Expression Patterns of Matrix Metalloproteinases and Vascular Endothelial Growth Factor During Epiphyseal Ossification

Authors

  • Jesús Álvarez,

    1. Departamento de Morfología y Biología Celular, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, Oviedo, Asturias, Spain
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    • These authors contributed equally

  • Lorena Costales,

    1. Departamento de Morfología y Biología Celular, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, Oviedo, Asturias, Spain
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    • These authors contributed equally

  • Rosa Serra,

    1. Deparment of Cell Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA
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  • Milagros Balbín,

    1. Laboratorio de Oncologia Molecular-100PA, Hospital Universitario Central de Astorias, Universidad de Oviedo, Oviedo, Asturias, Spain
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  • José M López PhD

    Corresponding author
    1. Departamento de Morfología y Biología Celular, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, Oviedo, Asturias, Spain
    • Departamento de Morfología y Biología Celular, Facultad de Medicina 8ª planta, 33006 Oviedo, Spain
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  • The authors have no conflict of interest.

Abstract

In situ hybridization studies allowed for the localization of three MMPs and the angiogenic factor VEGF during secondary ossification. MMPs were widely expressed during ossification of the secondary center, whereas expression of VEGF was restricted to later stages.

Introduction: The spatiotemporal expression patterns of the matrix metalloproteinases gelatinase-B (MMP-9), collagenase-3 (MMP-13), and membrane-type 1 metalloproteinase (MMP-14) and the angiogenic peptide vascular endothelial growth factor (VEGF) were studied during development of the proximal epiphysis of the rat tibia.

Materials and Methods: Cell expression was analyzed by in situ hybridization. Studies on osteoclastic activity, matrix mineralization, cell proliferation, and vascular progression were also performed.

Results: MMP-9, MMP-13, and MMP-14 were expressed in discrete perichondrial cells that gave way to sites of intrachondral canal formation. High expression levels for the three MMPs were found at the blind ends of advancing intrachondral canals and at the expanding borders of the marrow space. Signals for MMP-9 and MMP-13 were in close proximity but did not overlap, whereas MMP-14 was expressed in both MMP-9+ and MMP-13+ cells. VEGF was not expressed during formation of intrachondral vascular canals but was observed in hypertrophic chondrocytes during formation of the bone marrow cavity.

Conclusions: Expression of MMPs and VEGF are constant events during development of the secondary ossification center. We propose that MMPs are involved in targeting proteolytic activity during epiphyseal development. VEGF is not expressed during early formation of vascular canals, but it may have a role in the formation of the bone marrow cavity.

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