The significance of the extracellular matrix proteins COMP and collagen IX in the mechanical function of articular cartilage and in the pathogenesis of osteoarthritis

细胞外基质蛋白 COMP 和胶原 IX 在关节软骨机械功能和骨关节炎发病机制中的意义

• 批准号: 385747122
• 负责人: Professorin Dr. Anja Niehoff
• 金额: --
• 依托单位: Institut für Biomechanik und Orthopädie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/385747122?language=en
• 关键词: significance; extracellular; matrix; proteins; COMP

Osteoarthritis, the most common degenerative joint disease worldwide, is characterized by an imbalance between synthesis and degradation of the extracellular matrix (ECM) in articular cartilage. The ECM is composed of the proteoglycan aggrecan and heterotypic fibrils consisting of collagen II and XI. These two suprastructures are organized together with various non-collagenous glycoproteins in a molecular network that determines the mechanical properties of the tissue thereby defining its function. In recent years, we have worked intensively on two proteins interconnecting the two suprastructures, the glycoprotein cartilage oligomeric matrix protein (COMP) and collagen IX. Both proteins are localized at the surface of collagen fibrils and play a key role as adapter molecules mediating the integrity of the ECM. Further, their expression is mechanosensitive and they regulate the formation and diameter of collagen fibrils. This suggests that COMP and collagen IX are important for the mechanotransduction and integrity of articular cartilage. The aim of this project is to characterize their role in detail in mouse models and cell culture models. We hypothesize that both proteins contribute to the pathogenesis of osteoarthritis induced by mechanical stress. Both cellular and molecular biology techniques will be used. The long-term goal is to gain more insight into the biomechanical function of adapter molecules in cartilage function to better understand the development of osteoarthritis and to generate new treatments for this disease.

骨关节炎是世界上最常见的退行性关节疾病，其特征是关节软骨中细胞外基质(ECM)的合成和降解失衡。细胞外基质由蛋白多糖和由II型和XI型胶原组成的异型纤维组成。这两种超结构与各种非胶原性糖蛋白一起组成了一个分子网络，该网络决定了组织的机械性能，从而定义了其功能。近年来，我们一直致力于研究连接这两种超结构的两种蛋白质，糖蛋白软骨低聚基质蛋白(COMP)和IX型胶原。这两种蛋白都定位于胶原纤维表面，并作为调节细胞外基质完整性的接头分子发挥关键作用。此外，它们的表达是机械敏感的，它们调节胶原纤维的形成和直径。提示COMP和IX型胶原在关节软骨的力学转导和完整性中起重要作用。这个项目的目的是详细描述它们在小鼠模型和细胞培养模型中的作用。我们假设这两种蛋白都参与了机械应力引起的骨性关节炎的发病机制。将同时使用细胞和分子生物学技术。长期目标是更深入地了解软骨功能中适配分子的生物力学功能，更好地了解骨关节炎的发展，并为这种疾病创造新的治疗方法。

项目成果

Neutral Sphingomyelinase 2 (SMPD3)-Deficiency in Mice Causes Chondrodysplasia with Unimpaired Skeletal Mineralization.

• DOI: 10.1016/j.ajpath.2019.05.008
• 发表时间: 2019-09
• 期刊: The American journal of pathology
• 作者: W. Stoffel;Ina Hammels;B. Jenke;Inga Schmidt-Soltau;A. Niehoff

The Matrilin-3 T298M Mutation Predisposes for Post-Traumatic Osteoarthritis in a Knock-in Mouse Model.

Matrilin-3 T298M 突变易导致敲入小鼠模型中的创伤后骨关节炎

• DOI: 10.1016/j.joca.2020.09.008
• 发表时间: 2021
• 期刊: Osteoarthritis and cartilage
• 影响因子: 7
• 作者: Seifer P;Fleischhauer L;Heilig J;Bloch W;Sonntag S;Schmerling D;Clausen- Schaumann H;Aszodi A;Niehoff A;Cohen-Solal M;Paulsson M;Wagener R;Zaucke F
• 通讯作者: Zaucke F

Impact of knee joint loading on fragmentation of serum cartilage oligomeric matrix protein

• DOI: 10.1002/jor.24586
• 发表时间: 2020-01-15
• 期刊: JOURNAL OF ORTHOPAEDIC RESEARCH
• 影响因子: 2.8
• 作者: Firner, Sara;Zaucke, Frank;Niehoff, Anja
• 通讯作者: Niehoff, Anja

THE EFFECT OF FORCED RUNNING EXERCISE ON THE KNEE JOINT ARTICULAR CARTILAGE OF CARTILAGE OLIGOMERIC MATRIX PROTEIN DEFICIENT MICE

强迫跑步运动对软骨寡聚基质蛋白缺陷小鼠膝关节软骨的影响

• DOI: 10.1016/j.joca.2022.02.221
• 发表时间: 2022
• 期刊: Osteoarthritis and Cartilage
• 影响因子: 7
• 作者: Weyers M;Mählich D;Dreiner M;Eckes B;Niehoff A
• 通讯作者: Niehoff A