Necroptosis: A new target for prevention of osteoporosis
Xinli Hu1,2, Zheng Wang1,2, Chao Kong1,2
1Department of Orthopedics, Xuanwu Hospital, Capital Medical University, Beijing, China.
Abstract:
Multiple causes may contribute to osteoporosis, characterized by a loss in bone mass and density as a consequence of the degradation of bone microstructure and a resultant rise in bone fragility. Recently, increasing attention has been paid to the role of necroptosis in the development of osteoporosis. Necroptosis is orchestrated by a set of proteins known as receptor-interacting protein kinase (RIPK)1, RIPK3, and mixed lineage kinase domain-like protein (MLKL). A necrosome is formed by MLKL, RIPK1, RIPK3, and RIPK3-RIPK3. A dissociated MLKL forms pores in the plasma membrane and eventually leads to necroptosis after translocating from the necrosome. In this review, we discuss a detailed understanding of necroptosis and its associated processes, a better understanding of its interactions with osteoclasts, osteoblasts, and osteocytes, and the associations between necroptosis and diabetic osteoporosis, steroid-induced osteoporosis, and postmenopausal osteoporosis. In addition, a variety of experimental medicines capable of modulating crucial necroptosis processes are highlighted. It's important to note that this is the first review paper to consolidate current data on the role of necroptosis in osteoporosis, and it offers fresh hope for the future treatment of this disease.
Insights
Necroptosis, a form of programmed cell death involving RIPK1, RIPK3, and MLKL, plays a key role in osteoporosis. This review explores necroptosis
Area of Science:
- Biomedical Science
- Cell Biology
- Pathology
Background:
- Osteoporosis is characterized by reduced bone mass and microarchitectural deterioration, increasing fracture risk.
- Emerging evidence implicates necroptosis, a regulated form of necrosis, in the pathogenesis of osteoporosis.
- Necroptosis is mediated by a complex of proteins including RIPK1, RIPK3, and MLKL.
Purpose of the Study:
- To provide a comprehensive review of the role of necroptosis in osteoporosis.
- To elucidate the molecular mechanisms linking necroptosis to bone cells (osteoclasts, osteoblasts, osteocytes).
- To discuss the association between necroptosis and specific osteoporosis subtypes, including diabetic, steroid-induced, and postmenopausal osteoporosis.
Main Methods:
- Literature review synthesizing current research on necroptosis and osteoporosis.
- Analysis of molecular pathways involving RIPK1, RIPK3, and MLKL in bone biology.
- Examination of experimental therapeutics targeting necroptosis pathways.
Main Results:
- Necroptosis contributes to bone loss through its effects on bone remodeling cells.
- Specific osteoporosis types show distinct associations with necroptotic pathways.
- Targeting necroptosis presents a potential therapeutic strategy for osteoporosis.
Conclusions:
- Necroptosis is a significant factor in osteoporosis development and progression.
- Understanding necroptosis interactions with bone cells is crucial for therapeutic development.
- This review consolidates existing knowledge and highlights novel treatment avenues for osteoporosis.
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