Increased bone formation in mice lacking plasminogen activators
| Autor: | Roger Bouillon, G Carmeliet, Sophie Torrekens, E Van Herck, Vincent Everts, W Tigchelaar-Gutterr, E Daci |
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| Přispěvatelé: | Parodontologie (OUD, ACTA), Cell Biology and Histology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, CCA -Cancer Center Amsterdam |
| Rok vydání: | 2003 |
| Předmět: |
Endocrinology
Diabetes and Metabolism Long bone Bone Matrix Tissue plasminogen activator Mice Osteogenesis medicine Animals Orthopedics and Sports Medicine RNA Messenger Endochondral ossification Mice Knockout Bone growth Osteoblasts biology Ossification Chemistry Plasminogen Osteoblast Organ Size Urokinase-Type Plasminogen Activator Cell biology medicine.anatomical_structure Gene Expression Regulation Biochemistry Tissue Plasminogen Activator Osteocalcin biology.protein medicine.symptom Plasminogen activator Gene Deletion medicine.drug |
| Zdroj: | Journal of Bone and Mineral Research, 18, 1167-1176. Wiley-Blackwell Journal of Bone and Mineral Research, 18, 1167-1176. American Society for Bone and Mineral Research Daci, E, Everts, V, Torrekens, S, van Herck, E, Tigchelaar-Gutter, W, Bouillon, R & Carmeliet, P 2003, ' Increased bone formation in mice lacking plasminogen activators ', Journal of Bone and Mineral Research, vol. 18, pp. 1167-1176 . https://doi.org/10.1359/jbmr.2003.18.7.1167 Journal of bone and mineral research, 18(7), 1167-1176. Wiley-Blackwell |
| ISSN: | 0884-0431 |
| DOI: | 10.1359/jbmr.2003.18.7.1167 |
| Popis: | Plasminogen activators tPA and uPA are involved in tissue remodeling, but their role in bone growth is undefined. Mice lacking tPA and uPA show increased bone formation and bone mass. The noncollagenous components of bone matrix are also increased, probably from defective degradation. This study underlines the importance of controlled bone matrix remodeling for normal endochondral ossification. Introduction: Proteolytic pathways are suggested to play a role in endochondral ossification. To elucidate the involvement of the plasminogen activators tPA and uPA in this process, we characterized the long bone phenotype in mice deficient in both tPA and uPA (tPA / :uPA / ). Materials and Methods: Bones of 2- to 7-day-old tPA / :uPA / and wild-type (WT) mice were studied using bone histomorphometry, electron microscopy analysis, and biochemical assessment of bone matrix components. Cell-mediated degradation of metabolically labeled bone matrix, osteoblast proliferation, and osteoblast differenti- ation, both at the gene and protein level, were studied in vitro using cells derived from both genotypes. Results: Deficiency of the plasminogen activators led to elongation of the bones and to increased bone mass (25% more trabecular bone in the proximal tibial metaphysis), without altering the morphology of the growth plate. In addition, the composition of bone matrix was modified in plasminogen activator deficient mice, because an increased amount of proteoglycans (2), osteocalcin (45%), and fibronectin (36%) was detected. Matrix degradation assays showed that plasminogen activators, by generating plasmin, participate in osteoblast-mediated degradation of the noncollagenous components of bone matrix. In addition, proliferation of primary osteoblasts derived from plasminogen activator-deficient mice was increased by 35%. Finally, osteoblast differentiation and formation of a mineralized bone matrix were enhanced in osteoblast cultures derived from tPA / :uPA / mice. Conclusions: The data presented indicate the importance of the plasminogen system in degradation of the noncollagenous components of bone matrix and suggest that the accumulation of these proteins in bone matrix—as occurs during plasminogen activator deficiency—may in turn stimulate osteoblast function, resulting in increased bone formation. J Bone Miner Res 2003;18:1167-1176 |
| Databáze: | OpenAIRE |
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