Zhu Mengjie, Metzen Fabian, Hopkinson Mark, Betz Janina, Heilig Juliane, Sodhi Jassi, Imhof Thomas, Niehoff Anja, Birk David E, Izu Yayoi, Krüger Marcus, Pitsillides Andrew A, Altmüller Janine, van Osch Gerjo J V M, Straub Volker, Schreiber Gudrun, Paulsson Mats, Koch Manuel, Brachvogel Bent
Department of Pediatrics and Adolescent Medicine, Experimental Neonatology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Institute for Dental Research and Oral Musculoskeletal Biology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
iScience. 2023 Jun 28;26(7):107225. doi: 10.1016/j.isci.2023.107225. eCollection 2023 Jul 21.
Collagen XII, belonging to the fibril-associated collagens, is a homotrimeric secreted extracellular matrix (ECM) protein encoded by the gene. Mutations in the human gene cause an Ehlers-Danlos/myopathy overlap syndrome leading to skeletal abnormalities and muscle weakness. Here, we studied the role of collagen XII in joint pathophysiology by analyzing collagen XII deficient mice and human patients. We found that collagen XII is widely expressed across multiple connective tissue of the developing joint. Lack of collagen XII in mice destabilizes tendons and the femoral trochlear groove to induce patellar subluxation in the patellofemoral joint. These changes are associated with an ECM damage response in tendon and secondary quadriceps muscle degeneration. Moreover, patellar subluxation was also identified as a clinical feature of human patients with collagen XII deficiency. The results provide an explanation for joint hyperlaxity in mice and human patients with collagen XII deficiency.
Ⅻ型胶原蛋白属于原纤维相关胶原蛋白，是一种由该基因编码的同三聚体分泌型细胞外基质（ECM）蛋白。人类该基因的突变会导致埃勒斯-当洛综合征/肌病重叠综合征，从而引发骨骼异常和肌肉无力。在此，我们通过分析Ⅻ型胶原蛋白缺陷小鼠和人类患者，研究了Ⅻ型胶原蛋白在关节病理生理学中的作用。我们发现Ⅻ型胶原蛋白在发育中的关节的多种结缔组织中广泛表达。小鼠体内缺乏Ⅻ型胶原蛋白会使肌腱和股骨滑车沟不稳定，从而在髌股关节中诱发髌骨半脱位。这些变化与肌腱中的细胞外基质损伤反应以及继发性股四头肌变性有关。此外，髌骨半脱位也被确定为Ⅻ型胶原蛋白缺乏的人类患者的临床特征。这些结果为Ⅻ型胶原蛋白缺乏的小鼠和人类患者的关节过度松弛提供了解释。
