Bone remodeling is regulated by local factors that regulate bone-forming osteoblasts and boneresorbing osteoclasts, in addition to hormonal activity. Recent studies have shown that reactive oxygen species (ROS) act as an intracellular signal mediator for osteoclast differentiation. However the role of ROS on osteoblast differentiation is poorly understood. Here, we investigated the impact of ROS on osteoblastic differentiation of MC3T3-E1 cells. Osteogenic induction resulted in notable enhancement of mineralization and expression of osteogenic marker gene alkaline phosphatase, which were accompanied by an increase in ROS production. Additionally, we found that mitochondrial morphology dynamically changed from tubular reticulum to fragmented structures during the differentiation, suggesting that mitochondrial morphological transition is a novel osteoblast differentiation index. The antioxidant N-acetyl cysteine prevented not only ROS production but also mineralization and mitochondrial fragmentation. It is therefore suggested that the ROSdependent signaling pathways play a role in osteoblast differentiation accompanied by mitochondrial morphological transition.Bone is a dynamic organ that undergoes continuous remodeling while maintaining a balance between bone formation and resorbtion. Osteoblasts, which synthesize and mineralize new bone, and osteoclasts, which resorb bone, act in concert to maintain bone homeostasis. Bone mass density is maintained constant under the control of multiple systemic and local factors such as sex hormones, parathyroid hormone, growth hormone, and proinflammatory cytokines (21,22,25). Imbalanced functions of these two activities are involved in various types of bone diseases such as osteoporosis and vascular calcification, which are the major age-related diseases. To understand the pathogenic mechanism of these diseases, it is important to elucidate the regulatory mechanisms of the differentiation and activation of osteoclasts and osteoblasts. Although the physiological mechanisms of bone metabolism are becoming better understood, the intracellular signal transduction pathway that contributes to the regulation of differentiation and activation of osteoclasts and osteoblasts remains to be established. In this regard, it was recently reported that reactive oxygen species (ROS) act as an intracellular signal mediator for osteoclast differentiation, in which RANKL (receptor activator of NF-κB (nuclear factor κB) ligand) induces NADPH oxidase-derived ROS as an essential mechanism for osteoclast differentiation (10,15,18). However, the role of ROS on osteoblast differentiation remains largely uncertain. Mitochondria are crucial organelles involved in cellular energy production and in the regulation of numerous aspects of cellular activity including Ca 2+ signaling and apoptosis (5, 23). Furthermore, it has become evident in recent years that mitochondria
Edited by Vladimir Skulachev
Keywords:Cell death DNA damage Endoplasmic reticulum MG23 Ultraviolet light a b s t r a c tThe endoplasmic reticulum (ER) operates in adaptive responses to various stresses, dictating cell fate. Here we show that knockdown of the ER protein mitsugumin23 (MG23) enhances cell death induced by ultraviolet C (UVC), which causes DNA damage. The small heat shock protein aB-crystallin (aBC) is identified as a MG23 binding molecule and its knockdown facilitates death of UVCexposed cells. Conversely, aBC lowered UVC sensitivity when expressed as an ER-anchored form.Taken together, the results suggest that MG23 plays a protective role against UVC by accumulating aBC in the close vicinity of the ER.
Structured summary of protein interaction:MG23 physically interacts with aBC by anti tag coimmunoprecipitation (View interaction) MG23 physically interacts with aBC by two hybrid (View interaction)
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