Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany.
Inserm UMR1132 and Paris Diderot University, Paris, France.
Osteoarthritis Cartilage. 2021 Jan;29(1):78-88. doi: 10.1016/j.joca.2020.09.008. Epub 2020 Nov 21.
The human matrilin-3 T303M (in mouse T298M) mutation has been proposed to predispose for osteoarthritis, but due to the lack of an appropriate animal model this hypothesis could not be tested. This study was carried out to identify pathogenic mechanisms in a transgenic mouse line by which the mutation might contribute to disease development.
A mouse line carrying the T298M point mutation in the Matn3 locus was generated and features of skeletal development in ageing animals were characterized by immunohistology, micro computed tomography, transmission electron microscopy and atomic force microscopy. The effect of transgenic matrilin-3 was also studied after surgically induced osteoarthritis.
The matrilin-3 T298M mutation influences endochondral ossification and leads to larger cartilage collagen fibril diameters. This in turn leads to an increased compressive stiffness of the articular cartilage, which, upon challenge, aggravates osteoarthritis development.
The mouse matrilin-3 T298M mutation causes a predisposition for post-traumatic osteoarthritis and the corresponding knock-in mouse line therefore represents a valid model for investigating the pathogenic mechanisms involved in osteoarthritis development.
人类的肌腱膜素-3 T303M（在小鼠中为 T298M）突变被认为易患骨关节炎，但由于缺乏适当的动物模型，这一假设无法得到验证。本研究旨在通过携带 T298M 点突变的 Matn3 基因座的转基因小鼠系来确定致病机制，突变可能通过这些机制促进疾病的发展。
生成了携带 Matn3 基因座 T298M 点突变的小鼠系，并通过免疫组织化学、微计算机断层扫描、透射电子显微镜和原子力显微镜来描述老年动物骨骼发育的特征。还研究了转基因肌腱膜素-3 对手术诱导骨关节炎的影响。
肌腱膜素-3 T298M 突变影响软骨内骨化，并导致更大的软骨胶原纤维直径。这反过来又导致关节软骨的压缩刚度增加，在受到挑战时，会加重骨关节炎的发展。
小鼠肌腱膜素-3 T298M 突变导致创伤后骨关节炎的易感性，相应的基因敲入小鼠系因此代表了研究骨关节炎发展相关致病机制的有效模型。
