Overexpression of TIMP-3 in chondrocytes produces transient reduction in growth plate length but permanently reduces adult bone quality and quantity
| Autor: | Poulet, Blandine, Liu, Ke, Plumb, Darren, Vo, Phoung, Shah, Mittal, Staines, Katherine, Sampson, Alexandra, Nakamura, Hiroyuki, Nagase, Hideaki, Carriero, Alessandra, Shefelbine, Sandra, Pitsillides, Andrew A., Bou-Gharios, George |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
572 Biochemistry Biomedical Science Research Group Organogenesis Biochemistry Mice Animal Cells Osteogenesis Medicine and Health Sciences Biomechanics Growth Plate Femur Promoter Regions Genetic Cells Cultured Connective Tissue Cells Medicine(all) Agricultural and Biological Sciences(all) Bone and Joint Mechanics Connective Tissue Health Medicine Cellular Types Anatomy Research Article Science Mice Transgenic Osteocytes Bone and Bones Chondrocytes Tensile Strength Animals Humans Bone Collagen Type II Tissue Inhibitor of Metalloproteinase-3 QP Physiology Osteoblasts Bone Development Tibia Biochemistry Genetics and Molecular Biology(all) Biology and Life Sciences Proteins Cell Biology Mice Inbred C57BL Biological Tissue Cartilage Mice Inbred CBA Organism Development Collagens Developmental Biology |
| Zdroj: | PLoS ONE PLoS ONE, Vol 11, Iss 12, p e0167971 (2016) PLoS One |
| ISSN: | 1932-6203 |
| Popis: | Bone development and length relies on the growth plate formation, which is dependent on degradative enzymes such as MMPs. Indeed, deletion of specific members of this enzyme family in mice results in important joint and bone abnormalities, suggesting a role in skeletal development. As such, the control of MMP activity is vital in the complex process of bone formation and growth. We generated a transgenic mouse line to overexpress TIMP3 in mouse chondrocytes using the Col2a1-chondrocyte promoter. This overexpression in cartilage resulted in a transient shortening of growth plate in homozygote mice but bone length was restored at eight weeks of age. However, tibial bone structure and mechanical properties remained compromised. Despite no transgene expression in adult osteoblasts from transgenic mice in vitro, their differentiation capacity was decreased. Neonates, however, did show transgene expression in a subset of bone cells. Our data demonstrate for the first time that transgene function persists in the chondro-osseous lineage continuum and exert influence upon bone quantity and quality. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|