Regulation of cytokine-dependent calcification of cartilage tissue by NPP1 and syndecan-4

NPP1 和 syndecan-4 对细胞因子依赖性软骨组织钙化的调节

• 批准号: 189929146
• 负责人: Professor Dr. Thomas Pap
• 金额: --
• 依托单位: Institut für Muskuloskelettale Medizin
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/189929146?language=en
• 关键词: Regulation; cytokine; dependent; calcification; cartilage

Calcification of tissue occurs physiologically during the longitudinal growth of bones but is induced also in diseases of the skeletal system such as osteoarthritis (OA). As in physiology, pathological tissue calcification is linked to chondrocyte differentiation, and the nucleotide pyrophosphatase phosphodiesterase NPP1 has been implicated in this process. Moreover, some data indicate that inflammatory factors such as interleukin (IL)-1 promote tissue calcification through suppression of NPP1. Based on previous work of our group that has linked cartilage calcification in OA to chondrocyte hypertrophy and demonstrated the involvement of the transmembrane heparan sulfate proteoglycan syndecan-4 in IL-1 signalling, we want to investigate the regulation of cartilage calcification by NPP1 and syndecan-4. Through in vitro experiments on isolated chondrocytes and osteoblasts as well as in vivo studies in NPP1- and syndecan-4 deficient mice, we want to follow the hypothesis that inflammatory mediators such as IL-1 promote tissue calcification in OA by regulating NPP1 and that syndecan-4 is involved in this process. The project will provide important insights into the role and mechanisms of pathological calcification of cartilage in the pathogenesis of OA.

组织的钙化在生理上发生在骨的纵向生长期间，但也在骨骼系统疾病如骨关节炎（OA）中诱导。在生理学上，病理性组织钙化与软骨细胞分化有关，核苷酸焦磷酸酶磷酸二酯酶NPP 1参与了这一过程。此外，一些数据表明，炎症因子如白细胞介素（IL）-1通过抑制NPP 1促进组织钙化。基于我们小组先前的工作，将OA中的软骨钙化与软骨细胞肥大联系起来，并证明跨膜硫酸乙酰肝素蛋白聚糖syndecan-4参与IL-1信号传导，我们希望研究NPP 1和syndecan-4对软骨钙化的调节。通过对分离的软骨细胞和成骨细胞的体外实验以及对NPP 1和syndecan-4缺陷小鼠的体内研究，我们希望遵循这样的假设，即炎症介质如IL-1通过调节NPP 1促进OA中的组织钙化，而syndecan-4参与了这一过程。该项目将提供重要的洞察软骨的病理性钙化的作用和机制，在OA的发病机制。

项目成果

Critical role for syndecan-4 in dendritic cell migration during development of allergic airway inflammation

• DOI: 10.1038/ncomms8554
• 发表时间: 2015-07-01
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Polte, Tobias;Petzold, Susanne;Averbeck, Marco
• 通讯作者: Averbeck, Marco

Early structural changes in cartilage and bone are required for the attachment and invasion of inflamed synovial tissue during destructive inflammatory arthritis

• DOI: 10.1136/annrheumdis-2011-200386
• 发表时间: 2012-06-01
• 期刊: ANNALS OF THE RHEUMATIC DISEASES
• 影响因子: 27.4
• 作者: Korb-Pap, Adelheid;Stratis, Athanasios;Redlich, Kurt
• 通讯作者: Redlich, Kurt

Articular Cartilage Calcification of the Humeral Head Is Highly Prevalent and Associated With Osteoarthritis in the General Population

• DOI: 10.1002/jor.23227
• 发表时间: 2016-11-01
• 期刊: JOURNAL OF ORTHOPAEDIC RESEARCH
• 影响因子: 2.8
• 作者: Hawellek, Thelonius;Hubert, Jan;Niemeier, Andreas
• 通讯作者: Niemeier, Andreas