Research Progress of Ferroptosis Regulatory Network and Bone Remodeling in Osteoporosis

Yan, Chunlu; Zhang, Jinlong; An, Fangyu; Wang, Jiayu; Shi, Yong; Yuan, Ling‐Qing; Lv, Donghui; Zhao, Yongtao; Wang, Yongfeng

doi:10.3389/fpubh.2022.910675

Cited by 25 publications

(13 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many studies have shown that abnormal cell death of osteocytes is involved in the occurrence and development of orthopedic diseases, including bone marrow injury, osteoporosis, osteoarthritis and osteosarcoma. [45,46] Our findings support the concept that osteocytic ferroptosis plays an important role in the maintenance of bone homeostasis. In the mice after bilateral ovariectomy, after GPX4 was knocked out, severe ferroptosis occurred in the osteocytes, while the bone mass of the mice further decreased, and the bone microstructure further deteriorated, indicating that ferroptosis of the osteocytes promoted bone loss.…”

Section: Discussionsupporting

confidence: 83%

Ferroptosis in Osteocytes as a Target for Protection Against Postmenopausal Osteoporosis

Jiang,

Qi,

et al. 2024

Advanced Science

View full text Add to dashboard Cite

Ferroptosis is a necrotic form of iron‐dependent regulatory cell death. Estrogen withdrawal can interfere with iron metabolism, which is responsible for the pathogenesis of postmenopausal osteoporosis (PMOP). Here, it is demonstrated that estrogen withdrawal induces iron accumulation in the skeleton and the ferroptosis of osteocytes, leading to reduced bone mineral density. Furthermore, the facilitatory effect of ferroptosis of osteocytes is verified in the occurrence and development of postmenopausal osteoporosis is associated with over activated osteoclastogenesis using a direct osteocyte/osteoclast coculture system and glutathione peroxidase 4 (GPX4) knockout ovariectomized mice. In addition, the nuclear factor erythroid derived 2‐related factor‐2 (Nrf2) signaling pathway is confirmed to be a crucial factor in the ferroptosis of osteocytic cells. Nrf2 regulates the expression of nuclear factor kappa‐B ligand (RANKL) by regulating the DNA methylation level of the RANKL promoter mediated by DNA methyltransferase 3a (Dnmt3a), which is as an important mechanism in osteocytic ferroptosis‐mediated osteoclastogenesis. Taken together, this data suggests that osteocytic ferroptosis is involved in PMOP and can be targeted to tune bone homeostasis.

show abstract

Section: Discussionsupporting

confidence: 83%

Ferroptosis in Osteocytes as a Target for Protection Against Postmenopausal Osteoporosis

Jiang,

Qi,

et al. 2024

Advanced Science

View full text Add to dashboard Cite

show abstract

“…Several factors have been demonstrated to contribute to the development of osteoporosis, such as inflammatory response, metabolic disorders, and genetic conditions (Ebeling et al, 2022). A few recent studies have established the involvement of ferroptosis in the progression of osteoporosis and the disruption of the balance between osteoclastic and osteogenic activities (Liu et al, 2022b;Gao et al, 2022;Yan et al, 2022). Another report showed that dexamethasone could weaken the activity of intracellular antioxidant systems through downregulation of the SLC7A11/ GPX4 signaling, thereby enhancing the ferroptosis sensitivity of MC3T3-E1 and MOLY4 preosteoblasts and contributing to glucocorticoid-induced osteonecrosis (Sun et al, 2022).…”

Section: Osteoporosismentioning

confidence: 99%

Current insights into the functional roles of ferroptosis in musculoskeletal diseases and therapeutic implications

Zhang

Yan

Cai

et al. 2023

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Ferroptosis is a novel type of cell death associated with iron accumulation and excessive lipid peroxidation. Elucidating the underlying molecular mechanisms of ferroptosis is intensively related to the development and treatment of multiple diseases, including musculoskeletal disorders. Moreover, in vitro and in vivo studies have shown the importance of oxidative stress in musculoskeletal conditions such as osteoporosis, osteoarthritis, rheumatoid arthritis, and osteosarcoma. Ferroptosis-derived clinical management of musculoskeletal diseases offers tremendous and attractive opportunities. Notably, ferroptosis agonists have been proven to enhance the sensitivity of osteosarcoma cells to conventional therapeutic strategies. In this review, we have mainly focused on the implications of ferroptosis regulation in the pathophysiology and therapeutic response of musculoskeletal disorders. Understanding roles of ferroptosis for controlling musculoskeletal diseases might provide directions for ferroptosis-driven therapies, which could be promising for the development of novel therapeutic strategies.

show abstract

“…The system xc ‐ ‐GSH‐GPX4 pathway dysregulation and iron overload are the main ferroptosis‐initiating factors 16 . Growing evidence has confirmed the vital role of ferroptosis in the maintenance of bone homeostasis 17 . Ferroptosis of osteoporotic target cells including osteoblasts and osteocytes is proposed as the novel and potential mechanism of osteoporosis 18,19 .…”

Section: Introductionmentioning

confidence: 99%

“…16 Growing evidence has confirmed the vital role of ferroptosis in the maintenance of bone homeostasis. 17 Ferroptosis of osteoporotic target cells including osteoblasts and osteocytes is proposed as the novel and potential mechanism of osteoporosis. 18,19 Serum from osteoporotic patients is found to induce ferroptosis of osteoblasts thus inhibiting osteogenic differentiation and mineralization.…”

Section: Introductionmentioning

confidence: 99%

Interaction between ferroptosis and TNF‐α: Impact in obesity‐related osteoporosis

Chen

Liu

et al. 2023

The FASEB Journal

View full text Add to dashboard Cite

The relationship of obesity and osteoporosis has been widely studied over the past years. However, the implications of obesity for bone health remain controversial, and the underlying molecular mechanism is not yet fully understood.This study demonstrated that high-fat diet-induced obesity leads to significantly decreased bone volume/tissue volume (BV/TV), trabecular number (Tb.N), and cortical thickness (Ct.Th) of male rat femur after mechanical loading effects of body weight were controlled. HFD-induced obese rats exhibited attenuated expression of ferroptosis inhibitory protein SLC7A11 and GPX4 in bone tissues, which was correlated with elevated serum TNF-α concentration. Ferroptosis inhibitor administration could effectively rescue decreased osteogenesis-associated type H vessels and osteoprogenitors, and downregulate serum levels of TNF-α to ameliorate bone loss in obese rats. Since ferroptosis and TNF-α both affect bone and vessel formation, we further investigated the interaction between ferroptosis and TNF-α, and its impact in osteogenesis and angiogenesis in vitro. In human osteoblast-like MG63 and umbilical vein endothelial cells (HUVEC), TNF-α/ TNFR2 signaling promoted cystine uptake and GSH biosynthesis to provide protection against low-dose ferroptosis inducer erastin. While, TNF-α/TNFR1 facilitated ferroptosis in the presence of high-dose erastin through ROS accumulation.

show abstract

Research Progress of Ferroptosis Regulatory Network and Bone Remodeling in Osteoporosis

Cited by 25 publications

References 48 publications

Ferroptosis in Osteocytes as a Target for Protection Against Postmenopausal Osteoporosis

Ferroptosis in Osteocytes as a Target for Protection Against Postmenopausal Osteoporosis

Current insights into the functional roles of ferroptosis in musculoskeletal diseases and therapeutic implications

Interaction between ferroptosis and TNF‐α: Impact in obesity‐related osteoporosis

Contact Info

Product

Resources

About