In a recent study published in the Scientific Reports Journal, researchers examined the therapeutic potential of an injectable copolymer of stearic, palmitic, and oleic acids known as ARA 3,000 BETA for treating osteoarthritis.
Study: An injectable copolymer of fatty acids (ARA 3000 BETA) as a promising treatment for osteoarthritis. Image Credit: MDGRPHCS/Shutterstock.com
Background
Osteoarthritis is a chronic joint disease that affects the hips, knees, and fingers, and its prevalence is increasing with the aging population.
The bone sclerosis, cartilage degradation, synovial inflammation, calcification of the ligament and meniscus, and osteophyte formation characteristic of osteoarthritis causes severe joint pain leading to functional impairment.
The development and progression of osteoarthritis are linked to elevated levels of matrix metalloproteinases and pro-inflammatory cytokines.
Treatment options, such as non-steroid anti-inflammatory drugs and analgesics, are only symptomatic treatments to reduce pain and inflammation.
Due to their importance in cellular function maintenance and tissue homeostasis and their role in osteoarthritis and joint inflammation, dietary fatty acids have recently gained substantial interest.
Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been known to have anti-inflammatory properties and benefits for cartilage health and metabolism. Dietary n-3 PUFAs have shown an inverse relationship with the risk of osteoarthritis and synovitis.
Oleic and palmitic acids, which are forms of omega-9 monounsaturated fatty acids and saturated fatty acids, respectively, are two of the three most abundant fatty acids found in the synovial fluid of joints and have exhibited anti-inflammatory properties.
About the study
In the present study, the researchers used mice models of collagenase-induced osteoarthritis to evaluate the potential therapeutic properties of single and multiple doses of injectable ARA 3,000 BETA — a copolymer comprising stearic, palmitic, and oleic acids. The mice were divided into four groups, each consisting of 15 mice.
Group one was the control group, where the mice received an intra-articular injection of five µL saline in the right knee joints on the seventh day (osteoarthritic control) and in the left knee joints on day zero and the second day (healthy knee control).
The mice in the second group received two doses of 5 µL of ARA 3,000 BETA via intra-arterial injections to the right knee joint on the seventh day (intra-arterial group 1). The third group — intra-arterial group two — received the 5 µL of ARA 3,000 BETA intra-arterial injection to the right knee joint on the seventh and the 21st day.
The last group was the intra-muscular group, in which the mice were injected 50 µL of ARA 3,000 BETA through the Anterior tibialis muscle on the third, 11th, 18th, and 25th days.
On day 42, the mice were euthanized, and the hind paws were fixed in formaldehyde for analysis. A micro-computed tomography system was used to scan the hind paws and quantify the bone degradation in the epiphysis region of the tibial lateral and medial plateaus and the subchondral bone plate.
The calcification of the ligament and meniscus and the osteophyte formation in the knee joints were also quantified. Confocal laser scanning microscope images were used to quantitatively evaluate the thickness, surface degradation, and volume of the articular cartilage of the lateral and medial plateaus of the tibia.
The tibias were then decalcified and stained for the histological analysis of the bone and cartilage tissues.
Results
The results indicated that intra-arterial injections of ARA 3,000 BETA showed strong protective properties against cartilage degradations. The histological analysis of the knee joints showed protective effects after intra-arterial and intra-muscular injections of ARA 3,000 BETA.
The confocal laser scanning microscopy results also reported a significant improvement in the thickness, surface degradation, and volume of the articular cartilage of the tibial lateral and medial plateaus after the intra-arterial and intra-muscular injections of ARA 3,000 BETA.
The cartilage degradation was significantly reduced in the intra-arterially injected mice with a single dose of five µL of ARA 3,000 BETA.
The improvement in the cartilage parameters after four intra-muscular injections of 50 µL of ARA 3,000 BETA was slightly less significant compared to improvement after the intra-arterial injections, indicating that local injections of the fatty acid copolymer were more effective. However, while ARA 3,000 BETA exhibited protective effects against cartilage degradation, no regenerative properties were observed.
Slight protective effects were observed against the calcification of the knee joints and the bone parameters after the intra-muscular injections and, to a lesser degree, after two intra-arterial injections of the fatty acid copolymer.
Conclusions
Overall, the findings reported that injectable fatty acid copolymer ARA 3,000 BETA showed protective effects against cartilage degradation and improved cartilage parameters after intra-arterial and intra-muscular injections.
Slight improvements in bone parameters were also observed. The study highlights the therapeutic potential of fatty acid copolymers in treating osteoarthritis.
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