Licentiate of Medicine Antti Kemppainen
Faculty and research unit
University of Oulu Graduate School, Faculty of Biochemistry and Molecular Medicine, ECM and hypoxia
Field of study
Biochemistry and Molecular Medicine
Date and time of the thesis defence
Place of the thesis defence
Leena Palotie Auditorium 101A, Aapistie 5A, Zoom link: https://oulu.zoom.us/j/69197895335?pwd=VVZIWlFBM3dHaWhKMnBkWTJySVR4Zz09
Topic of the dissertation
Bone tissue and its vasculature in mouse models of collagen XIII
Professor Riku Kiviranta, University of Turku
Professor Taina Pihlajaniemi, University of Oulu
Collagen XIII participates in bone turnover
Collagen XIII is a transmembrane protein that is widely expressed in various tissues of the body. In particular, collagen XIII is expressed in cell-cell and cell-extracellular matrix junctions, neuromuscular junctions and the periosteum. Mutations of the gene encoding collagen XIII cause a subtype of hereditary myasthenic syndrome, in which, in addition to functional neuromuscular disorders and muscle weakness, various developmental disorders of facial and body bones have been described.
Efforts have been made to elucidate the tissue and cellular significance of collagen XIII using a variety of genetically modified mouse lines. Collagen XIII can be enzymatically cleaved from the cell membrane, presenting in the body as cell membrane and extracellular matrix forms. Mice lacking collagen XIII resemble patients with hereditary myasthenic syndrome in their muscle and neuromuscular junction findings. The lack of only the extracellular matrix form also had a significant effect on the development of neuromuscular junctions. The effects of collagen XIII deficiency on bone tissue development in these two mouse models have not yet been elucidated. However, collagen XIII has a significant role in bone, as a significant increase in postnatal bone mass due to excessive bone production has been observed in a mouse model overexpressing collagen XIII.
This dissertation investigated the significance of the lack of different forms of collagen XIII as well as overexpression in bone tissue development and turnover using four genetically modified mouse models. The lack of the extracellular form and both forms of collagen XIII in mice caused a decrease in femoral cortical bone mass with aging without significantly affecting the trabecular bone. Transgenic overexpression of collagen XIII caused a significant decrease in bone mass from the bone marrow cavity surface after the bone mass had increased. The bone tissue of these transgenic mice contained less calcium and more blood vessels than usual, and the bone osteocyte network was underdeveloped. In metatarsal tissue cultures, angiogenesis of the bones overexpressing collagen XIII was accelerated, and differences to the control group disappeared with the addition of a JNK inhibitor or a β1 integrin inhibiting antibody. The effects of collagen XIII overexpression on bone mass were mitigated in integrin α11β1 knockout mice.
Osteoporosis is a skeletal disease in which a decline in bone strength predisposes to fracture. Factors that determine bone strength include bone microstructure, rate of turnover, degree of mineralization and collagen structure. The presented research results show that collagen XIII plays a significant role in bone tissue. Based on the results of the study, collagen XIII is an important component in the lifelong upkeep of bone tissue. The dissertation also discovered a possible cellular mechanism by which the overexpression of collagen XIII affects bone balance. The results also suggest the involvement of integrin α11β1 as a mediator of collagen XIII’s effects.
Last updated: 26.11.2020