NRF2 as potential treatment target for osteoarthritis


Osteoarthritis is common in older adults, but there are no treatments for the root causes of the disease. Marchev and colleagues review recent research that points to NRF2 as a potential target for treatment of osteoarthritis.

Osteoarthritis is a condition in which the joints of the body degenerate. Many older adults experience osteoarthritis, which can lead to pain, deformity, and disability. Currently, there is no cure for osteoarthritis, and patients often need complete joint replacements as their last recourse of treatment. Osteoarthritis occurs due to an imbalance between bone formation and bone resorption—cartilage is damaged, bone is resorbed, and bone-building cells overcompensate by building too much new bone. This imbalance is linked to inflammation and oxidation of the joint cartilages, which in turn worsen the condition. NRF2 is a protein that counters these processes.

In the Annals of the New York Academy of Sciences, Marchev and colleagues reviewed the available information about the role of inflammation, oxidation, and NRF2 in shaping osteoarthritis.Recent research has shown that immune system cells called neutrophils can induce inflammatory responses that elicit greater bone damage—these cells are found in the joints of mice with osteoarthritis, and inhibiting these cells improves the condition. It may be that some of these effects become worse with age.

Additionally, oxidation may play some role in the progress of osteoarthritis. Oxidation is a normal byproduct of cell metabolism, but signs of oxidation are found at higher levels in the joints of osteoarthritis patients than in people who do not have the condition. Abnormal levels of oxidation may be linked to the processes that cause degradation and death of joint cartilages, exacerbating osteoarthritis. This oxidation may trigger abnormalities in mitochondria—small units in each cell that generate energy. Mitochondria with some specific genetic sequences are more susceptible to this kind of damage.

Cells have many ways of regulating oxidation, some of which are regulated by NRF2. NRF2 activates genes that decrease joint pain early on, protects cartilage from degradation, and also prevents damage to mitochondria. Mice with reduced NRF2 function display more severe osteoarthritis as well as reduced bone mass and bone strength and NRF2 may also play a role in the severity of other diseases, including osteoporosis. However, overexpression of NRF2 could also prevent the formation of new cartilage, suggesting the need for a precise balance of NRF2 in the body.

Stem cells could provide a way to use NRF2 to treat osteoarthritis and other conditions. Plant-based medicine, including those derived from curcumin and Radix astragali, could also be used to activate NRF2 or mimic its function, by reducing oxidation and promoting cartilage and bone health.

Written by  C. I. Villamil

Reference: Marchev et al. 2017. Oxidative stress and chronic inflammation in osteoarthritis… Ann NY Acad Sci.