of the articular chondrocytes. In summary, our data show that hypercholesterolemia precipitates OA progression by mitochondrial dysfunction in chondrocytes, in part by increasing ROS production and apoptosis. By addressing the mitochondrial dysfunction using antioxidants, we were able attenuate the OA progression in our animal models. This approach may form the basis for novel treatment options for this OA risk group in humans.

Link: http://dx.doi.org/10.1096/fj.201600600R

Comments

I appreciate all the info you provide. I request that you give a more precise definition of "high cholesterol levels." How high is too high?

Posted by: Renee Devereaux at November 16th, 2016 9:36 PM

@Renee Devereaux: You might look at the definitions of hypercholesterolemia, which include specific measurements.

Posted by: Reason at November 17th, 2016 6:56 AM

Dear Sir, it really most exist a strong link between cholesterol blood levels and severity of degenerative osteoarthritis. In my experience as clinician of more than 20 years I have been watching patients who modified high cholesterol diets to almost mediterranean diets and they redcuced their weight too. Bone pain, rigidity and cartilage destruction in main joints like hips and knees were strikingly reduce too. They could work better and they could live with less doscomfort.
Other patients paid expensively their unability to change thier way of eat and live. It is an interesting theme for all the people who want to increase their quality of life. Dr. Richard Sera from Mayabeque, Cuba.

Posted by: Richard Sera at March 27th, 2017 9:08 AM

I had high cholesterol for past 10 years and GP told me that I was fine even with strokes in family, also in these 10 years I have had osteoarthritis. Had a stroke in May this year, ever since being on statins pain caused by arthritis has practically disappeared, also I have been able to keep my weight down

Posted by: Manny Portelli at October 20th, 2021 10:15 PM
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