终端补充复合体沉积在软骨细胞上促进了与年龄和创伤相关的骨关节炎的早衰
Leonie Ruths1, Jana Hengge1, Graciosa Q Teixeira2
1Division for Biochemistry of Joint and Connective Tissue Diseases, Department of Orthopedics, Ulm University Medical Center, Ulm, Germany.
Frontiers in immunology
|January 29, 2025
概括
补体激活和终端补体复合体 (TCC) 沉积驱动骨关节炎 (OA) 中的冠状腺发育. 向TCC形成可能提供一种未来的策略,通过减少TCC介导的细胞因子释放来减缓OA的进展.
科学领域:
- 免疫学 免疫学 免疫学
- 类风湿病学 类风湿病学
- 细胞生物学 细胞生物学
背景情况:
- 补体系统在关节受伤后在局部激活,导致终端补体复合体 (TCC) 沉积.
- 细分的TCC沉积会改变人类关节细胞 (hAC) 并增加炎症性细胞因子的释放.
- 慢性炎症是骨关节炎 (OA) 发生的已知因素之一.
研究的目的:
- 调查TCC沉积是否有助于衰老和损伤后软骨的压力诱导过早衰老 (SIPS).
- 探索TCC介导途径在冠状细胞衰老中的作用.
主要方法:
- 使用老化小鼠模型 (CD59-ko,C6-缺乏,WT) 和ex vivo人类/猪软骨实验.
- 探索者经历了创伤,并通过人类血清 (HS) 激活了补体.
- 研究了TCC抑制 (CLU),抗氧化剂 (NAC) 和细胞因子抑制剂 (Sarilumab,STAT3-IN-1,IL-1RA) 对衰老标志物 (CDKN1A,CDKN2A) 的影响.
主要成果:
- CD59-ko小鼠表现出更严重的OA,老化标志物和炎症性细胞因子 (IL1b,Il6) 的增加.
- 人类软骨创伤 + HS增加了CDKN1A,CDKN2A和IL6;CLU抑制了这一点.
- NAC没有抗衰老作用;细胞因子抑制剂显示了减少猪组织衰老标志物的趋势.
结论:
- 补充剂激活和TCC沉积与OA中的冠状体发生有关,无论是与年龄相关的还是创伤引起的.
- 由TCC介导的细胞因子释放,而不是氧化应激,似乎驱动了SIPS类型的表型.
- 抑制TCC形成为OA进展提供了一个潜在的治疗策略.
相关概念视频
Growth of Cartilage and Bone Tissue
3.0K
Chondrocytes form a temporary cartilaginous model by dividing and secreting a thick gel-like extracellular matrix. Once the chondrocytes undergo programmed cell death, osteoblasts enter the site of the cartilaginous model. The process of replacing the temporary cartilaginous model with bone in an ordered manner is called endochondral ossification. In endochondral ossification, not all of the cartilage is replaced by bone tissue. Some cartilage that performs a protective and supportive function...
3.0K
Bone Formation by Endochondral Ossification
3.7K
Bone formation, or ossification, begins around the sixth to seventh week of embryonic development. Most bones develop from a cartilaginous template through the process of endochondral ossification. Cartilage formation begins when clusters of mesenchymal cells differentiate into chondrocytes. These chondrocytes proliferate rapidly and secrete an extracellular matrix that becomes encased in a membrane called the perichondrium. The resulting cartilage model provides a template that resembles the...
3.7K
Bone Remodeling
38.1K
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.
38.1K
Fractures: Bone Repair
2.9K
Treatment for a fracture is based on the type of break, the bone affected, and the patient's age.
Minor fractures with no bone displacement are treated by immobilizing the fractured bone using a cast or splint. However, in the case of fractures with displaced bones, the broken bones are repositioned before immobilization to ensure successful healing without deformation and loss of function. The realignment of fractured bone ends is performed through a process called reduction. If the...
Minor fractures with no bone displacement are treated by immobilizing the fractured bone using a cast or splint. However, in the case of fractures with displaced bones, the broken bones are repositioned before immobilization to ensure successful healing without deformation and loss of function. The realignment of fractured bone ends is performed through a process called reduction. If the...
2.9K
Glycosaminoglycans
4.7K
Glycosaminoglycans (GAGs), also known as mucopolysaccharides, are long and linear polymers comprising of specific repeating disaccharides - the amino sugar that can be N-acetylglucosamine or N-acetylgalactosamine, and a uronic acid that is usually glucuronic acid or iduronic acid.
GAGS are found in the extracellular matrix of vertebrates, invertebrates, and bacteria. Due to their polar nature they attract water, and serve as excellent lubricants or shock absorbers in an animal body.
Hyaluronic...
GAGS are found in the extracellular matrix of vertebrates, invertebrates, and bacteria. Due to their polar nature they attract water, and serve as excellent lubricants or shock absorbers in an animal body.
Hyaluronic...
4.7K
Extracellular Matrix
2.7K
Unlike epithelial tissue, which is composed of cells closely packed with little or no extracellular space in between, connective tissue cells are dispersed in a matrix. This extracellular matrix (ECM) is composed of fibrous proteins like collagen, elastin, and fibronectin in a ground substance consisting of interstitial fluid, cell adhesion proteins, and proteoglycans. The proteoglycans form a gel-like material in the spaces between cells and provide hydration, buffering, binding, and force...
2.7K


