Nuclear factor erythroid-2-related factor 2 (Nrf2) plays an important role in maintaining cellular homeostasis, as it suppresses cell damage caused by external stimuli by regulating the transcription of intracellular defense-related genes. Accumulating evidence has highlighted the crucial role of reduction-oxidation (REDOX) imbalance in the development of bone-related diseases. Nrf2, a transcription factor linked to nuclear factor-erythrocyte 2, plays a pivotal role in the regulation of oxidative stress and induction of antioxidant defenses. Therefore, further investigation of the mechanism and function of Nrf2 in bone-related diseases is essential. Considerable evidence suggests that increased nuclear transcription of Nrf2 in response to external stimuli promotes the expression of intracellular antioxidant-related genes, which in turn leads to the inhibition of bone remodeling imbalance, improved fracture recovery, reduced occurrence of osteoarthritis, and greater tumor resistance. Certain natural extracts can selectively target Nrf2, potentially offering therapeutic benefits for osteogenic arthropathy. In this article, the biological characteristics of Nrf2 are reviewed, the intricate interplay between Nrf2-regulated REDOX imbalance and bone-related diseases is explored, and the potential preventive and protective effects of natural products targeting Nrf2 in these diseases are elucidated. A comprehensive understanding of the role of Nrf2 in the development of bone-related diseases provides valuable insights into clinical interventions and can facilitate the discovery of novel Nrf2-targeting drugs.

The hypoxia pathway not only regulates the organism to adapt to the special environment, such as short-term hypoxia in the plateau under normal physiological conditions, but also plays an important role in the occurrence and development of various diseases such as cancer, cardiovascular diseases, osteoporosis. Bone, as a special organ of the body, is in a relatively low oxygen environment, in which the expression of hypoxia-inducible factor (HIF)-related molecules maintains the necessary conditions for bone development. Osteoporosis disease with iron overload endangers individuals, families and society, and bone homeostasis disorder is linked to some extent with hypoxia pathway abnormality, so it is urgent to clarify the hypoxia pathway in osteoporosis to guide clinical medication efficiently. Based on this background, using the keywords “hypoxia/HIF, osteoporosis, osteoblasts, osteoclasts, osteocytes, iron/iron metabolism”, a matching search was carried out through the Pubmed and Web Of Science databases, then the papers related to this review were screened, summarized and sorted. This review summarizes the relationship and regulation between the hypoxia pathway and osteoporosis (also including osteoblasts, osteoclasts, osteocytes) by arranging the references on the latest research progress, introduces briefly the application of hyperbaric oxygen therapy in osteoporosis symptoms (mechanical stimulation induces skeletal response to hypoxic signal activation), hypoxic-related drugs used in iron accumulation/osteoporosis model study, and also puts forward the prospects of future research.

Background: Mitochondria are the primary organelles that regulate cellular bioenergetic metabolism and maintain homeostasis, providing essential structural support for optimal cell survival. Nonetheless, advancing age leads to cumulative damage to mitochondrial structure and functional integrity, which is a defining characteristic of biological aging and is closely linked to the emergence and progression of numerous age-related diseases, including neurodegenerative disorders, cardiovascular diseases, and metabolic disorders. Scope of review: This article offers a thorough summary and review of mitochondrial quality control (MQC), emphasizing numerous critical processes, including mitochondrial biosynthesis, dynamic remodeling (fusion and fission), and mitophagy. We thoroughly elucidate the molecular pathways that regulate MQC and demonstrate how age-related dysregulation precipitates cellular senescence, highlighting the transition from physiological maintenance to pathological malfunction, which ultimately culminates in cellular aging. Conclusions and implications: This study systematically elaborates the pathophysiological mechanisms in the field, comprehensively evaluates the clinical translational potential of targeting the MQC pathway, highlights the key objectives of “restoring mitochondrial plasticity and removing dysfunctional mitochondria”, and explores novel intervention strategies. The restoration of normal mitochondrial function in cells throughout aging is a very promising path for precision medicine therapeutics with great translational potential, according to recent state-of-the-art research. The development of novel therapeutic approaches to improve functional healthy mitochondria can effectively delay aging and reduce the rising global burden of age-related diseases.