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Overexpression of TIMP-3 in chondrocytes produces transient reduction in growth plate length but permanently reduces adult bone quality and quantity

DOI: 10.1371/journal.pone.0167971 DOI Help

Authors: Blandine Poulet (University of Liverpool) , Ke Liu (University of Liverpool) , Darren Plumb (University of Liverpool) , Phoung Vo (Kennedy Institute of Rheumatology) , Mittal Shah (The Royal Veterinary College) , Katherine Staines (Royal Veterinary College) , Alexandra Sampson (The Royal Veterinary College) , Hiroyuki Nakamura (Kennedy Institute of Rheumatology) , Hideaki Nagase (Kennedy Institute of Rheumatology) , Alessandra Carriero (Florida Institute of Technology) , Sandra Shefelbine (Northeastern University) , Andrew A. Pitsillides (The Royal Veterinary College) , George Bou-Gharios (University of Liverpool)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Plos One , VOL 11

State: Published (Approved)
Published: December 2016

Open Access Open Access

Abstract: 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.

Journal Keywords: Osteoblasts; Chondrocytes; Bone development; Cartilage; Growth plate; Osteocytes; Collagens; Tibia

Diamond Keywords: Bone; Enzymes

Subject Areas: Biology and Bio-materials

Instruments: I22-Small angle scattering & Diffraction

Added On: 04/01/2017 16:16


Discipline Tags:

Life Sciences & Biotech

Technical Tags:

Scattering Small Angle X-ray Scattering (SAXS) Wide Angle X-ray Scattering (WAXS)