化疗诱导的脂肪系细胞衰老导致骨质损失
Ganesh Kumar Raut1, Taylor Malachowski1, Anupama Melam1
1Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA.
Nature communications
|December 30, 2025
概括
化疗通过诱导特定骨髓细胞中的细胞衰老导致骨质损失. 准这种衰老途径或使用衰老药物可以防止骨损失,改善癌症患者的生活质量.
科学领域:
- 在瘤学瘤学.
- 骨生物学 骨生物学 骨生物学
- 细胞衰老 细胞衰老
背景情况:
- 化疗引起的骨损失是癌症治疗的常见,不太了解的副作用.
- 细胞衰老在各种与年龄相关的疾病和治疗毒性方面发挥着作用.
研究的目的:
- 为了研究化疗诱导的骨损失背后的机制.
- 确定治疗策略,以预防癌症患者的骨质损失.
主要方法:
- 在小鼠模型中进行全身化疗.
- 在骨髓群体中细胞衰老的分析.
- 评估骨质细胞形成和骨矿物质密度.
- 药理上抑制p38MAPK-MK2通路的作用.
- 使用老化药物达沙替尼和奎尔塞丁 (D+Q) 的治疗.
主要成果:
- 化疗诱导细胞衰老,特别是在骨髓脂肪系细胞 (CAR细胞和BMAds).
- 衰老细胞促进了RANKL介导的骨质结晶发生,导致显著的骨质损失.
- 抑制p38MAPK-MK2通路抑制了SASP和RANKL的产生,防止了骨质损失.
- 达沙替尼和奎尔丁治疗选择性地消除了衰老细胞,并防止了骨质损失.
结论:
- 在CAR细胞和BMAds中的细胞衰老是化疗诱导的骨损失的关键驱动因素.
- 准p38MAPK-MK2通路或使用D+Q等老化剂是有希望的治疗策略.
- 这些发现为保护骨完整性和提高癌症患者的生活质量提供了一种新的方法.
更多相关视频
09:32Drug-Induced Senescence in Liver Cells Promotes M2 Macrophage Polarization: Implications for Tyrosine Kinase Inhibitor-Associated Hepatotoxicity
Published on: October 17, 2025
386
08:34Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis
Published on: June 3, 2016
15.7K
相关概念视频
Bone Disorders
5.0K
Aging and its effect on bone remodeling is the most common cause of bone disorders. In young and healthy people, bone deposition and resorption happen at an equal rate to maintain optimal bone health.
Bone deposition is also affected by the levels of sex hormones like estrogen and testosterone that promote osteoblast activity and bone matrix synthesis. When the level of these hormones decreases due to aging, it causes a reduction in bone deposition. As a result, bone resorption by osteoclasts...
Bone deposition is also affected by the levels of sex hormones like estrogen and testosterone that promote osteoblast activity and bone matrix synthesis. When the level of these hormones decreases due to aging, it causes a reduction in bone deposition. As a result, bone resorption by osteoclasts...
5.0K
Osteoclasts in Bone Remodeling
3.8K
Osteoclasts are cells responsible for bone resorption and remodeling. They originate from hematopoietic progenitor cells present in the bone marrow. Numerous progenitor cells fuse to form multinucleated cells, each with 10-20 nuclei. A single osteoclast has a diameter of 150 to 200 µM. These cells have ruffled borders that break down the underlying bone tissue and release minerals such as calcium into the blood in bone resorption. Osteoclasts cling to bones with their ruffled edges during...
3.8K
The Intrinsic Apoptotic Pathway
8.2K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
8.2K
Bone Remodeling
40.2K
Bone remodeling is a continuous and balanced process of bone resorption by osteoclasts and bone formation by osteoblasts. In adults, it helps maintain bone mass and calcium homeostasis. While mechanical stress can stimulate turnover as part of the normal maintenance and reparative process, several hormones also regulate bone remodeling.
40.2K
Adaptive Mechanisms in Cancer Cells
6.9K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
6.9K
Lineage Commitment
4.0K
Commitment is the process whereby stem cells:
4.0K
