低碳氧化OCN通过GPRC6A/HIF-1α级联抑制胆固醇细胞缩和骨关节炎的发展
Zhangzhen Du1,2,3, Yongqi Zhao1, Ke Zhang1,2
1Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, P.R. China.
International journal of biological sciences
|August 6, 2025
概括
低碳氧化骨质卡尔辛 (ucOCN) 显示在骨关节炎中具有保护作用. 补充ucOCN改善了软骨完整性,并减少了小鼠模型中的关键骨关节炎标志物.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 整形外科 整形外科 整形外科
背景情况:
- 骨质素 (OCN) 对于骨形成至关重要,与碳氧化OCN (cOCN) 结合酸.
- 脱碳氧化OCN (ucOCN) 具有除骨之外的内分泌功能,影响各种器官.
- 细胞外ucOCN在软骨细胞和骨关节炎 (OA) 中的作用还没有得到充分研究.
研究的目的:
- 调查细胞外低碳化骨质卡尔辛 (ucOCN) 在软骨细胞和骨关节炎中的作用.
- 探索ucOCN在调节OA相关变化的治疗潜力.
主要方法:
- 使用OCN淘汰 (OCN-/-) 鼠标来评估OCN的缺失.
- 分析了X型原体 (COL10) 和矩阵金属蛋白酶13 (MMP13) 的表达.
- 在小鼠关节炎模型中使用ucOCN,并检查软骨完整性.
- 通过ucOCN.研究了GPRC6A和HIF-1α通路的调节.
主要成果:
- 缺少OCN会增加胆红细胞中COL10和MMP13的表达.
- 在关节炎和OA中,突流体ucOCN水平下降.
- 升高的ucOCN降低了COL10a1和MMP13的调节,改善了关节炎模型中的软骨完整性.
- ucOCN调节了GPRC6A和HIF-1α通路,促进了TIMP3和自.
结论:
- 细胞外的ucOCN在软骨细胞和软骨中起着保护作用.
- ucOCN的使用表明了对骨关节炎的治疗潜力.
- ucOCN通过GPRC6A,HIF-1α,TIMP3和自途径发挥保护作用.
相关概念视频
Osteoclasts in Bone Remodeling
3.2K
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...
3.2K
GPCRs Regulate Adenylyl Cylase Activity
5.9K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.9K
Nitric Oxide Signaling Pathway
5.2K
Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure...
5.2K
TGF - β Signaling Pathway
7.6K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.6K
Growth of Cartilage and Bone Tissue
3.5K
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...
3.5K
Bone Formation by Endochondral Ossification
5.5K
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...
5.5K


