Jarkko Koivunen, Antti V. Kemppainen, Mikko A. Finnilä, Riikka Keski-Filppula, Heli Härönen, Hongmin Tu, Henri Pellikka, Anne Heikkinen, Elina Kylmäoja, Raija Sormunen, Ilkka Miinalainen, Simo Saarakkala, Valerio Izzi, Taina Pihlajaniemi, Collagen XIII-derived ectodomain regulates bone angiogenesis and intracortical remodeling, Matrix Biology, Volume 83, 2019, Pages 6-25, ISSN 0945-053X, https://doi.org/10.1016/j.matbio.2019.06.005
Collagen XIII-derived ectodomain regulates bone angiogenesis and intracortical remodeling
|Author:||Koivunen, Jarkko1; Kemppainen, Antti V.1; Finnilä, Mikko A.2;|
1Oulu Center for Cell-Matrix Research and Biocenter Oulu, Faculty of Biochemistry and Molecular Medicine, P.O. Box 5400, FIN-90014, University of Oulu, Oulu, Finland
2Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, P.O. Box 5000, FIN-90014, University of Oulu, Oulu, Finland
3Institute of Cancer Research and Translational Medicine, Department of Anatomy and Cell Biology, Medical Research Center, P.O. Box 5000, FIN-90014, University of Oulu, Oulu, Finland
4Biocenter Oulu, P.O. Box 5000, FIN-90014, University of Oulu, Oulu, Finland
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2019120445661
|Publish Date:|| 2020-06-17
Osteoporosis is the most common degenerative bone disease that occurs when the balance of bone production and resorption is perturbed. Loss of bone mass or alteration in its quality leads to significant weakening of the bones and subsequently to higher fracture risk. Collagen XIII (ColXIII) is a conserved transmembrane protein expressed in many mesenchymal tissues. Here we show that ColXIII is a regulator of bone remodeling niche. In this study, we found that ColXIII expression is significantly upregulated in osteoporotic patients. In view of that, we studied bone homeostasis in ColXIII-overexpressing mice (Col13a1oe) up to 72 weeks of age and observed a cortical bone overgrowth followed by a drastic bone loss, together with increased bone vascularization. Moreover, our results demonstrate that the ColXIII-derived ectodomain enhances angiogenesis through β1-integrins and the JNK pathway. Consequently, these data suggest that ColXIII has a role in age-dependent cortical bone deterioration with possible implications for osteoporosis and fracture risk.
|Pages:||6 - 25|
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
1182 Biochemistry, cell and molecular biology
This work was supported by grants from Biocenter Oulu, the Sigrid Jusélius Foundation, European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement no. 336267 and the Academy of Finland (grants no. 268378, 273571, 294617 and 284605). Part of research infrastructure has been supported by the European Commission Regional Development Fund (decision nr. 538/2010).
|EU Grant Number:||
(336267) 3D-OA-HISTO - Development of 3D Histopathological Grading of Osteoarthritis
|Academy of Finland Grant Number:||
268378 (Academy of Finland Funding decision)
273571 (Academy of Finland Funding decision)
294617 (Academy of Finland Funding decision)
© 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/.