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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.

Original publication

DOI

10.1371/journal.pone.0167971

Type

Journal article

Journal

PloS one

Publication Date

01/2016

Volume

11

Addresses

Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Apex building, Liverpool, United Kingdom.

Keywords

Cartilage, Bone and Bones, Growth Plate, Femur, Tibia, Cells, Cultured, Osteoblasts, Animals, Mice, Inbred C57BL, Mice, Inbred CBA, Mice, Transgenic, Humans, Mice, Collagen Type II, Tissue Inhibitor of Metalloproteinase-3, Osteogenesis, Tensile Strength, Male, Promoter Regions, Genetic