Oxidative stress in bone remodeling: role of antioxidants

Abstract

SummaryROS are highly reactive molecules which consist of a number of diverse chemical species, including radical and non-radical oxygen species. Oxidative stress occurs as a result of an overproduction of ROS not balanced by an adequate level of antioxidants. The natural antioxidants are: thiol compounds among which GSH is the most representative, and non-thiol compounds such as polyphenols, vitamins and also various enzymes. Many diseases have been linked to oxidative stress including bone diseases among which one of the most important is the osteoporosis. The redox state changes are also related to the bone remodeling process which allows the continuous bone regeneration through the coordinated action of bone cells: osteoclasts, osteoblasts and osteocytes. Changes in ROS and/or antioxidant systems seem to be involved in the pathogenesis of bone loss. ROS induce the apoptosis of osteoblasts and osteocytes, and this favours osteoclastogenesis and inhibits the mineralization and osteogenesis. Excessive osteocyte apoptosis correlates with oxidative stress causing an imbalance in favor of osteoclastogenesis which leads to increased turnover of bone remodeling and bone loss. Antioxidants either directly or by counteracting the action of oxidants contribute to activate the differentiation of osteoblasts, mineralization process and the reduction of osteoclast activity. In fact, a marked decrease in plasma antioxidants was found in aged or osteoporotic women. Some evidence shows a link among nutrients, antioxidant intake and bone health. Recent data demonstrate the antioxidant properties of various nutrients and their influence on bone metabolism. Polyphenols and anthocyanins are the most abundant antioxidants in the diet, and nutritional approaches to antioxidant strategies, in animals or selected groups of patients with osteoporosis or inflammatory bone diseases, suggest the antioxidant use in anti-resorptive therapies for the treatment and prevention of bone loss.

<i>Sargassum serratifolium</i> attenuates RANKL-induced osteoclast differentiation and oxidative stress through inhibition of NF-κB and activation of the Nrf2/HO-1 signaling pathway

“…However, they certainly play important signaling roles in the process of osteoclastogenesis (21,22). Many previous studies have shown that ROS accumulation can increase the expression of RANKL in osteoclasts and enhance their survival and proliferation (19,23,24). In addition, ROS can act as upstream molecules for activation of NF-κB and NFATc1 to promote transcription of osteoclastspecific genes at the onset of osteoclastogenesis.…”

“…In addition, ROS can act as upstream molecules for activation of NF-κB and NFATc1 to promote transcription of osteoclastspecific genes at the onset of osteoclastogenesis. On the other hand, excessive production of ROS will inhibit the differentiation of osteoblasts and induce death of osteocytes as well as osteocytes, leading to bone formation imbalance (19,20). Therefore, inhibiting or eliminating ROS production can prevent pathological causes of various diseases associated with functional activation of osteoclasts by oxidative stress.…”

“…As oxidative stress also plays a critical role in the osteoclast differentiation and bone resorption (19,20), we then investigated whether EESS could suppress RANKL-induced generation of ROS. Our flow cytometry results indicated that the level of ROS markedly increased in RANKL-stimulated cells; however, the increase in ROS content was reduced in a concentration-dependent manner by addition of EESS.…”

“…Oxidative stress caused by excessive production of reactive oxygen species (ROS) has been reported to inhibit osteoblast survival and function, thereby inhibiting bone formation (19,20). Excessive ROS can also cause bone destruction by exerting oxidative damage to all cellular biomolecules such as proteins, lipids and nucleic acids (21,22).…”

“…Excessive ROS can also cause bone destruction by exerting oxidative damage to all cellular biomolecules such as proteins, lipids and nucleic acids (21,22). In addition, the overproduction of ROS has been demonstrated to increase the expression of RANKL by osteoclasts, thereby activating osteoclasts and enhancing bone resorption capacity, indicating that ROS play an important role in osteoclastogenesis (19,23,24). Most cells have endogenous defense strategies to eliminate damage caused by excessive ROS production.…”