Nur77 Prevents Osteoporosis by Inhibiting the NF‐κB Signalling Pathway and Osteoclast Differentiation

Abstract

Osteoporosis is a metabolic systemic bone disease that typically manifests as decreased bone mass and increased bone fragility. 1 With the ageing of the worldwide population, the social and economic burdens of osteoporosis remain steady. According to a previous study, approximately 15,000 osteoporotic fractures occur in the United States every year, 2 which not only severely affects patients' quality of life but also imposes heavy burdens on medical and health systems. The currently known risk factors for osteoporosis include age, 3 vitamin D and calcium deficiencies, 4 insufficient exercise, 5 smoking, 6 drinking, 7 oestrogen withdrawal 8 and

Oral Milk-Derived Extracellular Vesicles Inhibit Osteoclastogenesis and Ameliorate Bone Loss in Ovariectomized Mice by Improving Gut Microbiota

“…The main drivers of osteoclastogenesis are the increases in receptor activator of nuclear factor-κB ligand (RANKL) and pro-inflammatory cytokines and decreases in anti-inflammatory cytokines. 6 Changes of specific gut microbiota and their metabolites could act on osteoporosis by affecting the bone resorption of osteoclasts. 7 Changes in the abundance of Firmicutes and Bacteroidetes can be used as potential indicators of osteoclast differentiation and osteoporosis.…”

“…Postmenopausal osteoporosis, the most common bone disease, is mainly due to the excessive activation of osteoclastogenesis after the decline of estrogen levels in the body, which accelerates bone turnover and results in bone loss. The main drivers of osteoclastogenesis are the increases in receptor activator of nuclear factor-κB ligand (RANKL) and pro-inflammatory cytokines and decreases in anti-inflammatory cytokines . Changes of specific gut microbiota and their metabolites could act on osteoporosis by affecting the bone resorption of osteoclasts .…”

Qizhi Kebitong Formula Ameliorates Streptozocin-Induced Diabetic Osteoporosis through Regulating the PI3K/Akt/NF-κB Pathway

“…Among them, Akt was identified as a unique signaling intermediate in bone homeostasis that controlled the differentiation of osteoblasts and osteoclasts, which was a direct downstream target of PI3K to inhibit the release of inflammatory factors [32][33][34][35][36]. Moreover, NF-κB was also a key downstream factor of the PI3K/Akt pathway, which enhanced the degree of inflammatory response and promoted the differentiation of osteoclast precursors [37,38]. Meanwhile, the PI3K/Akt signaling pathway not only affects inflammatory factors such as NF-κB and TNF-α but also induced the inflammatory reaction in the internal environment of the body.…”

Therapeutic potential of NR4A1 in cancer: Focus on metabolism

“…Furthermore, NR4A1 interacts, and blocks binds and sequesters Liver kinase B1 (LKB1) in the nucleus, then releases and shuttles LKB1 to the cytoplasm, thereby attenuating AMP-activated protein kinase (AMPK) activation to treat metabolic diseases such as streptozotocin-induced diabetes ( 37 ). In osteoclast, knockout of NR4A1 can promote the differentiation of RAW264.7 by activating the NF-κB signaling pathway, in order to decrease the expression of IκB-α and induce IKK-β ( 23 ). Additionally, NR4A1 translocated from nucleus to mitochondria, then interacted with tumor necrosis factor receptor-associated factor 2 (TRAF2), leading to TRAF2 ubiquitination.…”