Collagen XII as a risk factor for musculoskeletal diseases
Prof. Dr. Manuel Koch
Institute for Experimental Dentistry and Oral Musculoskeletal Biology
Faculty of Medicine, University of Cologne
Joseph-Stelzmann-Str. 52, 50931 Cologne
The collagen family of proteins plays an important role in musculoskeletal homeostasis. The critical functions of collagens are clearly illustrated by a wide spectrum of collagen-related diseases found in humans, e.g., osteogenesis imperfecta, myopathy, and Ehlers-Danlos syndrome. The function of collagen XII was not known until recently. However, since we could show that collagen XII binds to proteins involved in connective tissue diseases, it was no surprise that mutations in collagen XII also cause an Ehlers-Danlos - myopathy overlap syndrome.
In collaboration we could identify several families/patients harboring mutations in the COL12A1 gene. To study the molecular mechanism of this syndrome, collagen XII deficient mice were generated. The mice were born but developed kyphosis and muscle weakness. Initial studies revealed that cortical bones were weaker due to the loss of osteoblast polarity and osteocytes had reduced numbers of cytoplasmic/dendritic processes. Furthermore, muscle weakness was observed, which were not caused by the muscle units themselves since physiological measurements on isolated muscles did not show any difference.
Our present goal is to elucidate the function of collagen XII in the musculoskeletal system.