The Matrilin-3 T298M Mutation Predisposes for Post-Traumatic Osteoarthritis in a Knock-in Mouse Model.
The Matrilin-3 T298M Mutation Predisposes for Post-Traumatic Osteoarthritis in a Knock-in Mouse Model.
复制标题
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
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发表时间：
2021
影响因子：
7
通讯作者：
Zaucke F
中科院分区：
文献类型：
--
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
人类matrilin-3 T303 M（小鼠T298 M）突变被认为是骨关节炎的易感基因，但由于缺乏合适的动物模型，这一假设无法得到验证。本研究进行了识别致病机制的转基因小鼠线的突变可能有助于疾病development.MethodsA小鼠线携带T298 M点突变在theMatn 3基因座产生和功能的骨骼发育在老龄动物的特点是通过免疫组织学，显微计算机断层扫描，透射电子显微镜和原子力显微镜。转基因matrilin-3的效果也进行了研究后，手术诱导osteoarthritis.ResultsThe matrilin-3 T298 M突变的影响endochondriosisation，并导致较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，这在挑战时，increasates骨关节炎development.ConclusionsThe小鼠matrilin-3 T298 M突变导致创伤后骨关节炎的易感性和相应的敲入小鼠线，因此代表了一个有效的模型，用于调查参与骨关节炎发展的致病机制。
ObjectiveThe 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.MethodsA mouse line carrying the T298M point mutation in theMatn3locus 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.ResultsThe 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.ConclusionsThe 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.
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影响因子：
5.3
作者：
Budde, B;Blumbach, K;Grässel, S
通讯作者：
Grässel, S
影响因子：
6
作者：
van der Weyden, Louise;Wei, Lei;Chen, Qian
通讯作者：
Chen, Qian
由编码 Matrilin-3 (T120M) 的基因纯合错义突变导致的脊椎外干骺端发育不良
影响因子：
2.5
作者：
L. Das;V. Dhiman;W. Van Hul;A. Bhansali;Y. Gogate;E. Steenackers;G. Mortier;S. Bhadada
通讯作者：
S. Bhadada
影响因子：
4.1
作者：
Muschter, Dominique;Fleischhauer, Lutz;Graessel, Susanne
通讯作者：
Graessel, Susanne
天然软骨基质蛋白（CMP）。
影响因子：
4.8
作者：
N. Hauser;M. Paulsson
通讯作者：
M. Paulsson